Biochemical computational therapeutic approach towards the discovery of natural product noncovalent inhibitors of SARS-CoV-2 RNA-dependent RNA polymerase

Abstract

COVID-19 remains to be a disastrous pandemic chaotically affecting our lives to this day. This disease is caused by the new coronavirus, SARS-CoV-2. Like other coronaviruses and RNA viruses, SARS-CoV-2 replication and transcription largely relies on the activity of RNA-dependent RNA polymerase (RdRp). This enzyme produces a complementary RNA molecule from a template one. The necessity of this enzyme for the viral lifecycle has made it an attractive target for combating many RNA viruses. The famous RdRp inhibitor remdesivir has been granted use for hospitalized COVID-19 patients. In this work, we investigate a library of natural products with the aim of discovering new RdRp inhibitors for potential therapeutic purposes. The study comprises extensive biochemical docking and molecular filtration of the database where the resultant hits were evaluated for other molecular properties and pharmacophoric features. Two hit compounds were discovered to be potential therapeutic RdRp inhibitors, Sennoside B and Ginsenoside B2. The metabolites of these compounds were also predicted to investigate whether they would possess extended activity against the enzyme.