Interaction of hydroxychloroquine with SARS-CoV2 functional proteins using all-atoms non-equilibrium alchemical simulations.
Chem Commun (Camb)
; 56(62): 8854-8856, 2020 Aug 04.
Article
in English
| MEDLINE | ID: covidwho-635466
ABSTRACT
Using a combination of enhanced sampling molecular dynamics techniques and non-equilibrium alchemical transformations with full atomistic details, we have shown that hydroxychloroquine (HCQ) may act as a mild inhibitor of important functional proteins for SARS-CoV2 replication, with potency increasing in the series PLpro, 3CLpro, RdRp. By analyzing the bound state configurations, we were able to improve the potency for the 3CLpro target, designing a novel HCQ-inspired compound, named PMP329, with predicted nanomolar activity. If confirmed in vitro, our results provide a molecular rationale for the use of HCQ or of strictly related derivatives in the treatment of Covid-19.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
RNA-Dependent RNA Polymerase
/
Cysteine Endopeptidases
/
Papain
/
Viral Nonstructural Proteins
/
Molecular Dynamics Simulation
/
Hydroxychloroquine
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
Chem Commun (Camb)
Journal subject:
Chemistry
Year:
2020
Document Type:
Article
Affiliation country:
D0cc03558k
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