In silico molecular docking of SARS-CoV-2 surface proteins with microbial non-ribosomal peptides: identification of potential drugs.

Abstract

Outbreak of COVID-19 by SARS-CoV-2 infection caused severe acute respiratory syndrome that has been declared a public health emergency of international concern. To control infections, there is urgent need to develop an effective therapeutic strategy. COVID-19 viral spike glycoprotein and proteases play major role in viral entry and mediating virus replication and spread and thus can serve as potential antiviral drug target. Being highly specific, efficacious and safe, peptides hold their place in therapeutics. In present study, molecular docking of 21 pharmacologically active non ribosomal peptides (NRPs) from marine microbes with SARS-CoV-2 spike glycoprotein and papain such as protease was done. Dactinomycin, Tyrocidine A and Gramicidin S showed highest binding interaction with target proteins. The binding affinity of Dactinomycin and Gramicidin S docked with SARS-CoV-2 spike glycoprotein was - 12.4 kcal/mol and - 11.4 kcal/mol, respectively. This suggested their potential to destabilize SARS spike protein binding with human host ACE2 receptor and thus hindering viral entry to the cells. Binding affinity of Tyrocidine A and Gramicidin S with SARS-CoV-2 papain-like protease was - 13.1 kcal/mol and - 11.4 kcal/mol, respectively which might be inhibited COVID-19 by acting on the protease. Gramicidin S showed same binding affinity for both target proteins and thus expected to be most potent. Based on the binding energy score, it was suggested that these pharmacologically active NRPs are potential molecules to be tested against SARS-CoV-2 and used to develop effective antiviral drugs.