However, in contrast to cucumber, melon harbors a truncated CmRDR1b gene. In healthy plants, CmRDR1a was expressed, whereas the expression of CmRDR1c1/c2 was not detected. CmRDR1a expression level increased 20-fold upon cucumber mosaic virus (CMV) infection and was not increased in melon plants infected with zucchini yellow mosaic virus (ZYMV), cucumber vein yellowing virus (CVYV) and cucumber green mottle mosaic virus (CGMMV). The expression of CmRDR1c1/c2 genes was induced differentially by infection with viruses from different families: high levels of ~340-, 172- and 115-fold increases were induced by CMV, CVYV and CGMMV, respectively, and relatively low-level increases by potyvirus infection (4- to 6-fold). CMV mutants lacking the viral silencing suppressor 2b protein did not cause increased CmRDR1c/c2 expression; knockout of CmRDR1c1/c2 by CRISPR/Cas9 increased susceptibility to CMV but not to ZYMV. Therefore, it is suggested that the sensitivity of melon to viruses from different families is a result of the loss of function of CmRDR1b. RNA-dependent RNA polymerase 1 (RDR1) plays a crucial defense role against plant viruses by secondary amplification of viral double-stranded RNA in the gene-silencing pathway. In this study, it was found that melon  Melon is an important vegetable crop and melon world production was 28 million tons on 1.1 million hectares in 2020 . EndogenPlant RNA silencing is a cellular defense mechanism that regulates transcription or post-transcriptional gene expression in a sequence-specific manner by small interfering RNA (siRNA) molecules ,6,7. TheIn plants there are six different RDRs; however, RDR1 and RDR6 are the dominant enzymes that amplify single-stranded RNA viruses into aberrant dsRNA, which are digested by the host-encoded Dicer-like (DCL) DCL-4 and DCL-2 proteins into 21–22 nts virus-siRNA duplexes ,10,11,12RDR1, as a single or duplicated gene occurs in all investigated plant species; however, in cucurbits there is a small RDR1 gene family ,15,16. TNicotiana bentamiana, a natural RDR1 mutant (with an insertion of 72 nts) that is highly susceptible to a wide range of viruses [N. bentamiana transformed with RDR1 genes from a number of plant species exhibited increased resistance to virus infection [RDR1 was silenced in species such as Arabidopsis, tomato, tobacco and potato [NtRDR1 in N. bentamiana increased virus susceptibility [RDR1 did not affect virus susceptibility [The association of virus resistance/susceptibility with low/absent RDR1 expression was first described in  viruses . Transgenfection ,27. Corrd potato ,21,28. Htibility  and siletibility . RNA virus infection induced salicylic acid accumulation, which led to RDR1 induction . PretreaRDR1, known to regulate microRNA levels  in rice,RDR1 gene family was based on data from the Cucurbit Genomics Database. In cucumber, four functional CsRDR1 genes were identified  [CsRDR1a and CsRDR1b were expressed, whereas CsRDR1c1 and CsRDR1c2 expression was undetectable. However, virus infection  and cucumber vein yellowing virus (CVYV)) dramatically increased CsRDR1c1 and CsRDR1c2 expression, whereas silencing of CsRDR1c1+2 led to increased virus accumulation [CsRDR1b expression were associated with broad virus resistance [The discovery of the unique cucurbit sRDR1c2) . In healmulation . In addisistance . Cucumis melo) and cucumber (C. sativus) are close relatives and belong to the Cucumis genus (Cucurbitaceae). The genomes of melon and cucumber are highly conserved despite genome duplication in melon (ca. 454 Mbp in 12 chromosome pairs), whereas cucumber has 7 chromosome pairs with a genome size of 367 Mbp. Melon is known to be susceptible to infection by a range of viruses of different families such as zucchini yellow mosaic virus (ZYMV), papaya ringspot virus (PRSV-W), water melon mosaic virus (WMV) and cucumber vein yellowing virus (CVYV) (family Potyviridae), CMV (Bromoviridae) and cucumber green mottle mosaic virus . Classical breeding for virus resistance in melon has proved insufficient due to limited genetic resistance sources.Melon  and the differential gene expression responses of plants infected with different viruses. To help in our understanding of the role of CmRDR1c1/c2 genes in the plant response to viral disease, these genes were knocked out using CRISPR/Cas9 technology.In the present study, we characterized the four melon genes of the Cucumis melo L. cvs. Arava and Vedrantais were used for CmRDR gene mapping and virus susceptibility analyses. In addition, in 10 melon genotypes (listed in Cucurbita pepo L. cv. Zuccini) plants were a source of inocula for PRSV-W, WMV and ZYMV. Cucumber (Cucumis sativus L. cv. Bet Alfa) plants were inocula sources for CMV, CMV-Δ2b, CGMMV and CVYV. Melon seedlings at the cotyledon stage with a small true leaf (about 3–5 days post-emergence) were dusted with carborundum  before mechanical inoculation with virus-bearing sap (ca. 1:10 ratio g tissue/mL H2O) [/mL H2O) . https://melonomics.net (accessed on 28 February 2020))  from eleven plant species (accession numbers in y 2020)) . All othCmRDR1 , CmRDR2, CmRDR6, and cyclophilin genes based on the Melonomics database  using the Dellaporta method  and TRI-database . PCR condatabase  and non-The pRCS binary vector containing Cas9-sgRNA was generated based on 35S:Cas9-AtU6:sgRNA-eIF4E . The sgRAgrobacterium-tumefaciens-mediated transformation according to [A Vedrantais melon genotype was used for rding to  with a nCmRDR1c1 and CmRDR1c2 target regions  sequences [CmRDR1 genes, CmRDR1a, CmRDR1b and the duplicated CmRDR1c1 and CmRDR1c2, were mapped in melon using the Melonomics Database (The equences . Four puDatabase .CmRDR1a and CmRDR1b are close to each other (~15 kbp) on chromosome 10 in a positive and negative orientation, respectively, similar to the situation in cucumber [CmRDR1c1 and CmRDR1c2 are duplicated genes located within ~520 kbp of each other on chromosome 9. The exon/intron arrangement of the CmRDR1a, CmRDR1c1 and CmRDR1c2 genes was similar to that of cucumber, with four exons of about the same sizes (CmRDR1c1 and CmRDR1c2 encoding regions exhibited 95% homology and 98% identity on the protein level (CmRDR1c1 and CmRDR1c2 did not exhibit any sequence similarity (data not shown). CmRDR1a and CmRDR1c exhibited 70% amino acid homology, similar to the level of homology in cucumber [CmRDR1b, located on Chr 10, was missing two regions at the 5′-end in the first exon (a: 515 bp) and part of exon II (b: 1041 bp) compared with the cucumber gene    a. Followectively a. A modeand WMV) . The expfections . CsRDR1c expression [CmRDR1c1 and CmRDR1c2 separately in melon infected with CMV and the CMV-Δ2b mutant. CmRDR1c1 and CmRDR1c2 were each expressed about 10-fold less in CMV-Δ2b infection compared with CMV at 9 and 16 days post inoculation (dpi) (CmRDR1c1 and CmRDR1c2 correlated with the lower level of CMV-Δ2b accumulation and milder symptoms than observed with CMV (CmRDR1c1 and CmRDR1c2 was detected in plant 2b-5 infected with CMV-Δ2b 16 dpi (CmRDR1c1 and CmRDR1c2 expression levels increased in 2b-5 compared with other CMV-Δ2b-infected plants (We have recently shown that the CMV-2b suppressor protein was associated with induction of pression . In lighon (dpi) a,b. The with CMV c. Exceptb 16 dpi d. Sequend plants d.CmRDR genes can complement the loss of CmRDR1b function in melon, we examined the expression levels of CmRDR2, CmRDR6 and CmRDR1a in the susceptible melon cv. Arava in response to different viruses at an early growth stage. The expression levels of CmRDR1a and CmRDR6 decreased ~2-fold and the level of CmRDR2 was unchanged in ZYMV-infected plants at 7 dpi  plants developed similarly to the non-mutant WT control plants  infected with CMV exhibited similar severe symptoms as noted in the WT plants  with similar genome organization (intron/exon) to that of cucumber (Cucumis spp. was homologous to those of other genera (Cucurbita and Citrullus) in the Cucurbitaceae  (RDR1 genes was characterized in barley (HvRDR1a and HvRDR1b) [StRDR1a and StRDRb) [In melon, cucumber . Likewispumpkin) . DuplicaHvRDR1b)  and pota StRDRb) . RDR1 gene family in the five cucurbit species , whereas in cucumber the CmRDR1 gene family was located on chromosome 5 [RDR1 has been characterized as a regulatory region [CmRDR1a, b, c1 and c2 genes may imply differential regulation of each RDR1 gene. The close phylogenetic relationship of the  species , suggestmosome 5 , which mmosome 5 . In plany region ,45,46. TCmRDR1b gene from melon accessions worldwide was truncated (cmrdr1b), and the transcript undetectable due to the two missing regions, compared with the CsRDR1b gene in cucumber [CmRDR1b in melon was mutated in an ancestor during genome duplication and transposon amplification associated with retrotransposon elements in this region [We show here that the cucumber . We thers region .CmRDR1a, b, c1+c2 expression levels were determined in melon. CmRDR1a, which shared the highest homology to RDR1 from other species, was continuously expressed in healthy leaves in cucumber and other hosts [cmrdr1b was not observed in melon  and a tobamovirus (CGMMV)  . Likewisatically , probablatically . HoweverCmRDR1c1 and CmRDR1c2 genes share high sequence similarity and have similar expression levels following virus infection   induced CmRDR1c1+2 expression ~20-fold higher than the potyviruses ZYMV, PRSV and WMV during the infection of cucumber [CmRDR2 and CmRDR6) was induced in melon by CMV infection, but not by potyviruses and tobamovirus, which suggests that the suppressor 2b of CMV may play a role in PAMP-triggered immunity [The duplicated nfection , althougnfection . CMV infeit-Alfa . Howeverd lower) , which m nucleus  and can  nucleus ,48. In aic virus  or via tic virus . Interescucumber . This chcucumber . Notablyimmunity .CmRDR1c1+2 was rapidly induced to a high level by various viruses (cmrdr1c1+2 mutant melon lines were generated to test this role. Mutant lines did not differ in plant growth and fruit development from the WT cultivar. Likewise, ZYMV-infected cmrdr1c1+2 mutant plants showed similar severe symptoms to the WT plants and virus accumulation did not differ between mutant and WT plants. Similarly in potato, reduction of StRDR1 expression level by RNAi did not enhance susceptibility to PVY [CmRDR2 and CmRDR6 expression level were observed between mutant and WT plants. These data suggest that in melon the CmRDR1c1+2 genes were not involved with potyvirus defense in our experimental conditions. However, we cannot rule out that under different conditions of abiotic or biotic stresses these genes may be important in protection against potyviruses. In contrast to potyvirus, cmrdr1c1+2 mutant plants infected with CMV showed slightly greater severity compared with WT plants; CMV accumulation was significantly increased 24 and 32 dpi. In addition, CmRDR1c1+2 were highly expressed in WT plants compared with very low levels of expression in mutant plants, suggesting rapid degradation of aberrant RDR1c1 and c2 transcripts of the nonfunctional proteins [CmRDR1c1 and CmRDR1c2 are unique genes associated with defense against CMV infection specifically, and the virus–host interaction in cucumber between the inducer 2b and RDR1c1+c2 probably also occurs in melon [Expression of  viruses , an impoy to PVY . In addiproteins . These din melon . Such viCsRDR1b resistance gene in cucumber is associated with increased and broad virus resistance [CmRDR1b and repair of this gene using advanced technologies such as CRISPR/Cas9 may significantly improve melon resistance to a range of pathogenic viruses.Melon is a susceptible host to many viruses due to limited genetic resistances. In addition, the virus recovery phenomenon is less common in melon than cucumber. We show that high expression levels of the unique sistance . We, the


Monkeypox is a zoonotic disease that was once endemic in west and central Africa caused by monkeypox virus. However, cases recently have been confirmed in many nonendemic countries outside of Africa. WHO declared the ongoing monkeypox outbreak to be a public health emergency of international concern on July 23, 2022, in the context of the COVID-19 pandemic. The rapidly increasing number of confirmed cases could pose a threat to the international community. Here, we review the epidemiology of monkeypox, monkeypox virus reservoirs, novel transmission patterns, mutations and mechanisms of viral infection, clinical characteristics, laboratory diagnosis and treatment measures. In addition, strategies for the prevention, such as vaccination of smallpox vaccine, is also included. Current epidemiological data indicate that high frequency of human-to-human transmission could lead to further outbreaks, especially among men who have sex with men. The development of antiviral drugs and vaccines against monkeypox virus is urgently needed, despite some therapeutic effects of currently used drugs in the clinic. We provide useful information to improve the understanding of monkeypox virus and give guidance for the government and relative agency to prevent and control the further spread of monkeypox virus. Of these, the vast majority were diagnosed at DRC,54 followed by 6 cases in Central African Republic (CAR),55 2 cases in Cameroon,57 3 cases in Nigeria,59 2 cases in Ivory Coast,60 4 cases in Liberia,58 and 1 case each in Sierra Leone and Gabon.56 In 1990, there have been four cases of suspected monkeypox in Cameroon, one of which has been confirmed.62 In 1996, the DRC experienced a prolonged outbreak of human monkeypox. Initially, a patient was confirmed in February 1996, and until August of that year, a total of 71 suspected monkeypox cases were reported. As of 1999, over 500 patients of monkeypox were reported in the DRC.65 From February to August 2001, a total of 16 cases of monkeypox were identified in the province of Equateur in the DRC.66 Meanwhile, a study conducted by Anne et al.67 in the DRC from 2001 to 2004 examined vesicle fluids and crusted scabs from 136 people suspected of having monkeypox. They found 51 patients of monkeypox.It was in 1970 that the first patient of human monkeypox was diagnosed in the DRC.69 Forty-seven cases, with confirmed (37 patients) and suspected (10 patients) monkeypox were reported, and all people infected by contact with pet prairie dogs (Cynomys spp.).70 The pets were infected after being in close proximity to imported small mammals , tree squirrels (Heliosciurus spp.), Gambian giant rats (Cricetomys spp.), brushtail porcupines (Atherurus spp.), dormice (Graphiurus spp.), and striped mice (Hybomys spp.) from Ghana. According to CDC, laboratory tests using virus isolation and PCR amplification have proved that at least three dormice, two rope squirrels, and one Gambian giant rat were found to be infected by monkeypox. It was noted that no deaths occurred and no human-to-human transmission was observed,68 which was explained by the strain being a West African strain, based on genetic analysis.69 In addition, a study has conducted to evaluate the effects of the route of infection on the clinical illness of human monkeypox and demonstrated that significant symptoms of systemic diseases were more likely to occur in cases exposed to complex exposures than in cases exposed to noninvasive exposures .70 In contrast to Africa, a large number of cases confirmed in this outbreak are adults.71 In 2003, the Republic of Congo (ROC) reported the first outbreak of human monkeypox. It was recorded in this outbreak that 11 patients of monkeypox were confirmed and probable, all of whom were younger than 18 years of age, one death occurred. It is believed that the monkeypox virus has been transmitted from human to human six consecutive times, making it the longest recorded series of consecutive transmissions of monkeypox from one individual to another.72 In Unity State, Sudan, between September and December 2005, ten confirmed and nine possible patients of monkeypox were described in 5 villages .73 Between 2010 and 2018, varying numbers of monkeypox patients were documented in several African countries, including DRC,75 CAR,78 Cameroon,80 Liberia,76 Sierra Leone,81 as well as COA.82 In addition, it was reported in 2017 that Nigeria was experiencing an outbreak. 122 confirmed or possible patients of human monkeypox were reported between September 2017 and September 2018 in 17 states in Nigeria. Six deaths were recorded .85Human monkeypox attracted little attention worldwide until the first outbreak outside Africa occurred in the United States in 2003.88 Singapore,90 Israel,92 United States93). On May 2022, multiple cases of monkeypox were identified in the United Kingdom.2 On 6 May 2022, an individual with travel ties to Nigeria was diagnosed with monkeypox.94 On 12 May, the UK Health Security Agency (UKHSA) in London confirmed two additional cases of monkeypox.95 There is no link between the two of them and they have never traveled to the endemic region. A week later, another four cases were confirmed. Unusually, there was no known contact between these patients and the previous confirmed cases.96 By polymerase chain reaction (PCR) experiment of patient swab samples, the outbreak was caused by the West African clade of monkeypox virus, which is less fatal than the other known monkeypox variant  after infection, with a case lethally rate of only 1%.98Thousands of people around the world have been infected by the monkeypox outbreak in 2022, which followed several years of sporadic cases outside of Africa  declared monkeypox a public health emergency on August 4, 2022 in the United States.120 The monkeypox epidemic in the United States is extremely serious, as of September 6, monkeypox had since spread to every state, with a total of 20,733 cases.122After May 2022, a large number of monkeypox patients were confirmed in non-endemic countries worldwide. This unusual outbreak promoting the WHO to declare monkeypox as an “evolving threat of moderate public health concern” on June 23. Furthermore, the WHO announced that monkeypox outbreaks in many countries and regions constitute a “Public Health Emergency of International Concern” (PHEIC) on July 23, 2022.124 Several researches have conducted to determine the reservoir or natural hosts of monkeypox virus, Khodakevich et al.126 Have reported that antibodies to the virus were found in 2 of 18 squirrels tested. The monkeypox virus was extracted from a diseased squirrel, Funisciurus anerythrus, which was the first report of monkeypox virus being isolated from a wild animal. Other researches have also suggested that squirrels of the genera Funisciurus and Heliosciurus are related to the natural cycle of monkeypox virus in DRC,130 as well as Rodents of the genera Cricetomys, Graphiurus, elephant shrews of the genus Petrodromus.127 In March 2012, monkeypox virus was separated from a wild-living monkey (a sooty mangabey) by Radonic et al.131 Its whole-genome sequence showed that it had significant similarities with monkeypox viruses located in Western Africa. Patrono and colleagues132 described the frequent appearance of monkeypox virus in a wild-living chimpanzees  population from Taï National Park, Ivory Coast. A number of animal species, mostly rodents and non-human primates, have been confirmed to be susceptible to the virus after multiple investigations,134 as listed in Table Monkeypox is a zoonotic disease whose natural reservoir remains unknown.141 Person to person transmission of monkeypox is caused by close contact with a human with monkeypox virus infection, including contact respiratory secretions from those infected individuals, skin lesions or genitals, prolonged face-to-face contact, along with their bedding and clothing144  by aggregating all patients in 70 countries as of July 22 2022. According to initial estimates based on analysis of the first 255 PCR-identified patients of monkeypox in Italy in 2022, the reproduction number among men who have sex with men is 2.43 (95% CI 1.82–3.26).162 Which indicates that the disease has epidemic potential. Meanwhile, the vast majority of monkeypox patients had not recently traveled to the endemic regions of Africa, such as Nigeria, the DRC as well as central and western Africa.163 Human-to-human transmission of this virus is unusually frequent in this outbreak, suggesting close contact is the most likely route of transmission.164According to previous reports, monkeypox virus was not previously been highly contagious. Monkeypox of the CB clade was found to have a lower basic reproduction number (R0) than 1 between 1980 and 1984 in the Democratic Republic of the Congo.177 It is reported that higher proportion of MSM infected is due to accidental entry into the community and then sexual behavior constituting “close contact” rather than sexual transmission of the monkeypox virus itself.178 However, a study of samples from 528 confirmed cases outside endemic areas in Africa between April and June showed that 98% of patients were bisexual men or gay and 95% of those infected were suspected of transmission through sexual activity.179 A prospective cohort study in Spain indicated that 91.7% cases identifying as MSM in 181 monkeypox infection cases.180 Besides, monkeypox virus DNA was detected by PCR in seminal fluid in 29 of the 32 cases.179 On 3 August, In the Monkeypox Surveillance Bulletin published by the ECDC-WHO Regional Office for Europe, 99%  of the cases were males, with 43.4% of MSM cases.181 Meanwhile, using a branching process transmission model, researchers showed that a small minority of people have disproportionately large numbers of partners, which could explain the continued increase in monkeypox patients among MSM population.182 Another research showed a transmission number of 2.43 in the MSM community among Italian cases in May-June 2022.183 According to Endo and colleagues,182 monkeypox’s basic reproductive number (R0) may be significantly higher than 1 over the MSM sexual contact network. Monkeypox virus spread model for assessing outbreak risk in a metropolitan area indicated that if transmission efficiency increases in the higher-risk group like gays and MSMs, broader populations may be affected.184 On the other hand, Bragezzi et al.185 conducted a meta-analysis to show that sexual contact is involved in 91% cases . Notably, a recent study of 21,098 monkeypox cases  revealed that the vast majority were MSM, with a typical rash characteristic.186 Transmission was mainly through close contact during sexual activities. Overall, all these reports suggested that MSM was up to now the most frequently suspected route of transmission.193 Consequently, targeted interventions are needed in communities with a large part of MSM individuals to prevent further transmission. And further research is demanded to determine whether sexual transmission is possible.Another unusual feature is that the large number of cases diagnosed with monkeypox are male, and a considerable part of patients have sex with men (MSM), particularly in Canada, Spain, and the UK, suggesting that sexuality is another forms of close contact, even though monkeypox was not considered a sexually transmitted disease before.195 There are four major elements of the virion: core, lateral bodies, outer membrane, and the outer lipoprotein envelope.196 The central core contains the viral dsDNA and core fibrils. The monkeypox virus genome consists of 197 kb with the