SARS-CoV-2 RNA-dependent RNA polymerase complex as the potential antiviral target

Abstract

As the SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infection postures a danger to global health, developing specific anti-coronavirus therapeutics and prophylactics is necessary. To develop these novel therapeutics, identification and characterization of potential antiviral drug targets are required. One of the potential antiviral drug targets is the RNA- dependent RNA polymerase (RdRp) complex, which is involved in viral replication and is essential for virus survival. The structure of the RdRp complex includes the main catalytic subunit nsp12 along with two co-factors, nsp8 and nsp7, which stimulate the activity of nsp12. Inhibition of this polymerase complex will ultimately result in the inactivation of the virus. The main objective of this work includes purifying the catalytic subunit nsp12 and its co-factors nsp7 and nsp8. As the structure of this complex is available in the protein data bank (PDB), virtual screening of the compounds for an inhibitory activity has been done against this complex by using PyRx. Already published drugs like remdesivir, favipiravir, ribavirin, galidesivir are used as the positive controls to shortlist the top hits among the screened compounds based on binding an affinity. This study forms the basis for future biophysical and biochemical studies that can further lead us to find potential polymerase inhibitor molecules that may be a significant step towards the therapeutic development for deadly emerging infectious SARS-CoV-2.