FIELD

The present application generally relates to antiviral compositions and methods. More particularly, the present application relates to antiviral compositions comprising a plant MOMO30 protein for treatment and prevention of viral inventions.

BACKGROUND

The conventional approach to HIV treatment, highly active anti-retroviral therapy (HAART) involves the use of combinations of anti-retrovirals such as bictegravir/tenofovir alafenamide/emtricitabine (Biktarvy), dolutegravir (Tivicay) plus tenofovir/emtricitabine (Truvada), raltegravir (Isentress) plus tenofovir/emtricitabine (Truvada), and abacavir/dolutegravir/lamivudine (Triumeq). HAART enables the reduction of blood plasma viral load to undetectable levels for extended periods of time. On average, 50% of patients see their plasma viral loads fall to less than 50 copies/ml after a treatment of around 12 months. However, antiviral treatments, including HAART are not without flaws and do not carry the assurance of a long-term cure.

Suppression of viral loads and slowing of the reduction in in CD4 counts allows for prolonged periods of relatively normal life. However, even newer formulations of HAART have associated toxicity and risk of developing antiretroviral resistance. Most importantly, treatment must be maintained for the life of the patient in ordered to maintain the benefits. In the vast majority of cases, withdrawal of HAART results in rebound of viral loads and disease progression. HAART is expensive to maintain and is beyond the means of many individuals in third-world countries. This is particularly true in African populations, which have the highest incidence of HIV/AIDS.

In view of the foregoing, there is a need for improved and less costly therapeutic options for treating HIV and other viral infections. In particular, there is a need for a treatment that can be administered short-term and induce a long suppression of viral loads.

SUMMARY

In one aspect, the present application relates to a composition comprising or expressing a MOMO30 protein. The MOMO30 protein has a size of about 30 kDa, is capable of binding HIV gp120, is stable to both heat and protease treatment, is non-toxic to cells at therapeutic levels, and can block the interaction of viral glycoproteins to cellular receptors resulting in inactivation of an enveloped virus, such as HIV-1.

In another aspect, the present application relates to a method for preventing or reducing symptoms of HIV infection, comprising orally administering to a subject in need thereof an effective amount of a MOMO30 protein composition prepared by a method includes the steps of: (a) drying plant comprising MOMO30 protein; (b) extracting the dried plant in aqueous media; (c) lysing cells from the extracted plant to form a plant cell lysate; (d) centrifuging the plant cell lysate to remove debris and particulates to form a clarified plant cell lysate; and (e) forming the MOMO30 protein composition by: (i) passing the clarified plant cell lysate through a molecular weight cut-off filter and collecting the MOMO30-containing retentate; or (ii) purifying the MOMO30 protein from the clarified plant cell lysate by immunoaffinity purification using an anti-MOMO30 antibody. The MOMO30 protein composition formed therefrom is orally administered to the subject in liquid or dried form such that the MOMO30 protein composition is substantially free of plant components less than 10 kDa in size and includes a protein of about 30 kDa in size that is stable after boiling at 100° C. for 20 min, that binds HIV gp120, and comprises the amino acid sequence of SEQ ID NO: 1.

In certain preferred embodiments, the plant comprising MOMO30 protein is a member of theMomordicagenus. In a more particular embodiment, the plant isMomordica balsamina.

In some embodiments, the method for preparing the MOMO30 protein composition comprises the step of subjecting the plant extract to immunoaffinity purification prior to administration. In other embodiments, the method includes the step of eluting the MOMO30 retentate in an aqueous buffer to form an aqueous MOMO30 protein composition in solution.

In some embodiments, the MOMO30 protein composition is dried and administered to the subject in a dried form. In some embodiments, the MOMO30 protein composition is dried and orally administered to the subject in a dried form, such as a capsule or tablet. In other embodiments, the MOMO30 protein composition is administered to the subject in liquid form. In certain particular embodiments the MOMO30 protein composition is formulated as an herbal tea for oral administration in liquid form.

In another aspect, a method for preparing a MOMO30 protein composition, includes the steps of: (a) drying a plant comprising MOMO30 protein; (b) extracting the dried plant in aqueous media; (c) lysing cells from the extracted plant to form a plant cell lysate; (d) centrifuging the plant cell lysate to remove debris and particulates to form a clarified plant cell lysate; and (e1) passing the plant cell lysate through a molecular weight cut-off filter and collecting the MOMO30-containing retentate, or (e2) purifying the MOMO30 protein from the clarified plant cell lysate by immunoaffinity purification using an anti-MOMO30 antibody, such that the MOMO30 protein composition formed therefrom is substantially free of plant components less than 10 kDa in size and includes a protein of about 30 kDa in size that is stable after boiling at 100° C. for 20 min, that binds HIV gp120, and that comprises the amino acid sequence of SEQ ID NO: 1.

In certain preferred embodiments, the plant comprising MOMO30 protein is a member of theMomordicagenus. In a more particular embodiment, the plant isMomordica balsamina.

In another aspect, the present application provides a pharmaceutical composition containing MOMO30 protein for preventing or reducing symptoms of HIV infection in which the pharmaceutical composition is prepared by a method including the steps of: (a) drying a plant comprising MOMO30 protein; (b) extracting the dried plant in aqueous media; (c) lysing cells from the extracted plant to form a plant cell lysate; (d) centrifuging the plant cell lysate to remove debris and particulates to form a clarified plant cell lysate; (e) preparing a dried MOMO30 protein composition therefrom; (f) adding one or more pharmaceutically acceptable carriers to the dried MOMO30 protein composition, and (g) forming a pharmaceutically acceptable oral composition therefrom in the form of a powder, capsule, tablet, or liquid. The composition resulting therefrom is substantially free of plant components less than 10 kDa in size, and includes a protein of about 30 kDa in size that is stable after boiling at 100° C. for 20 min, that binds HIV gp120, and that comprises the amino acid sequence of SEQ ID NO: 1.

In certain preferred embodiments, the plant comprising MOMO30 protein is a member of theMomordicagenus. In a more particular embodiment, the plant isMomordica balsamina.

In some embodiments, the clarified plant cell lysate is passed through a 30-50 kDa molecular weight cut-off filter prior to preparing the dried MOMO30 protein composition. In other embodiments, the clarified plant cell lysate is subjected to immunoaffinity purification using an anti-MOMO30 antibody prior to preparing the dried MOMO30 protein composition for oral administration.

In some embodiments, the pharmaceutical composition is administered in the form of a powder. In other embodiments, the pharmaceutical composition is administered in the form of a capsule or tablet. In yet other embodiments, the pharmaceutical composition is administered in the form of a liquid.

In another aspect, the present application comprises a MOMO30 protein. In another embodiment, the composition comprises a nucleic acid encoding or operatively linked to express a MOMO30 protein. In preferred embodiments, the MOMO30 protein is derived from a plant species of theMomordicagenus.

A particularly preferred species isMomordica balsamina.

In another aspect, a method for preventing or treating a viral infection comprises administering to a subject in need thereof, a MOMO30 protein or MOMO30-encoded nucleic acid by in vivo or ex vivo gene therapy.

