Cyanobacterial metabolites as promising drug leads against the Mpro and PLpro of SARS CoV 2: an in silico analysis
Abstract A novel severe acute respiratory syndrome coronavirus (SARS CoV 2) has emerged as the causative agent behind the coronavirus disease 2019 (COVID 19) pandemic. Treatment efforts have been severely impeded due to the lack of specific effective antiviral drugs for the treatment of COVID associated pathologies. In the present research endeavour the inhibitory prospects of cyanobacterial metabolites were assessed at the active binding pockets of the two vital SARS CoV 2 proteases namely, main protease (Mpro) and the papain like protease (PLpro) that proteolytically process viral polyproteins and facilitate viral replication, employing an in silico molecular interaction based approach. It was evident from our analysis based on the binding energy scores that the metabolites cylindrospermopsin, deoxycylindrospermopsin, carrageenan, cryptophycin 52, eucapsitrione, tjipanazole, tolyporphin and apratoxin A exhibited promising inhibitory potential against the SARS CoV 2 Mpro. The compounds cryptophycin 1, cryptophycin 52 and deoxycylindrospermopsin were observed to display encouraging binding energy scores with the PLpro of SARS CoV 2. Subsequent estimation of physicochemical properties and potential toxicity of the metabolites followed by robust molecular dynamics simulations and analysis of MM PBSA energy scoring function established deoxycylindrospermopsin as the most promising inhibitory candidate against both SARS CoV 2 proteases. Present research findings bestow ample scopes to further exploit the potential of deoxycylindrospermopsin as a successful inhibitor of SARS CoV 2 in vitro and in vivo and pave the foundation for the development of novel effective therapeutics against COVID 19. Communicated by Ramaswamy H. Sarma
Journal of biomolecular structure dynamics