central genomic region comprising of 101 kb.17 Both terminal variables regions include a 6379 bp terminal inverted repetition (ITR) with approximately 80 bp long hairpin loop, 70 or 54 bp short tandem repeats and unique ITR sequences NR 1 and NR 2 and the coding region.198 The virus contains about 190 nonoverlapping open reading frames (ORFs),200 four of which are located in the ITR sequence.197 Genes responsible for viral replication, transcription, assembly, and release are conservatively located in the genome’s central region, as they are in all orthopoxviruses.200 While most of the genes expressing virulence and host tropism are found at both ends of the genome. These terminal genes play a role in immune evasion by interfering with signaling, presentation, and recognition of antigens and apoptosis.203Monkeypox virus is a species of double-stranded DNA virus which causes monkeypox in humans and other animals. It belongs to the genus Orthopoxvirus in the family Poxviridae. Among all animal viruses, poxviruses have the largest and most complex DNA genomes.205 However, the 2022 monkeypox virus diverges from the related 2018–2019 viruses by a mean of 50 single-nucleotide polymorphisms (SNPs), considering previous estimates of the substitution rate for orthopoxviruses, this is much higher than expected.206 Such a divergent branch could speed up the evolution of the monkeypox virus. Notably, further examination of the mutational profiles of these SNPs suggested a dramatic mutational bias, with 26  and 15 (nine non-synonymous and 16 synonymous) being GA>AA and TC>TT nucleotide replacements, respectively. Several studies have indicated that mutations observed in viral genome editing may be caused by apolipoprotein B mRNA-editing catalytic polypeptide-like 3 (APOBEC3) enzymes.212 Another phylogenetic analysis indicated that the monkeypox virus‐2022 strains contained 46 new consensus mutations, including 24 nonsynonymous mutations, compared with the monkeypox virus-2018 strain.213 We suspected that the lower mortality and higher transmission of 2022 monkeypox virus than previous monkeypox virus may related to these viral mutations. Although these viruses are under continual adaptation, it is unknown whether these mutations contribute to help the virus evade host immunity. To further understand how these mutations affect viral function, additional research is required.Monkeypox virus has a low frequency of genomic mutations, due to the DNA double-stranded structure, and the 3’–5’ exonuclease activity of its DNA polymerase.196 Poxviruses enter into the host cell may be divided into 3 steps  and mature virions (MVs), both viral particles have different viral surface epitopes.216 Poxviruses enter cells through different mechanisms depending on their infectious forms, mature virion (MV) with single outer membrane, or enveloped virion (EV) with additional membrane and different protein composition.222Unlike other DNA viruses, monkeypox virus replicates in the cytoplasm of the host cell.224 Up to now, many researches have been demonstrated that several vaccinia virus proteins are vital for binding to the cell surface, including D8L,226 A27L,228 A34R,232 A26L224 and H3L.235 It is following viral attachment that the virion binds to the membrane and fuses with the host cell, causing its core to be released into the cell’s cytoplasm. Virion core contains enzymes and factors that initiate transcription. It was proven that L1, F9, A28, A27, L5, H2 were essential viral envelope proteins for cellular entry.243 Virus-encoded multi-subunit DNA-dependent RNA polymerase initiates viral transcription, which is followed by host ribosome-mediated translation of early, intermediate, and late proteins. The intermediate and late stages of viral gene transcription require cooperation with host-derived transcription factors.248 Synthesis of poxvirus DNA occurs in the cytoplasm. A majority of viral particles remain in the cytoplasm as intracellular mature virions (IMVs) and are encased within the protein matrix of scabs. A second envelope  may be acquired by the remaining virions, and they are attached to the cell membrane of their host.249 As cell surface-associated enveloped virions (CEVs), they cause cell-to-cell transmission of the virus, while extracellular enveloped virions (EEVs) contribute to systemic transmission.250Despite not being able to identify specific receptors for poxviruses, many glycosaminoglycans including heparin sulfates and chondroitin, as well as laminin, contribute to their attachment to cells.253 It is crucial to realize that monkeypox and smallpox differ mainly by the occurrence of lymphadenopathy,141 since 90% of monkeypox patients suffer from lymph node enlargement.254 Monkeypox is most commonly confused with chickenpox, caused by varicella-zoster virus (VZV). In terms of their clinical characteristics, these two diseases share a great deal in common. Moreover, several studies have reported that individuals are infected both monkeypox virus and VZV.127The clinical characteristics of monkeypox are quite similar to those of smallpox, but the monkeypox is clinically milder.256 According to Miura’s report, incubation period (18 cases) is estimated to be 8.5 days on average.255 Based on 22 possible (N = 1) and confirmed (N = 21) monkeypox patients reported in the United States through 6, 2022, Charniga and colleagues estimated the incubation time for monkeypox.256 According to their study, the incubation time from exposure to the onset of symptoms was 7.6 days on average. Besides, another research found that among 23 people with known history of exposure, the median incubation period was 7 days (between 3 and 20 days).179The incubation time of monkeypox virus is usually 5–21 days.260  has no prodromal symptoms, and 37% of patients did not have fever as of the time of assessment, despite most patients included typical features.122 And genital rashes were observed in many cases, which was also recently proven in another studies.270 Other recent reports describe similar clinical characteristics.272 Patel and colleagues272 demonstrated that all 197 monkeypox infection cases developed mucocutaneous lesions, typically in the genitals (111 of 197 patients) or the perianal areas, causing rectal pain and penile edema. Moreover, according to a case report from Spain, 78 of 181 persons had lesions in the oral and perioral region and 141 in the anogenital region. The following complications occurred in 70 of the 181 patients: 45 (24.9%) of 181 had a proctitis, 19 (10.5%) tonsillitis, and 6 (3.3%) had a bacterial skin abscess.180 The clinician should remain vigilant for monkeypox-like rashes regardless of whether the rash has disseminated or had a prodrome prior to the rash. Notably, the possibility of some monkeypox virus infections being asymptomatic has been raised by two recent case reports from Europe. It has been shown in several studies that monkeypox could go unobserved when it is propagable, so physicians and persons at high risk should be aware of this fact.273In the United States, a report on the epidemiological and clinical features of monkeypox cases showed 42% of persons  infection among MSM patients with monkeypox.275 Previous reports278 indicated that the case fatality rates (CFR) of monkeypox ranging from 1 to 11%. What’s more, in a systematic review that exclusively evaluated the case fatality rates (CFR) by clades, the overall rate of case fatalities was confirmed to be 8.7%, which was significantly lower for West African clade  than Central African clade .66 Among 1958 patients, some 4% (95% CI 1–9%) of hospitalized patients had fatal outcomes.260 In the current 2022 monkeypox outbreak, it was reported that patients at least sixteen years old always have milder symptoms in the current investigations, with a pooled case fatality rate of 0.03% (1 of 2941 patients).279 Monkeypox is more often fatal in children, which is similar to smallpox.80 As of September 2022, a total of 15 deaths have been documented in this monkeypox global outbreak, in which 9 deaths in locations that have historically recorded monkeypox.Symptoms of monkeypox last 2–4 weeks, and the disease is usually self-limiting. The lethality of monkeypox patients after infection depend on the clade of virus infected, route of infection, patient age, and patients infected with the CA clade of the virus is generally higher than the WA clade.280 Genes commonly used for conventional polymerase chain reaction (PCR) testing include hemagglutinin,281 the acidophilic-type inclusion body gene,283 and the crmB gene.284 Compared with other diagnostic methods, real-time PCR provides high throughput, high sensitivity, and fast results. Several genes have been developed to detect monkeypox virus, such as envelope protein gene (B6R),285 B7R gene,286 DNA polymerase gene E9L,285 complement binding protein C3L,287 DNA-dependent RNA polymerase subunit 18 (RPO18) gene,288 F3L and N3R.289 Meanwhile, recombinase polymerase amplification (RPA) method has been proven to be an alternative to real-time PCR. It was reported that the monkeypox virus-RPA-method was especially sensitive with a limit of detection (LOD) of 16 DNA molecules per microliter by targeting the tumor necrosis factor binding protein gene.290 With different target sites in the viral genome, these tests have varying sensitivities and limits of detection for monkeypox virus.291 According to Li et al.278 real-time PCR assay for generic monkeypox virus has a limit of detection for 0.7 fg (∼3.5 genomes), while monkeypox virus West Africa specific (G2R_WA) assay’s LOD is at 1.7 fg (∼8.2 genome), and monkeypox virus Congo Basin (C3L) assay’s LOD is at 9.46 fg (∼40.4 genomes). As well, Maksyutov et al.292 developed real-time PCR assay that targets viral F3L gene with a LOD of 20 copies per reaction. Several other studies reported LOD for monkeypox virus assays of 6.359 copies/mL,293 20 copies/reaction,286 11–55 fg (50–250 copies of each gene),289 2 fg ,285 0.05 fg (25 copies/assay).294Diagnosis of monkeypox requires a combination of clinical symptoms, epidemiological information, and laboratory tests. According to WHO recommendations, nucleic acid amplification testing (NAAT) has been conducted for monkeypox virus detection.293 which may expand the detection capacity and reduces the detection of time. In the current outbreak, the whole genome sequencing was also used to identify the monkeypox strain.295 What’s more, there are several other DNA-based assays have been investigated for monkeypox virus detection, such as loop-mediated isothermal amplification (LAMP),296 restriction length fragment polymorphism (RFLP),297 as well as recombinase polymerase amplification (RPA).290Recently, a high-throughput molecular testing method for monkeypox virus was established,299 western blot (WB)300 and immunohistochemistry (IHC).301 It is often necessary to use serologic diagnostic procedures to diagnose poxvirus when there is no virological sample. In most cases, ELISA is the most frequently used serologic test. Serological testing of the specific IgM and IgG antibodies are commonly deployed. As soon as the rash appears, IgM antibodies appear and rise approximately 2 weeks before declining and disappearing within 1 year. While IgG antibodies also generate quickly after the rash onset, rise approximately 6 weeks, and lasts for decades.302 However, the specificity is low, due to the immunologic cross-reactivity between monkeypox virus and other othopoxviruses.251 Electron microscopic observation can be used as an auxiliary method to detect monkeypox virus.303 However, due to the laborious and costly sample preparation, it is difficult to be used popularly.Laboratory methods for detecting monkeypox also include enzyme-linked immunosorbent assay (ELISA),308Treatment is suggested for monkeypox virus-infected individuals with severe disease at present or who may be at high risk for developing serious illness , or those with monkeypox virus aberrant infections, including accidental implantation in mouth, eyes, or other anatomical areas where monkeypox virus infection that could pose a special threat . For most patients, treatment is symptomatic and supportive. Despite the fact that monkeypox has no specific treatment, smallpox antiviral drugs such as brincidofovir, tecovirimat, and cidofovir may have effect against monkeypox because of their similar genetics.309 Tecovirimat targets the VP37 protein, inhibits the spread of viruses within the body by preventing them from leaving infected cells,310 as shown in Fig. 312 Several studies have demonstrated that the VP37 protein plays an essential role in encapsulating intracellular mature virus with Golgi-derived membrane to form enveloped virus.317Tecovirimat , a small-molecule inhibitor of virus, is effective against orthopoxviruses both in vitro and in vivo, including vaccinia virus, camelpox virus, cowpox virus, mousepox virus, variola viruses, and monkeypox virus.318 Further, the effectiveness and safety of tecovirimat has been revealed in multiple animal studies.324 Treatment with 10 mg per kilogram of body weight of tecovirimat for 14 days in the monkeypox model could achieve >90% survival.324 In a nonhuman primate (NHP) model, by taking orally once a day, tecovirimat was found to be effective in protecting NHP from monkeypox virus illness, with reduced viral loads, fewer rashes, prolonged survival and significantly reduced mortality in the treatment group compared with the vehicle mongkeys.325 Smith et al.326 assessed the efficacy of tecovirimat against monkeypox virus challenge of 65 times the 50% lethal dose (LD50) in prairie dogs, and found that one hundred percent of animals that received tecovirimat survived challenge, while 75% of infected animals receiving vehicle alone succumbed to infection. Meanwhile, multiple phase 3 clinical trials of tecovirimat have demonstrated its safety and well tolerated  did not cause side effects and that viral shedding and illness lasted shorter time.329 Besides, data collected from 25 cases with diagnosed monkeypox infection had completed a course of tecovirimat therapy revealed all cases tolerated the antiviral medicine well, with minor side effects. The lesions and pain of 10 patients (40%) were completely resolved by day 7 of therapy, and 23 of 25 patients on day 21. The most frequently adverse events of therapy reported including diarrhea in 2 (8%), itching in 2 (8%), nausea in 4 (16%), headache in 5 (20%), and fatigue in 7 patients (28%).308 Moreover, several reports have also documented the efficacy and safety of tecovirimat in the treatment of monkeypox.332 Healthcare providers can now provide tecovirimat treatment to monkeypox patients under an expanded access Investigational New Drug (EA-IND) protocol developed by CDC and FDA. A total of 1001 cases receiving this antiviral drug have been documented, in addition, data was abstracted by the Centers for Disease Control.333In 2018, the FDA approved its first use for treating smallpox after studies showed it was safe in humans and effective in animals with similar viruses.334 A double-blind, randomized controlled study will be conducted by the National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Disease (NIAID) in treating individuals confirmed with monkeypox in adults and children to evaluate the effectiveness and safety of tecovirimat.335 Meanwhile, through the AIDS Clinical Trials Group, NIH/NIAID is conducting a phase 3 double-blind, randomized controlled investigation of tecovirimat in outpatient in the United States settings to treat monkeypox.335 According to the latest report, it is currently underway or planned to conduct several clinical experiments to evaluate tecovirimat’s safety and effectiveness in treating monkeypox patients .337Despite this, more clinical trials are needed to determine whether this antiviral drug is effective and safe for treating monkeypox infections in people.341 CDV is a prodrug, and it must be phosphorylated by enzymes of the cytoplasm after enter the host cells, and into CDV diphosphate (CDV-pp), which has a prolonged half-life.344 CDV-pp inhibits the viral DNA polymerase during DNA replication, as well as inhibits DNA polymerase 3′–5′ exonuclease activity.343Since 1996, Cidofovir  has been approved for clinical use to treat cytomegalovirus (CMV) retinitis in persons with acquired immunodeficiency syndrome (AIDS).350 Between 72 to 96 h post-infection, treatment of mice inoculated with cowpox virus (CV) or vaccinia virus (VV) resulted in significant protection. And when given at least 5 days before infection or 3 days after infection with either VV or CV, a single-dose pretreatment or posttreatment with CDV at 3 to 100 mg/kg was effective.351 Another mouse model demonstrated that it was completely protective against virus-induced cutaneous lesions and against the associated mortality when started on the day of infection or the first post-infection day of topical treatment with cidofovir. In addition, systemic treatment with cidofovir caused lesions to heal and regress.346 The treatment of mice with cidofovir (for two days after 24 h of virus exposure) suppressed viral loads as well as cytokine levels in plasma and tissue, including interleukin (IL)-10, IL-6, IL-3, and IL-2.352 In non-human primate model, researches proved a significant reduction in mortality and cutaneous monkeypox lesions when CDV treatment is initiated 24 h after lethal intratracheal monkeypox virus infection.353Many animal models and experiments in vitro have reported the effectiveness of cidofovir for treatment orthopoxviruses, including vaccinia, mousepox, as well as monkeypox.354 The use of topical CDV was found to be effective in treating molluscum contagiosum (MC) in a 12-year-old boy with Wiskott–Aldrich syndrome.355 Two children with AIDS were also successfully treated with topical 3% cidofovir in a combination vehicle (Dermovan) for recalcitrant MC.356 CDV has also been documented to be effective against cowpox and human vaccinia in additional case reports.359 Despite the lack of clinical evidence to support its use in treating monkeypox, cidofovir is generally thought to be effective. According to the CDC’s guidance, an outbreak of orthopoxviruses, including monkeypox virus, can be treated with this anti-viral medicine.Various studies have shown the effectiveness of CDV against poxvirus. Patients with recalcitrant molluscum contagiosum virus (MCV) treated with intravenous cidofovir exhibited dramatic cleaning of their MCV lesions, and all three cases remain clean of recurrence.360 CDV-pp suppresses the synthesis of viral DNA by inhibiting the DNA polymerase activity of several double-stranded DNA (dsDNA) viruses or by acting as an acyclic nucleotide and binding to the viral DNA strand365  is a lipid conjugate of the acyclic nucleotide phosphonate, cidofovir (CDV). After brincidofovir entry into target cells, a phospholipase enzyme cleaves the lipid ester linkage in brincidofovir, liberating CDV and activated by two sequential phosphorylations, first yield cidofovir monophosphate (CDV-P) and then yield cidofovir diphosphate (CDV-PP).374 to demonstrate its antiviral efficacy against double-stranded DNA viruses including poxviruses such as monkeypox virus and is currently in human clinical investigations for treating other double-stranded DNA viruses . It was found that BCV treatment early in the illness tended to increase survival against a lethal monkeypox virus challenge; the earlier the treatment was initiated, the greater the chance of survival.381 In summary, these models suggest that treating monkeypox patients early with brincidofovir is more likely to have better outcomes.Brincidofovir has under gone numerous animal studies382 In comparison with cidofovir, brincidofovir has higher intracellular levels of the active drug, well oral bioavailability, superior antiadenoviral activity, and no nephrotoxicity.387 The complete resolution in a patient with progressive vaccinia (PV) demonstrated the effectiveness of brincidofovir in combination with other antiviral drugs.388 Recent research, however, indicates brincidofovir is associated with serious adverse effects in monkeypox patients. Over the past three years, three cases have experienced liver toxicity in the United Kingdom.329 Further studies are warranted in humans regarding the efficacy of brincidofovir against monkeypox virus.In 2021, Brincidofovir was licensed by the FDA for treating human smallpox disease in both adults and children. To facilitate the use of brincidofovir for the treatment of monkeypox, the CDC is currently developing an Expanded Access Investigational New Drug.389 Vaccinia immune globulin (VIG) is a sterile solution made up of high titers of IgG antibodies against the vaccinia virus taken from healthy persons who had been previously vaccinated against the live vaccinia virus.390 CDC allows the use of VIG for the treatment of monkeypox in an outbreak. Several studies have reported the patients received VIGIV for the treatment of orthopoxvirus infection.393 Nevertheless, data on VIG’s effectiveness in treating monkeypox virus infection are unavailable. Physicians may consider using it in severe cases. The VIG is also suitable for prophylactic use in persons with severe immunodeficiency in T cell function for whom smallpox vaccination is contraindicated after exposure to monkeypox virus.Vaccinia immune globulin intravenous (VIGIV), a FDA-approved medicine, is applied to treat smallpox vaccination complications such as severe generalized vaccinia, vaccinia infections in people who have skin conditions, eczema vaccinatum, progressive vaccinia and aberrant infections induced by vaccinia virus (excluding isolated keratitis).To prevent getting monkeypox, CDC suggest that people need to avoid close, skin-to-skin contact with someone who has monkeypox-like rashes, avoid contact with objects and materials that a case with monkeypox has used, use hand sanitizers that contain alcohol before eating, touching the face, and wash your hands frequently after using the bathroom.398 smallpox vaccines (vaccinia virus-based) were recommended for use in the current outbreak of monkeypox.405 Epidemiological data on human monkeypox collected in Zaire from 1980 to 1984 revealed that there was a significant difference in attack rates between contacts without a vaccination scar and those who had been vaccinated in the past (7.2% vs. 0.9%).406 Rimoin et al. suggested that monkeypox incidence increased dramatically in the DRC 30 years after smallpox vaccination campaigns ended.407 Furthermore, their data suggested that vaccine-induced immunity lasts a long time as individuals vaccinated against smallpox >25 years ago are still at reduced risk of monkeypox today. As demonstrated by the US monkeypox outbreak of 2003, smallpox vaccination can potentially sustain cross-immune protection against West African monkeypox for decades afterward. Three individuals who had not previously been infected with monkeypox virus and had been vaccinated against smallpox for decades were unaware of their subsequent infection because none of them had any clinical characteristics associated with the monkeypox.298There is no vaccine specifically designed to prevent monkeypox virus infection. Owning to immunological cross protection among orthopoxviruses,160 Second-generation vaccine is ACAM2000, a live attenuated vaccinia vaccine