Modeling the Structure-Activity Relationship of Arbidol Derivatives and Other SARS-CoV-2 Fusion Inhibitors Targeting the S2 Segment of the Spike Protein.

ABSTRACT: Umifenovir (Arbidol) has been reported to exhibit some degree of efficacy in multiple clinical trials for the treatment of COVID-19 as a monotherapy. It has also demonstrated synergistic inhibition of SARS-CoV-2 with other direct-acting antivirals such as Remdesivir. A computational approach was used to identify the most favorable binding site to the SARS-CoV-2 Spike S2 segment and to perform virtual screening. Compounds selected from modeling were evaluated in a live SARS-CoV-2 infection assay. An Arbidol (ARB) derivative with substitutions at both the C-4 and C-6 positions was found to exhibit a modest improvement in activity and solubility properties in comparison to ARB. However, all of the derivatives were found to only be partial inhibitors, rather than full inhibitors in a virus-ind

SUBMITTER: Freidel MR 

PROVIDER: S-EPMC8691200 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature