| dc.description.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-asso-
ciated 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 pol-
yproteins 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 cylindrosper-
mopsin, deoxycylindrospermopsin, carrageenan, cryptophycin 52, eucapsitrione, tjipanazole, tolypor-
phin 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 physico-
chemical 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. | en_US |