approved in the USA in August 2007 for prevention of smallpox409  vaccinated treated monkeys survived.412 In a prairie dog model, for ACAM2000, the vaccine administered at 1 day postexposure was similarly effective with the vaccine administered at 3 days postexposure, resulting in 50–62% survival, compared with only 25% survival in the unvaccinated group.411 Taken together, ACAM2000 is likely effective at preventing monkeypox; however, due to its potential for replication, it may cause severe side effects, including progressive vaccinia, eczema vaccinatum, and myopericarditis.421 A person with a weak immune system, including someone with HIV, pregnant women, and those who suffer from skin conditions like eczema, are not advised to use it.422Assessment of the protective effect against aerosolized monkeypox virus in cynomolgus macaques revealed that a single immunization with ACAM2000 vaccines were protected completely.423 Unlike ACAM2000, JYNNEOS is a nonreplicating vaccine, which will not lead to the production of live virus. As a smallpox vaccine, JYNNEOS has demonstrated good immunogenicity, safety, and efficacy both in animal models and clinicals.436 It was the only currently FDA-approved vaccinia vaccine for the prevention of monkeypox disease437 , was approved in individuals 18 years of age or older considered to be more susceptible for smallpox or monkeypox infection in US to prevent both smallpox and monkeypox disease in 2019.446 Meanwhile, in its interim guidance for monkeypox vaccines, WHO recommended post-exposure prophylaxis (PEP) ideally within 4 days of the first exposure, pre-exposure prophylaxis (PrEP) is recommended for health workers at risk, clinical laboratory staff performing diagnostic testing, laboratory personnel working with orthopoxviruses, and others at risk under national policy.447 IMAMUNE is approved for immunization against monkeypox and Orthopox virus by the Public Health Agency of Canada (PHAC), and IMVANEX is recommended by the European Medicine Agency (EMA) for monkeypox prevention.449 By July 27, 786,000 more doses are expected to be released that week after the federal government distributed 300,000 doses of vaccine to state and local health authorities and clinics throughout the country. JYNNEOS is manufactured exclusively by Bavarian Nordic, which has a limited production capacity. Recently, due to the vaccine shortage, Bavarian Nordic has expanded its capacity by working with U.S. contract manufacturer to fill smallpox/monkeypox vaccines.450 In addition, a European Union Authorization (EUA) was approved by the FDA for the JYNNEOS vaccine, allowing healthcare providers to administer it intradermally to individuals 18 years of age and older who have been considered to be more susceptible for monkeypox infection.451 Individuals vaccinated intradermally were less vaccinated (by one-fifth) than those vaccinated subcutaneously (SC). The total dose available for use could increase by five-fold as a result. A study with lower intradermal doses of MVA was found to be immunologically noninferior to the standard subcutaneous dose (NCT00914732).452As a result of the outbreak of monkeypox in 2022, several countries, including the United States, Spain, Germany and the United Kingdom, have announced they are buying vaccines and/or releasing vaccines them from national stockpiles to combat the epidemic. JYNNEOS is being used by the US for pre-exposure vaccination of people who are at risk of occupational exposure to orthopoxviruses according to CDC announcements made in May 2022.453 This high attenuation resulted from a single nucleotide deletion mutation in the B5R viral gene, resulting in a truncated membrane protein B5, which is one of the most immunogenic proteins.456 Several animal model challenge studies of safety and efficacy of LC16m8 have been conducted in mouse,461 rabbit,460 and nonhuman primates.463 Both the intranasal and subcutaneous inoculation models showed no symptoms of monkeypox after immunization with LC16m8.462 A single vaccination of non-human primate model revealed that LC16m8 exhibited long-lasting protection against monkeypox virus, evidence from the reduction in viremia and the IgG antibody response.464 Notably, another nonhuman primate model revealed that for immunocompromised individuals, LC16m8 is a safer and more effective alternative to ACAM2000 and Dryvax (first-generation vaccines).463 LC16m8 was shown to produce neutralizing antibodies for vaccinia, monkeypox, and variola major, as well as broad T cell responses in a phase I/II clinical trial.465 In addition, various immunogenic studies in human have confirmed a good safety profile about LC16m8.472 In summary, these results reveal that LC16m8 may be effective for preventing people against monkeypox. Japanese authorities expanded the range of indications for this vaccine to include protection against monkeypox in August 2022.473In 1975, the other smallpox vaccine, LC16m8, was licensed for active immunization against smallpox in Japan. This vaccine is derived from the Lister (Elstree) strain of vaccinia and is a live, replicating, attenuated 3rd generation vaccine.Monkeypox, COVID-19, and polio are among the three emergencies that WHO has declared worldwide at the moment. Monkeypox is now an international problem after previously being endemic to Africa. Until September 2022, more than 56000 patients have been diagnosed in the monkeypox 2022 outbreak. Monkeypox infection patients are rapidly increasing around the world, it is likely to be caused by a combination of natural and human factors. On the other hand, there has been an increase in human–wildlife contact due to climate change, deforestation, and the Ukrainian–Russian war, among other factors. In addition, it is still possible that monkeypox virus will become more prevalent due to the cessation of smallpox vaccination with vaccinia vaccine in 1980. Currently, in spite of the fact that mass vaccination is not recommended or achievable, individuals manage monkeypox may though vaccine , anti-viral medicines, as well as isolate or quarantine of the patients and any contacts with the patients.272 This novel transmission pattern was suspected during 2017 outbreak of human monkeypox in Nigeria, but was not proven.474 Meanwhile, MSM population has higher risk on other disease through sexual transmission, such as HIV. In Ogoina and colleagues’ study,475 it was reported that monkeypox patients in Nigeria who were HIV-positive had longer-lasting illness, and larger lesions, and a higher percentage of and genital ulcers and secondary bacterial skin infections. By contrast, Tarin-Vicente and his colleagues180 reported that there was no difference between HIV-positive patients and the rest of the population in terms of severity or progression of the disease. Therefore, more investigations are needed to understand the effectiveness of anti-viral treatment among individuals infected with both HIV and human monkeypox virus. Besides, in order to reduce monkeypox transmission within MSM groups, public health efforts must deal with challenges including homophobia, stigma, and discrimination.Particularly, there are large number of patients have been confirmed in MSM population in this 2022 outbreak and has been related to unanticipated anal and genital lesions, suggesting the monkeypox virus may be spreading via sexual transmission.476 Meanwhile, the U.S. Patent and Trademark Office (USPTO) has addressed a patent to the Tonix Pharmaceuticals company for its vaccine candidate namely TNX-801, which was designed to protect against smallpox and monkeypox.477 TNX-801 is a novel, horsepox-based live virus vaccine based on synthesized horsepox (sHPXV). Effectiveness and safety have been demonstrated both in mouse models previously.478 In addition, TNX-801 vaccination protects macaques from monkeypox challenge, no lesions were seen in all monkeys.479 The monkeypox virion membrane surface-binding protein E8L is vital for virus attachment to host cells, which may be also used to explore new vaccine against monkeypox.480 Importantly, knowledge of the immunological response and mechanism of monkeypox virus infection would be critical, providing new ideas for vaccine development. Identification of the genes responsible for the host-range defect of virus may engineer more effective and safe vaccines, such as C16L/B22R, C16L (MVA genome).481 For severely immunocompromised individuals, valid vaccination strategies that bypass CD4 negative cell help are needed to protect against virus.482Given the current global monkeypox epidemic, a race to create monkeypox -specific vaccines may occur like COVID-19 Fig. . Moderna11 people should raise awareness and build diagnostic capacity for the monkeypox epidemic in order to limit further spread of the virus. We should improve understanding and clinical management of monkeypox, as well as infection prevention and control skills, especially among public health personnel. At the same time, stigma and discrimination within the MSM community should be properly addressed and equitable access to treatment and vaccines should be ensured. Finally, we should initiate a global collaboration to conduct clinical investigations to test the efficacy and safety of monkeypox vaccines as well as antiviral drugs.Global public health has been severely tested by the COVID-19 pandemic in the past two years. Confirmed cases of monkeypox are increasing rapidly worldwide especially in the US, which may have a negative impact on the global economy. With monkeypox being announced a public health emergency of international concern by WHO,


Ganoderma lucidum and Cordyceps sinensis are widely used all over the world, and they can enhance human immunity and direct anti-virus activities and other aspects to play an antiviral role. Medicinal fungi are used as foods or as food supplements. In this review, the species of medicinal fungi with antiviral activity in recent decades and the mechanism of antiviral components were reviewed from the perspectives of human, animal, and plant viruses to provide a comprehensive theory based on better clinical utilization of medicinal fungi as antiviral agents.Pandemics from various viruses make natural organisms face challenges over and over again. Therefore, new antiviral drugs urgently need to be found to solve this problem. However, drug research and development is a very difficult task, and finding new antiviral compounds is desirable. A range of medicinal fungi such as  In today’s world, the outbreak of many infectious diseases has posed a serious threat to human life and health. As early as thousands of years ago, the outbreak of smallpox had caused tens of thousands of human deaths . The outGanoderma lucidum to the American Herbal Pharmacopoeia and Treatment Program [Medicinal fungi are widely used all over the world. In Pakistan, nearly 23 species of medicinal fungi are used to treat colds, cough, influenza, asthma and other diseases . The Uni Program . The med Program . It can  Program . Its ant Program ,10,11. BThere has been a good summary of antiviral polysaccharides from medicinal fungi . In thisMedicinal fungi can fight viruses in a variety of ways . At presNovel coronavirus disease 2019 (COVID-19) is an enveloped positive-stranded single-stranded RNA coronavirus of the betacoronaviridae family . The higGanoderma lucidum were tested. It was found that the L-fucose–containing polysaccharides fraction 3 (RF3) had excellent antiviral activity (2 μg/mL) and was still effective at 1280 times dilution without cytotoxicity [Ganoderma lucidum, Grifola frondosa, Agrocybe species, Auricularia auricula, Hericium erinaceus, Hypsizygus marmoreus, Pleurotus