Structural perspective of remdesivir bound to RNA polymerase of SARS-CoV-2 as a potential drug of COVID-19 : review

Abstract

Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infection. This pandemic was defining global health crisis with more than 896,000 deaths worldwide. SARS-CoV2 is positive strand RNA virus. The RNA-dependent RNA Polymerase (RdRp) enzyme plays main role in SARS-CoV2 genome replication and its transcription gene. The RdRp is composed of subunit named as viral non-structural proteins 12 (nsp12) with two accessory subunits, named nsp8 and nsp7. There are many potential drug and therapeutic option have been tried for COVID-19 but none have yet been approved as efficacy drug for COVID-19. One of the most potential inhibitors for treatment of COVID-19 through nsp12 mechanism is remdesivir. Remdesivir as potential drug reported inhibits the replication of SARS-CoV2 with direct interaction to RdRp. Here we provide an explanation from a structural perspective based on previous research publication data taken from PUBMED and Protein Data Bank (PDB ID 6YYT for SARS-CoV-2 replicating polymerase, PDB ID 7BV1 for the apo RdRp complex, and PDB ID 7BV2 for the template RNA and remdesivir–bound RdRp complex). Remdesivir complexed with RdRp complex showed that half of RNA template interact in the core of the RdRp. In addition, remdesivir terminates elongation with interact with covalent bound to the primer strand with key residues K545, S682, R555, T687, D623, S759, N691, D760, and D761. This understanding will lead to deeper understanding of remdesivir works mechanism as a suppressor for SARS-CoV2 replication through RNA-polymerase inhibition. Structural determination helps us to understand how this potential drug works in the inhibition of elongation of RNA in the atomic level. Although remdesivir is still considered inefficient to be main antiviral for COVID-19, structural information of the complex will be able to become a basic consideration in developing future antiviral drugs.