Genetic conservation across SARS-CoV-2 non-structural proteins - Insights into possible targets for treatment of future viral outbreaks

Abstract

The majority of SARS-CoV-2 therapeutic development work has focussed on targeting the spike protein, viral polymerase and proteases. As the pandemic progressed, many studies reported that these proteins are prone to high levels of mutation and can become drug resistant. Thus, it is necessary to not only target other viral proteins such as the non-structural proteins (NSPs) but to also target the most conserved residues of these proteins. In order to understand the level of conservation among these viruses, in this review, we have focussed on the conservation across RNA viruses, conservation across the coronaviruses and then narrowed our focus to conservation of NSPs across coronaviruses. We have also discussed the various treatment options for SARS-CoV-2 infection. A synergistic melding of bioinformatics, computer-aided drug-design and in vitro/vivo studies can feed into better understanding of the virus and therefore help in the development of small molecule inhibitors against the viral proteins.

Keywords: Bioinformatics; Computer-aided drug design; Conservation; Group IV viruses; Non-structural proteins (NSPs); SARS-CoV-2; Sequence alignment; Small molecule inhibitors.