cystidiosus, P. eryngii, P. flabellatus, P. florida, P. sajor-caju, Schizophyllum commune, Tricholoma giganteum, and Volvariella volvaceae. In addition to peptides and proteins, ACE inhibitory triterpenes were extracted from Ganoderma lucidum. The ACE inhibition of these mushrooms can indirectly restore the ACE/ACE2 ratio, thus providing COVID-19’s treatment effect [Antrodia cinnamomea, has ACE2 inhibitory effect and can be used as new anti-ACE2 agents to combat SARS-CoV-2 infection [In a cell-based anti-SARS-CoV-2 test, several polysaccharides containing L-fucose isolated and characterized from t effect . Antcinsnfection .Lentinus edodes have various biological activities and may play a positive role in the treatment of COVID-19. AHCC, a polysaccharide extracted from Lentinus edodes mycelia, has therapeutic effects on different types of viral infectious diseases, such as West Nile virus, influenza virus, hepatitis virus, and human papillomavirus, which indicates that regulating the immune system plays a theoretical role in protecting the host from a respiratory infection. Although AHCC has never been tested against human coronavirus, it is supposed to be a potential substance for treating COVID-19 [Lentinus edodes has the potential to treat lung injury and significantly reduce the level of inflammation in the lungs. CL extract can reduce early apoptosis induced by oxidative stress, while IHL extract can inhibit late apoptosis. These two polysaccharides can alleviate the damage caused by virus infection in the form of nutritional and health products in the future [Cordyceps sinensis, and novel coronavirus-related target protein by molecular dynamics simulation, and found that cordycepin had strong binding force with RBD domain of novel coronavirus spike protein. This suggests that cordycepin may be used as a pan coronavirus fusion inhibitor targeting spike proteins to limit the entry of the virus into the body [The polysaccharides contained in COVID-19 . Anothere future . In recethe body .IV belong to Orthomyxoviridae and have segmented single-stranded RNA genomes, which are usually divided into A, B, and C types. Influenza A virus is the most popular virus in the world . The outGrifola frondosa. Adding ME and MFs to infected cells can reduce the yield of the virus. This may be related to the fact that the extracts induce the production of cytokines such as TNF-α, which can inhibit virus growth in vitro [Phellinus igniarius also showed good antiviral activity. Two compounds, the phelligridins E and G were isolated from the methanol extract of Phellinus igniarius fruiting bodies, which showed neuraminidase inhibitory activity against recombinant H1N1, H3N2, and H5N1 in a dose-dependent manner [Phellinus igniarius aqueous extract PIW shows that it has inhibitory activity on 2009 pandemic H1N1, human H3N2, avian H9N2, and oseltamivir-resistant H1N1 viruses, and its mechanism may be related to interfering with the early replication process of the virus [Lentinus edodes mycelium in vivo and in vitro was determined. The results showed that LEM could inhibit the growth of influenza virus in vitro and play a role in the early stage when the virus entered the host cell. In vivo experiments showed that LEM could activate the immune response and inhibit virus infection through the type I IFN pathway [Obi et al., obtained extract ME, MFs  from the fruiting bodies of in vitro . The comt manner . An in v pathway .Cryptoporus volvatus, could inhibit the replication of the influenza virus and reduce the RNA level of the influenza virus [Cryptoporus volvatus fruiting body is also effective against H1N1 infection. The results showed that it could reduce the level of virus in cells, which may be related to the targeted inhibition of virus entry into cells by its water extract. In animal studies, the extract can completely protect mice from virus infection at high doses [A compound Cryptoporic acid E (CAE), extracted from za virus . The watgh doses .Cordyceps militaris also has a good curative effect against H1N1 infection. An acidic polysaccharide APS was isolated from Cordyceps militaris cultured in germinated soybean. The experimental study in vivo showed that APS could significantly reduce the titer of the virus in the lungs of mice, enhance the immune level and reduce the mortality after intranasal administration [Cordyceps militaris extract was tested against H1N1 virus in DBA/2 mice. The results showed that the extract could reduce the mortality of mice infected with H1N1, increase the levels of cytokines such as TNF-α and IFN-γ, and activate the immune system by promoting the expression of IL-12 [Auuriporia aurea, Flammulina velutipes, Fomes fomentarius, Ganoderma lucidum, Lentinus edodes, Lyophyllum shimeji, Pleurotus eryngii, Pleurotus ostreatus, Schizophyllum commune, and Trametes versicolor, studies have shown that 10 kinds of medicinal mushrooms all showed inhibitory effect on H1N1. T. versicolor has the strongest antiviral effect, and the treatment index is 324.67 [stration . Furtherof IL-12 . Meanwhis 324.67 .Cordyceps sinensis, can reduce the level of inflammation caused by infection with H1N1 and reduce the secretion of inflammatory factors in cells. The anti-inflammatory effect is achieved by regulating the innate immune signal pathway activated by TLR-3-, RIG-I- and type I interferon [Poria cocos. PCP-II combined with H1N1 vaccine could significantly enhance the antibody level, promote the proliferation of B lymphocytes and enhance the humoral immunity produced by the vaccine [Poria cocos, ginger, and dried tangerine peel, after oral administration of MPs and injection of vaccine in mice. It significantly improved the ability of mice to resist viruses, reduced lung injury, and enhanced the level of cellular immunity and humoral immunity [Some medicinal fungi have a good performance in indirectly fighting H1N1. DDEA, a fatty acid in terferon . A new p vaccine . Mixed pimmunity . The antimmunity .EV71, a single-stranded RNA virus of about 7500 nucleotides, belongs to the Enterovirus genus of the Picornaviridae family . EV71 viGrifola frondosa mycelia. The results of cell experiments in vitro showed that GFP1 inhibited the cytopathic effect (CPE) induced by EV71 in a dose-dependent manner. GFP1 inhibited the synthesis of EV71 virus RNA in Vero cells in a dose-dependent manner. The expression of EV71 virus polyprotein was analyzed by western blot. The results showed that GFP1 inhibited the expression of viral VP1 in EV71 infected cells and reduced the apoptosis induced by the EV71 virus by reducing the level of caspase-3 activation [Ganoderma lucidum. In vivo, it was found that the combination of EV-A71 mucosal vaccine and PS-G could activate the immune response and enhance the potential immune cell response to combat virus infection [Ganoderma lucidum also showed inhibit effect on EV71. It was found that GLTA and GLTB had antiviral activity against EV71 virus infection and had no cytotoxicity. The results of molecular docking and PCR show that these two anti-EV71 compounds may block the uncoating process in EV71 infection, thus inhibiting virus infection [A new heteropolysaccharide GFP1 was extracted and purified from tivation . In anotnfection . Two trinfection .In the early 1980s, human immunodeficiency virus type 1 (HIV-1) retrovirus was identified as the pathogen of acquired immunodeficiency syndrome (AIDS) . The genCordyceps sinensis fruiting bodies. The protein has obvious inhibitory activity on HIV-1 reverse transcriptase. The IC50 value is 8.2 × 10−3 μM [Cordyceps sinensis in vitro. The results showed that the five kinds of water extracts had a dose-dependent inhibitory effect on the HIV-1 virus. Further studies showed that their antiviral effect may be related to the activity of HIV-1 reverse transcriptase [Cordyceps militaris. By using the screening system, L3a and L3b showed a high inhibitory effect on HIV-1 reverse transcriptase [Cordyceps militaris which could inhibit the activity of HIV-1 reverse transcriptase with an IC50 value of 10 μM [A novel serine protease cordysobin was purified from the  10−3 μM . The antcriptase . Jiang ecriptase . In anotof 10 μM .Pleurotus citrinopileatus. The lectin had an inhibitory effect on HIV-1 reverse transcriptase with an IC50 of 0.93 μM [Hypsizigus marmoreus and Flammulina velutipes fruiting bodies. Both have HIV-1 reverse transcriptase inhibitory activity [Schizophyllum commune fruiting bodies, both of which could inhibit the activity of HIV-1 reverse transcriptase. The IC50 is 1.8 and 65 mM respectively [Li et al., isolated a lectin from  0.93 μM . In addiactivity ,39. Theyectively ,41.Ganoderma lucidum and Ganoderma lucidum has antler-like fruiting bodies. It was found that both crude extracts could inhibit the attachment of human immunodeficiency virus (HIV-1) glycoprotein 120 (gp120) to cell cluster differentiation 4 (CD4), and AGCs had a higher inhibitory effect on HIV-1 gp120 than NGCs [Ganoderma lucidum. A molecular docking study shows that ganoderic acid B has a good docking effect with HIV-1 protease. HIV-1 protease is a suitable target for ganoderic acid B in general. There is great potential for AIDS treatment based on this compound [Ganoderma lucidum, ganoderic acid β, lucidumol B, ganodermanondiol, ganodermanontriol, and ganolucidic acid A, can inhibit the activity of HIV-1 reverse transcriptase with IC50 value of 20, 50, 90, 70 and 70 μM [Ganoderma lucidum fruiting bodies were found to have anti-HIV-1 activity with an inhibition concentration of 7.8 μg/mL. And ganoderic acid B, ganoderiol B, ganoderic acid C1, 3b-5a-dihydroxy-6b-methoxyergosta-7,22-diene, ganoderic acid a, ganoderic acid H, and ganoderiol A can inhibit HIV-1 reverse transcriptase activity with a 50% inhibitory concentration of 0.17–23 mM [Two kinds of crude extracts NGCs and AGCs from han NGCs . Not onlcompound . Five land 70 μM . Ganoder17–23 mM .Coriolus versicolor could inhibit the activity of HIV-1 reverse transcriptase with an IC50 of 6.25 μg/mL. Inhibition of the interaction between HIV-lgp120 and fixed CD4 receptor IC50 is 1.5 μM [Lentinus edodes, a protein Lentin and a laccase with a molecular weight of 67 kDa were isolated from the fruiting bodies of Lentinus edodes and had inhibitory activity against HIV-1 reverse transcriptase with IC50 values of 7.5 μM and 1.5 μM respectively [Lentinus edodes, EPS4 completely inhibited the cytopathic effect induced by HIV-l when the concentration was more than 10 μg/mL. The water extracts E-P-LEM and LEM can block the cytopathic effect and the expression of specific antigens induced by HIV [Furthermore, a polysaccharide peptide(PSP)extracted from s 1.5 μM . Furthers 1.5 μM . In the ectively ,49. In ad by HIV .HPV is a DNA virus with a double-stranded, closed, circular genome and an unenveloped icosahedral capsid of about 8 kb. HPV infection can lead to a variety of cancers, including cervical cancer, penile cancer, anal cancer, vaginal cancer, vulvar cancer, and oropharyngeal cancer . HPV vacTrametes versicolor and Ganoderma lucidum fruiting bodies powder were put into capsules for oral HPV patients, and 87.8% of the patients were cured after treatment. This confirmed the curative effect of the two kinds of fungi and laid the foundation for further research [Trametes versicolor for 12 days significantly improved the composition of vaginal microbial communities, helping to improve the state of cervical epithelium and vaginal health [In a clinical trial, research . In a prl health . Anotherl health .DENV is an arbovirus that mainly relies on Aedes aegypti mosquitoes as a vector to transmit to humans. It has four different serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. Among them, DENV-2 is the most widely spread ,121. DenBeauveria bassiana spores can significantly inhibit the replication of the dengue virus in the midgut of mosquitoes, which is partly related to the immune activation of effector genes controlled by Toll and JAK-STAT pathways [Lignosus rhinocerotis, Pleurotus giganteus, Hericium erinaceus, Schizophyllum commune, and Ganoderma lucidium were extracted with hot aqueous and ethanol, and then extracted with n-hexane, ethyl acetate and water in turn. The anti-dengue virus activity of the extract was evaluated by a plaque reduction test. The results showed that hot aqueous extracts and aqueous soluble extracts of L. rhinocertis, P. giganteus, H. erinaceus, and S. commune had the least toxicity to Vero cells and showed very significant anti-DENV-2 activity [G. lucidium, S. commune, P. giganteus, and aqueous soluble extracts of L. rhinocerotis successfully inhibited the production of cytokines in monocytes infected by dengue fever [The treatment of Aedes aegypti mosquitoes with pathways . Panya epathways . In anotactivity . The theue fever .Ganoderma lucidum extract on DENV NS2B-NS3 protease was determined in two other studies. The results showed that the inhibition rate of aqueous extract on DENV2 NS2B-NS3 protease was 84.6 ± 0.7%. The main component of the extract was hesperidin by LC-MS. It was proved by molecular docking and density functional theory analysis that hesperidin was an efficient inhibitor of NS2B-NS3 protease [Ganoderma lucidum on DENVNS2B-NS3 protease by molecular docking and obtained 22 kinds of triterpenoids such as Ganodermanontriol. Then the activity of the obtained components was evaluated in vitro, and the virus infection experiment in vitro showed that Ganodermanontriol was a potential bioactive triterpene [The inhibitory activity of protease . Bharadwiterpene .At present, five kinds of hepatitis viruses are prevalent in the world. There is hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV). Except HBV is a DNA virus, all other viruses are RNA viruses. Hepatitis B and C caused by hepatitis virus are the two types with the highest mortality. If chronic hepatitis caused by virus infection cannot be treated in time, it will lead to very serious liver cancer.Cordyceps sinensis extract can reduce the apoptosis of renal tubular epithelial cells induced by HBX protein caused by hepatitis B virus infection. The mechanism is to inhibit the apoptosis of HK-2 cells enhanced by HBX by inhibiting the PI3K/Akt/Bcl-2 pathway [Grifola frondosa by Gu et al., has an inhibitory effect on HBV, and has a synergistic effect with human interferon α-2b in cell experiments. The antiviral mechanism of GF-D may be that it directly interferes with HBV replication at the level of DNA polymerase [Polyporus umbellatus polysaccharides (PUPS) alone or in combination with interferon and other drugs can treat hepatitis caused by HBV [Corbrin capsule prepared from  pathway . The GF-lymerase . In anotd by HBV .Schizophyllum commune can regulate the cellular and humoral immune response of nucleocapsid antigen in patients with chronic hepatitis B and improve the level of antibody [Ganoderma lucidum and the aqueous extract of Radix Sophorae flavescentis co-fermented broth can significantly enhance the anti-hepatitis B virus activity in vitro and enhance the hepatoprotective effect of the body to reduce liver injury compared with the simple mixture of these two ingredients [Moreover, a polysaccharide sizofiran (SPG) isolated from antibody . Li et aredients . Ganoderredients . Zhao etredients .Lentinula edodes mycelia solid culture extract (MSCE) and its main active component low-molecular-weight lignin (LM-lignin) could inhibit the entry of HCV pseudovirus (HCVpv) into cells, and LM-lignin inhibited HCVpv entry at a concentration lower than MSCE [Cordyceps militaris (CM) capsule can inhibit HCV RNA replication in vitro. Further study showed that cordycepin is the main activity component of CM anti-HCV. The effect of cordycepin is related to its inhibition of NS5B polymerase activity [Matsuhisa’s team found that han MSCE . A kind activity .HV is a kind of virus with an envelope and double-stranded DNA genome. HV can be divided into three types: α herpesvirus, β herpesvirus, and γ herpesvirus. Herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) are two popular viruses, and they both belong to the α herpes virus. HSV-1 mainly causes oral and facial infections, while HSV-2 is associated with genital herpes. Epstein-Barr virus (EBV) belongs to γ herpesvirus. Infection of EBV may lead to nasopharyngeal carcinoma (NPC) ,124.Grifola frondosa protein GFAHP can inhibit HSV-1 replication in vitro. The IC50 value is 4.1 μg/mL and the therapeutic index is more than 29.3. In vivo experiments show that GFAHP can alleviate the inflammatory response of mice and reduce the production of virus in vivo [Lentinus edodes mycelia extract JLS-S001 also can significantly inhibit the infection of HSV-1 to cells. This may be related to the fact that JLS-S001 blocks HSV-I replication at the later stage of the virus replication cycle [Ganoderma lucidum. It has antiviral activity against both HSV-1 and HSV-2. The EC50 of APBP to HSV-1 and HSV-2 was 300 and 440 mg/mL. The antiviral activity of APBP may be mainly due to the inhibition of HSV attachment and penetration to Vero cells [A novel  in vivo . A Lention cycle . In anotro cells . Furtherro cells . The resro cells .Ganoderma lucidum. The antiviral experiment in vitro showed that GLhw, GLMe-1, GLMe-2, GLMe-4, and GLMe-7 could significantly inhibit the cytopathic effect of HSV [Ganoderma lucidum, can improve the symptoms of patients with genital and lip herpes and shorten the recovery time of patients [Fomes fomentarius, Phellinus igniarius, and Porodaedalea pini showed strong anti-herpes activity [Pleurotus ostreatus, Fomes fomentarius, Auriporia aurea, and Trametes versicolor had an inhibitory effect on the virus. The highest treatment index of T. versicolor was 324.67 [In addition, the crude extracts of various medicinal fungi also showed anti-HSV activity. Two kinds of water-soluble extracts, GLhw and GLlw, and eight kinds of methanol-soluble extracts, GLMe-1-8, were extracted from t of HSV . WTTCGE,patients . Based oactivity . The mycs 324.67 .Ganoderma lucidum may be used as a potential EBV antigen inhibitor. Iwatsuki et al., studied the inhibitory effect of 17 terpenoids on EB virus early antigen (EBV-EA). The results showed that 16 compounds showed strong inhibitory effects on EBV-EA induction [Cordycepin can inhibit virus infection by affecting the synthesis of virus protein by acting on the gene of EBV, and resist the proliferation of tumor cells caused by EBV infection, and has certain anti-tumor activity . Terpenonduction . Zheng fnduction .RSV is a single-stranded RNA virus, which mainly infects infants with weak immunity and can cause acute lower respiratory tract infection . Since RFlammulina velutipes. In vivo experiments showed that oral administration of FIP-fve could significantly reduce the viral titers of RSV and the level of mRNA in the lungs of mice and reduce the secretion of IL-6. FIP-fve may inhibit RSV replication and RSV-induced inflammation by reducing NF-κB translocation [An immunomodulatory protein FIP-fve was isolated from location .Poliovirus is classified as an enterovirus within the Picornaviridae. The virus genome is a single-stranded (+)-stranded RNA with a length of about 7500 nucleotides . PV usuaLentinus edodes. The results showed that the three extracts showed antiviral activity and mainly played an inhibitory role in the early stage of virus infection [In a study, anti-PV experiments were carried out on aqueous extract AqE, ethanol extract EtOHE and lentinan LeP of nfection .RV is an RNA virus. Rabies caused by RV infection is a fatal and incurable encephalomyelitis. It can kill tens of thousands of people worldwide every year. RV is usually parasitic in many wild animals and can be transmitted through damaged skin and mucosa . At presPoria cocos can be used as a good adjuvant for the rabies vaccine. PCP-II can enhance the level of rabies-specific humoral immunity and cellular immune response and improve the protective effect of vaccines [A polysaccharide PCP-II isolated from vaccines .MARV first appeared in 1967 and was first found in African green monkeys. MARV is one of the deadliest human pathogens in the world. MARV and Ebola virus (EBOV) belong to the filamentous family. The infection will cause high fever, diarrhea, vomiting, and other symptoms, and the mortality rate is very high. There is no effective drug for treatment at present .Poria cocos polysaccharide PCP-II was combined with MARV VLP, the PCP-II group significantly enhanced the specific antibody response and neutralization antibody titer of MARV VLP and improved the immune level of mice [The Gai team successfully constructed a MARV virus-like particle (VLP). When  of mice . The pro of mice .Cordyceps sinensis extract has a therapeutic effect on hepatitis B virus infection. A kind of Cordyceps militaris capsule can affect the replication of HCV. In clinical studies, capsules containing Trametes versicolor and Ganoderma lucidum fruiting body powder have therapeutic effects on patients with oral HPV. Vaginal gel based on Ganoderma lucidum can significantly improve the clinical symptoms of HPV positive patients. Polyporus umbellatus polysaccharides (PUPS) can treat hepatitis caused by HBV. Schizophyllum commune polysaccharide sizofiran (SPG) can improve the antibody level of patients with chronic hepatitis B. WTTCGE, an herbal mixture containing Ganoderma lucidum, can significantly improve the clinical symptoms of patients with herpes.As far as medicinal fungi against human viruses are concerned, many substances with therapeutic, with antiviral effects or substances that cause some other antiviral effects have entered clinical research and commercial production. CL, a commercial lentinan with the potential to treat lung injury, is expected to be used as a health food to regulate lung injury caused by viral infection. The listed drug Corbrin capsule containing IHNV is the pathogen of infectious hematopoietic necrosis (IHN), which mainly causes the infection of many salmon species. It seriously affects the aquaculture industry . A lentiMDRV has high pathogenicity and can infect ducks, chickens, and other poultry. After infection, poultry will have watery diarrhea, leg weakness, and other symptoms. MDRV has had a serious impact on the poultry industry .Hericium Erinaceus can effectively relieve the clinical symptoms and reduce the mortality of diseased Muscovy duck. Further studies have shown that HEP can enhance the defense function of the intestinal mucosal immune system, improve the number of intestinal mucosal immune-related cells, and improve the secretion of intestinal sIgA, IFN-γ, and IL-4 to prevent and treat MDRV infection [Polysaccharide HEP extracted from the fruiting bodies of nfection . The tranfection . HEP cannfection .Schizophyllum commune. In the shrimp feeding experiment, BG was added to the feed of shrimp infected with WSSV. Compared with the control group, BG could enhance the immune level and improve the survival rate of shrimp [WSSV is the cause of white spot disease (WSD), which mainly infects shrimp and many other crustaceans. The mortality rate is as high as 90–100% within three to seven days after infection. Currently, WSSV is considered to be the deadliest viral pathogen in shrimp and many other crustaceans . A β-1,3f shrimp .FIV is a virus that can cause immunodeficiency syndrome in cats. FIV is spread mainly through bites between cats. The mortality rate of cats infected with FIV