Combining Computational and Experimental Evidence on the Activity of Antimalarial Drugs on Papain-Like Protease of SARS-CoV-2: A Repurposing Study.
Chem Biol Drug Des
; 2022 Nov 30.
Article
in English
| MEDLINE | ID: covidwho-2278247
ABSTRACT
The development of inhibitors that target the papain-like protease (PLpro) has the potential to counteract the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent causing coronavirus disease 2019 (COVID-19). Based on a consideration of its several downstream effects, interfering with PLpro would both revert immune suppression exerted by the virus and inhibit viral replication. By following a repurposing strategy, the current study evaluates the potential of antimalarial drugs as PLpro inhibitors, and thereby the possibility of their use for treatment of SARS-CoV-2 infection. Computational tools were employed for structural analysis, molecular docking and molecular dynamics simulations to screen antimalarial drugs against PLpro, and in silico data were validated by in vitro experiments. Virtual screening highlighted amodiaquine and methylene blue as the best candidates, and these findings were complemented by the in vitro results that indicated amodiaquine as a µM PLpro deubiquitinase inhibitor. The results of this study demonstrate that the computational workflow adopted here can correctly identify active compounds. Thus, the highlighted antimalarial drugs represent a starting point for the development of new PLpro inhibitors through structural optimization.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Type of study:
Experimental Studies
/
Prognostic study
Language:
English
Journal subject:
Biochemistry
/
Pharmacy
/
Pharmacology
Year:
2022
Document Type:
Article
Affiliation country:
Cbdd.14187
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