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. This journal is

Interaction of hydroxychloroquine with SARS-CoV2 functional proteins using all-atoms non-equilibrium alchemical simulations

Guarnieri G.;Iannone F.
2020

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. This journal is
COVID-19
SARS-CoV-2
Betacoronavirus
Binding Sites
Catalytic Domain
Coronavirus 3C Proteases
Coronavirus Infections
Coronavirus Papain-Like Proteases
Cysteine Endopeptidases
Humans
Hydroxychloroquine
Pandemics
Papain
Pneumonia, Viral
RNA-Dependent RNA Polymerase
Viral Nonstructural Proteins
Molecular Dynamics Simulation
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12079/57272
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