Investigation of small molecule inhibitors of the SARS-CoV-2 papain-like protease by all-atom microsecond modelling, PELE Monte Carlo simulations, and in vitro activity inhibition.
Chem Phys Lett
; : 139294, 2021 Dec 18.
Article
in English
| MEDLINE | ID: covidwho-1588009
ABSTRACT
The SARS-CoV-2 papain-like (PLpro) protease is essential for viral replication. We investigated potential antiviral effects of hypericin relative to the well-known noncovalent PLpro inhibitor GRL-0617. Molecular dynamics and PELE Monte Carlo simulations highlight favourable binding of hypericin and GRL-0617 to the naphthalene binding pocket of PLpro. Although not potent as GRL-0617 (45.8 vs 1.6µM for protease activity, respectively), in vitro fluorogenic enzymatic assays with hypericin show concentration-dependent inhibition of both PLpro protease and deubiquitinating activities. Given its use in supplementations and the FDA conditional approval of a synthetic version, further evaluation of hypericin as a potential SARS-CoV-2 antiviral is warranted.
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International databases
Database:
MEDLINE
Type of study:
Experimental Studies
Language:
English
Journal:
Chem Phys Lett
Year:
2021
Document Type:
Article
Affiliation country:
J.cplett.2021.139294
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