Virtual Screening of Natural Compounds Targeting Proteases of Coronaviruses and Picornaviruses

Abstract

Viral protease plays an essential role in viral replication and maturation. Therefore, the enzyme active site is an attractive target for the antiviral agents. The “picornavirus-like supercluster” proteases are chymotrypsin-like cysteine proteases associated with viruses in the families Picornaviridae and Coronaviridae. They contain catalytic residues for proteolysis activity in their active sites, to cleave viral proteins during their replication. In this chapter, we describe the procedure of virtual screening for specific molecules targeting feline infectious peritonitis virus (FIPV), a variant of feline coronavirus (FCoV), protease (FIPV 3CLpro), and foot-and-mouth disease virus (FMDV 3Cpro). The study of FIPV 3CLpro can be a model for other emerging coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2 while the methods related to FMDV 3Cpro can also be a useful guide for other picornaviruses. The small and active natural molecules were retrieved from available compound libraries. Several software and web servers are freely accessible for academics to perform in silico assay that narrow down the compound-searching scope for further validation in antiviral drug development.