VIRTUAL SCREENING OF CYANOBACTERIAL METABOLITES AS INHIBITORS OF SARS-CoV-2 HOST CELL ENTRY, VIRAL REPLICATION, AND HOST IMMUNITY MODULATION INFECTIVE MECHANISMS

Abstract

The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) emerged in December 2019 leading to a global pandemic and lockdowns in different countries including the Philippines. There is an oral antiviral treatment, Paxlovid, produced by Pfizer that is currently authorized for emergency use to treat COVID-19. However, there is still a necessity to discover specific antiviral drugs due to increasing cases worldwide. In this study, 56 cyanobacterial secondary metabolites were virtually screened for in silico inhibitory prospects against five main targeted proteins of SARS-CoV-2 involved in viral attachment, viral replication, and host immunity modulation mechanisms. Pharmacokinetic properties and toxicity predictions were also performed. Of the fifty-six secondary metabolites molecularly docked, compounds 1–7 showed favorable binding energy ranging from -10.9 to -8.0 kcal/mol against the spike’s ACE2 (angiotensin-converting enzyme 2) and GRP 78 (glucose-related protein 78) receptor binding domains, 3CLPRO (3-chymotrypsin-like protease), PLPRO (papain-like protease), and RdRp (RNA-dependent RNA-polymerase). Three compounds, scytonemin (1) a bisindole alkaloid dimer, cryptophycin (5) a macrolactam, and tjipanazole A2 (6) an indole alkaloid glucoside exhibited highest the binding affinities with BE’s ranging from -10.4 to -8.6 kcal/mol. Top-ranked ligands 1–7 also demonstrated favorable pharmacokinetics with low toxicity risks.