In-silico screening to delineate novel antagonists to SARS-CoV-2 nucleocapsid protein

Abstract

Since its inception, SARS-CoV-2 has crossed all borders and continues rampaging around the globe, causing profound economic damage and heavy burden on the scientific community and the healthcare fraternity and facilities. With the emergence of new variants, the global pandemic has prolonged and raised concerns regarding the existing therapies. Most of the identified mutants have the potential to exacerbate the already existing crisis. In line with the urgent need for promising antivirals against the novel coronavirus, we conducted an in-silico drug docking study using SeeSAR and other bioinformatics tools and identified prospective molecules that target the nucleocapsid protein of SARS-CoV-2. The highly conserved N protein plays a crucial role in viral assembly and pathogenicity by interacting with the host ribosomal subunits and suppressing nonsense mediated decay (NMD) of viral mRNA by the host cell. In the current study, FDA approved drugs were docked into pockets created within the N protein including the crucial conserved residues and analyzed for their affinity. The docked compounds give us novel plausible models that can be inspected further and paves way for the development of potent therapeutics against SARS-CoV-2.