Prediction of binding of FDA approved drug Ledipasvir to SARS-CoV2 mutants: an in silico study

Abstract

The surge of variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is a global concern to public health as the mutations in the genome may alter the virulence of the virus, which poses a challenge to manage the disease. The virus depends on RNA dependent RNA polymerases [RdRp(s)] and its associated non-structural proteins for replication. Therefore, RdRp is a target of antiviral drugs. Several mutations in RdRp in SARS-CoV2 from all over the world have been identified. Some of the mutations are known to alter the RdRp structure. This may have an implication on the effectiveness of the drugs being approved for combating the disease. Therefore, we believe elaborate studies are necessary to identify and characterize mutations in RdRp with respect to drug binding ability. Herein, using molecular docking, we have studied the interaction of the approved drug, Ledipasvir, with wild type and different mutant RdRps to gain mechanistic insights into structural changes which can affect the drug binding and may be responsible for drug resistance. We observed a change in the binding energy of ledipasvir with wild type and mutant polymerases. Further, deviation in the orientation of the drug was observed in the case of mutants in comparison to wild type RdRp. These findings suggest that it is of utmost importance to study RdRp mutants to assess drug resistance.