In Silico Insights into the SARS CoV-2 Main Protease Suggest NADH Endogenous Defences in the Control of the Pandemic Coronavirus Infection

6533b834fe1ef96bd129e0e7

RESEARCH PRODUCT

In Silico Insights into the SARS CoV-2 Main Protease Suggest NADH Endogenous Defences in the Control of the Pandemic Coronavirus Infection

Carla Gentile Antonino Lauria Annamaria Martorana

subject

Models Molecular 0301 basic medicine Aging medicine.medical_treatment coronavirus lcsh:QR1-502 Viral Nonstructural Proteins medicine.disease_cause lcsh:Microbiology 0302 clinical medicine Settore BIO/10 - Biochimica Coronavirus 3C Proteases Coronavirus virus diseases Lopinavir Hypothesis Molecular Docking Simulation Cysteine Endopeptidases Drug repositioning Infectious Diseases 030220 oncology & carcinogenesis Coronavirus Infections Oxidation-Reduction medicine.drug DNA damage In silico Pneumonia Viral Biology Antiviral Agents HIV-protease Betacoronavirus 03 medical and health sciences SARS-CoV-2 main protease Virology medicine Humans Computer Simulation Protease Inhibitors Pandemics Binding Sites Protease SARS-CoV-2 Drug Repositioning COVID-19 HIV Protease Inhibitors DRUDIT web service molecular docking NAD biology.organism_classification Virology Settore CHIM/08 - Chimica Farmaceutica COVID-19 Drug Treatment coronaviru 030104 developmental biology NADH Ritonavir Betacoronavirus DNA Damage

description

COVID-19 is a pandemic health emergency faced by the entire world. The clinical treatment of the severe acute respiratory syndrome (SARS) CoV-2 is currently based on the experimental administration of HIV antiviral drugs, such as lopinavir, ritonavir, and remdesivir (a nucleotide analogue used for Ebola infection). This work proposes a repurposing process using a database containing approximately 8000 known drugs in synergy structure- and ligand-based studies by means of the molecular docking and descriptor-based protocol. The proposed in silico findings identified new potential SARS CoV-2 main protease (MPRO) inhibitors that fit in the catalytic binding site of SARS CoV-2 MPRO. Several selected structures are NAD-like derivatives, suggesting a relevant role of these molecules in the modulation of SARS CoV-2 infection in conditions of cell chronic oxidative stress. Increased catabolism of NAD(H) during protein ribosylation in the DNA damage repair process may explain the greater susceptibility of the elderly population to the acute respiratory symptoms of COVID-19. The molecular modelling studies proposed herein agree with this hypothesis.

year	journal	country	edition	language
2020-07-01

10.3390/v12080805 http://hdl.handle.net/10447/493108