is not high. At present, vaccination can effectively prevent FIV infection .Inonotus obliquus had the best activity. The IC50 value is 0.80 ± 0.16 µg/mL. In addition, ethane extract of Inonotus obliquus, water and ethanol extract of Phellinus igniarius, ethanol extract of Cordyceps sinensis fruiting body, hexane extracts of Inonotus obliquus mycelium, ethanol extracts of Ganoderma lucidum, hexane extracts of Morchella esculenta fruiting bodies, and fresh fruiting bodies of Cordyceps sinensis also showed good activity [Ganoderma lucidum, Cordyceps sinensis, and Trametes versicolor. The experimental results in vitro show that HELP-TH1 can reduce the FIV load [In a study, seventeen kinds of medicinal fungi were extracted with water, ethanol, and hexane, respectively, and the inhibitory effect of the extract on FIV reverse transcriptase (FIV-rt) was studied. The results showed that the ethanol extract of activity . MoreoveFIV load .Fomes fomentarius and Ganoderma applanatum extract to the feed of the honeybee population, the titer of DWV and LSV virus in honeybees could be significantly reduced in a dose-dependent manner [DWV and LSV are two common viruses that can infect honeybees, which can cause honeybee wings to shrink and can also shorten their lifespan . Based ot manner .Ganoderma lucidum. The antiviral effect of rLZ-8 on infected NNV fish was verified by one experiment in vitro and three experiments in vivo. The results showed that rLZ-8 could activate the immune defense of fish and effectively fight against virus infection [Viral nerve necrosis disease is caused by NNV infection, which is a disease with high infectivity and high mortality. NNV mainly infects fish such as grouper, among which larvae and juveniles are the main targets of infection. This has caused great economic losses to the aquaculture industry . A protenfection .PCV-2 is a widespread epidemic virus in pigs. Pigs infected with PVC-2 usually show symptoms after weaning, resulting in severe damage to the immune system. All kinds of secondary diseases seriously threaten the life of pigs .Ganoderma lucidum polysaccharide liposome Lip-PS and inactivated PCV-2. Compared with inoculation inactivated PCV-2 only, combined vaccination can induce a more effective specific immune response to PCV-II infection [Liu et al., inoculated mice with nfection .PRRSV is an enveloped positive-strand RNA virus which is a pathogen causing porcine reproductive and respiratory syndrome (PRRS). Pigs will develop reproductive disorders and respiratory symptoms after infection. At present, there is no specific cure for PRRSV infection, but the virus spreads in many ways and it is difficult to prevent it .M-H-L-5 and 5α,8α-epidioxy-22E-ergosta-6,22-dien-3β-ol were isolated from the Cryptoporus volvatus. Through the antiviral experiment in vitro, the results showed that they had anti-PRRSV activity [Cryptoporus volvatus fruiting bodies in vivo and in vitro. The results showed that it had an effective antiviral effect on PRRSV infection. The extract mainly inhibited the entry of PRRSV and the synthesis of PRRSV RNA, and it could inhibit the replication of the virus in vivo. The survival rate of pigs was improved [Two monomer compounds, Cactivity ,95. In aimproved .PDCoV was first detected in fecal samples of Asian pigs in 2009. PDCoV is a porcine intestinal coronavirus. Clinical symptoms of PDCoV infection include diarrhea, dehydration, vomiting, and the death of newborn piglets. There is no effective drug to treat it at present .Cryptoporus volvatus. The in vitro results showed that EP could effectively prevent the attachment and entry of PDCoV. PDCoV may activate p38/MAPK signal pathway to promote its replication, activate the NF-κB signal pathway to stimulate the expression of many cytokines, and cause inflammation. EP treatment can inhibit p38 and NF-κB activation induced by PDCoV infection [An ergosterol peroxide EP was extracted from nfection . In vivonfection .Lentinus edodes. The results showed that the three extracts showed antiviral activity and mainly played an inhibitory role in the early stage of virus infection [BoHV-1, a DNA virus classified as an alpha herpes virus, is the main pathogen of cattle. Infectious bovine rhinotracheitis, abortion, infectious pustular vulvovaginitis, and other symptoms often occur in infected cattle . Anti-Bonfection .NDV is the main cause of Newcastle disease (ND). NDV is usually parasitic in chickens. It was first discovered as early as 1926, with high mortality and high infectivity. At this stage, vaccination is the best choice to prevent NDV infection .Ganoderma lucidum. The results showed that methanol and n-butanol fractions had stronger anti-neuraminidase activity, which may be related to the acidic pH value of Ganoderma lucidum extract and the effect of flavonoids on NDV neuraminidase activity [Ganoderma lucidum polysaccharide GLP can significantly promote the proliferation of lymphocytes and increase the level of interferon-γ (IFN-α) mRNA in vitro. In vivo experiments showed that oral GLP could significantly promote lymphocyte proliferation and improve serum antibody titer in chickens. This shows that GLP can be used as a good adjuvant in combination with vaccines [Auricularia auricula. After chlorosulfonic acid–pyridine method modification, their inhibitory effects on NDV were evaluated in vitro. Compared with the non-modified polysaccharides, the sulfated polysaccharides significantly enhanced their antiviral activity. This is related to the role of sulfated polysaccharides in the early, middle, and late stages of entering cells from the virus [Cordyceps militaris polysaccharides CMP40 and CMP50 could stimulate the proliferation of lymphocytes and increase the titer of serum antibody and the levels of interferon and IL-4. It is suggested that CMP40 and CMP50 can significantly improve the immune effect of Newcastle disease vaccine and are expected to be used as a new type of immune adjuvant [The anti-neuraminidase activity of NDV was tested with extracts from different organic soluble fractions of activity . Ganodervaccines . Moreovehe virus . In an iadjuvant .Hericium erinaceus polysaccharide (HEP) can effectively relieve the clinical symptoms and reduce the mortality of Muscovy ducks infected with MDRV. β-1,3 glucan (BG) in Schizophyllum commune can improve the immune level of shrimp to resist WSSV. Fomes fomentarius and Ganoderma applanatum extracts could significantly reduce the titer of DWV and LSV viruses in honeybees. The recombinant protein rLZ-8 in Ganoderma lucidum can activate the immune defense of fish and effectively combat virus infection. EP, a peroxidized ergosterol from the Cryptoporus volvatus, can reduce the pathological manifestations caused by PDCoV infection and reduce the viral load of piglets. Ganoderma lucidum polysaccharide GLP and Cordyceps militaris polysaccharide CMP40, CMP50 can significantly improve the immune effect of Newcastle disease vaccine. These substances are expected to be used as a food supplement or agents for veterinary practice.Medicinal fungi also have good prospects in the fight against animal viruses. A number of studies have shown that medicinal fungal extracts have good efficacy in animals. TMV is a common plant RNA virus, which mainly infects tobacco, tomato, and other crops. Plants infected with TMV will appear with symptoms such as yellowing and the wrinkling of leaves, which cause great inconvenience to agricultural production .Omphalia lapidescens. The results of in vitro experiments showed that all the five compounds had anti-tobacco mosaic virus activity [Fomes fomentarius. After using BAS-F on tobacco leaves infected with TMV, it was found that BAS-F could completely inhibit leaf infection, and have no toxic effect on host plants [Two new steroid compounds, leiwansterols A and B, and three known compounds were isolated from activity . Furthert plants . Wang’s t plants .GBNV can cause sprout blight on legumes, tomatoes, peppers, potatoes, cotton, and other crops, which seriously restricts the development of the planting industry .Coprinopsis cinerea, Ganoderma lucidum, and Lentinula edodes was tested against GBNV in vitro. The results showed that spraying the mixed culture filtrate could reduce the number of pathological changes and the titer of the virus. Finally, through GC-MS analysis, it was found that Squalene, a triterpenoid in Ganoderma lucidum, may have a potential antiviral effect [The culture filtrate prepared from the mycelia extracts of l effect .Fomes fomentarius, showed significant inhibitory effect on TMV and no toxic effect. The culture filtrate of mycelia extracts from Coprinopsis cinerea, Ganoderma lucidum and Lentinula edodes could significantly reduce the titer of GBNV in plants. All these can provide important reference significance for the use of medicinal fungi extract in agricultural production.Although there are few studies on medicinal fungal extracts against plant viruses, several medicinal fungal extracts have good therapeutic effects on diseased plants in the existing studies. BAS-F, a polysaccharide in Poria cocos and Polyporus umbellatus, have been widely used in clinical practice. Because of the special properties of medicinal fungi, it is better than that of traditional medicine, which is more beneficial to be used as a kind of health food. At present, the cultivation of medicinal fungi is more convenient than before, not only from the trees in the field, but also through the fermentation of mycelia. Although there are great differences in morphology between the fruiting body and the mycelium, there is little difference in the content of various components. In addition, the wide use of molecular docking technology and the development of the corresponding database bring great convenience to the screening of antiviral drugs. It can be vividly compared to adults who have changed from looking for a needle in a haystack to looking for a needle in a river. Because of the high risk of virus experiments, people can only carry out research in laboratories with biosafety levels II, III, or higher. This poses a great obstacle to the development of antiviral drugs. The use of pseudovirus solves this problem well, allowing people to avoid unnecessary risks that existed in previous experiments. On the other hand, while studying antiviral drugs, we should not be limited to the virus itself. Sometimes it is possible to grasp multiple links in which the virus replicates or invades the cell and catches a target to fight the virus. The Pfizer COVID-19-specific drug Paxlovid is aimed at the 3CL protein target of the virus. In addition to antiviral drugs, vaccines are undoubtedly another way to fight the virus. A variety of active components in medicinal fungi can not only directly fight the virus, but also activate the immune response of the human body. The use of extracts of medicinal fungi as vaccine adjuvants can significantly improve the efficacy of the vaccine to better combat viral infection. From the outbreak of highly pathogenic poultry in 1997 to Severe Acute Respiratory Syndrome (SARS) in 2003, the influenza pandemic in 2009, and today’s COVID-19, we are facing not only the spread of a virus. The co-infection caused by the combined effect of various viruses on the human body is also a problem that we should consider. The biological treasure of medicinal fungi remains to be excavated.It can be seen from our review that medicinal fungi are not only crude extracts, but also that some single components, such as proteins, polysaccharides and terpenoids, can effectively combat viral infection. Some of these medicinal fungi also have inhibitory effects on a variety of viruses . The com