Discovery of small molecule entry inhibitors targeting the linoleic acid binding pocket of SARS-CoV-2 spike protein.

Spike glycoprotein has a significant role in the entry of SARS-CoV-2 to host cells, which makes it a potential drug target. Continued accumulation of non-synonymous mutations in the receptor binding domain of spike protein poses great challenges in identifying antiviral drugs targeting this protein. This study aims to identify potential entry inhibitors of SARS-CoV-2 using virtual screening and molecular dynamics (MD) simulations from three distinct chemical libraries including Pandemic Response Box, Drugbank and DrugCentral, comprising 6971 small molecules.

study identifies peptide inhibitors that negate the effect of non-synonymous mutations in major drug targets of SARS-CoV-2 variants.

Since its advent in December 2019, SARS-CoV-2 has diverged into multiple variants with differing levels of virulence owing to the accumulation of mutations in its genome. The structural changes induced by non-synonymous mutations in major drug targets of the virus are known to alter the binding of potential antagonistic inhibitors. Here, we analyzed the effects of non-synonymous mutations in major targets of SARS-CoV-2 in response to potential peptide inhibitors.