Targeting SARS-CoV-2 Macrodomain-1 to Restore the Innate Immune Response Using In Silico Screening of Medicinal Compounds and Free Energy Calculation Approaches.

ABSTRACT: Among the different drug targets of SARS-CoV-2, a multi-domain protein known as NSP3 is a critical element of the translational and replication machinery. The macrodomain-I, in particular, has been reported to have an essential role in the viral attack on the innate immune response. In this study, we explore natural medicinal compounds and identify potential inhibitors to target the SARS-CoV-2-NSP3 macrodomain-I. Computational modeling and simulation tools were utilized to investigate the structural-dynamic properties using triplicates of 100 ns MD simulations. In addition, the MM/GBSA method was used to calculate the total binding free energy of each inhibitor bound to macrodomain-I. Two significant hits were identified: 3,5,7,4'-tetrahydroxyflavanone 3'-(4-hydroxybenzoic acid) and 2-hydr

SUBMITTER: Mohammad A 

PROVIDER: S-EPMC10538035 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature