The Unusual Architecture of RNA-Dependent RNA Polymerase (RdRp)'s Catalytic Chamber Provides a Potential Strategy for Combination Therapy against COVID-19.

ABSTRACT: The unusual and interesting architecture of the catalytic chamber of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) was recently explored using Cryogenic Electron Microscopy (Cryo-EM), which revealed the presence of two distinctive binding cavities within the catalytic chamber. In this report, first, we mapped out and fully characterized the variations between the two binding sites, BS1 and BS2, for significant differences in their amino acid architecture, size, volume, and hydrophobicity. This was followed by investigating the preferential binding of eight antiviral agents to each of the two binding sites, BS1 and BS2, to understand the fundamental factors that govern the preferential binding of each drug to each binding site. Results showed that, in general, hydrophobic drugs, such a

SUBMITTER: Metwally K 

PROVIDER: S-EPMC10057333 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature