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

Viruses. 2020 Jul 26;12(8):805. doi: 10.3390/v12080805.

Abstract

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.

Keywords: COVID-19; DRUDIT web service; HIV-protease; NADH; SARS-CoV-2 main protease; coronavirus; molecular docking.

MeSH terms

  • Aging / metabolism
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology*
  • Betacoronavirus / drug effects*
  • Betacoronavirus / enzymology*
  • Binding Sites
  • COVID-19
  • COVID-19 Drug Treatment
  • Computer Simulation
  • Coronavirus 3C Proteases
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / metabolism
  • Coronavirus Infections / virology
  • Cysteine Endopeptidases / chemistry*
  • DNA Damage
  • Drug Repositioning
  • HIV Protease Inhibitors / chemistry
  • HIV Protease Inhibitors / pharmacology
  • Humans
  • Models, Molecular
  • Molecular Docking Simulation
  • NAD / metabolism*
  • Oxidation-Reduction
  • Pandemics*
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / metabolism
  • Pneumonia, Viral / virology
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • SARS-CoV-2
  • Viral Nonstructural Proteins / antagonists & inhibitors*
  • Viral Nonstructural Proteins / chemistry*

Substances

  • Antiviral Agents
  • HIV Protease Inhibitors
  • Protease Inhibitors
  • Viral Nonstructural Proteins
  • NAD
  • Cysteine Endopeptidases
  • Coronavirus 3C Proteases