E2^UbcH5B-derived peptide ligands target HECT E3-E2 binding site and block the Ub-dependent SARS-CoV-2 egression: A computational study.

ABSTRACT: Homologous to E6AP carboxyl-terminus (HECT)-type E3 ligase performs ubiquitin (Ub)-proteasomal protein degradation via forming a complex with E2∼Ub. Enveloped viruses including SARS-CoV-2 escape from the infected cells by harnessing the E-class vacuolar protein-sorting (ESCRT) machinery and mimic the cellular system through PPAY motif-based linking to HECT Ub ligase activity. In the present study, we have characterized the binding pattern of E2^UbcH5B to HECT domains of NEDD4L, WWP1, WWP2, HECW1, and HECW2 through in silico analysis to isolate the E2^UbcH5B-specific peptide inhibitors that may target SARS-CoV-2 viral egression. Molecular dynamics analysis revealed more opening of E2^UbcH5B-binding pocket upon binding to HECT^NEDD4L, HECT^WWP1

SUBMITTER: Zahid S 

PROVIDER: S-EPMC9124161 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature