Discovery of Small Molecule Inhibitors of the SARS-CoV-2 endoribonuclease Nsp15

Abstract

A highly contagious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) emerged in China, spreading over all continents. Despite the notable efforts to control the rapid spread of SARS-CoV-2 through maintaining social distances and getting people vaccinated, the number of infected people continues to rise. Consequently, there is an urgent need for developing an antiviral drug against SARS-CoV-2. Nonstructural protein 15 (Nsp15) is a unique endoribonuclease enzyme belonging to the Nendo-U family. Targeting a highly conserved and essential protein like Nsp15 might contribute to developing an effective drug against all coronaviruses. The objective of this work is to suggest a set of commercial small molecules inhibitors against the target Nsp15 using an in silico approach of virtual screening and molecular docking. Our results revealed 25 molecules bind to the active site of Nsp15 and may potentially inhibit endoribonuclease activity responsible for the protein interference with the innate immune response.