Anti-HCV, nucleotide inhibitors, repurposing against COVID-19

Life Sci. 2020 May 1;248:117477. doi: 10.1016/j.lfs.2020.117477. Epub 2020 Feb 28.

Abstract

Aims: A newly emerged Human Coronavirus (HCoV) is reported two months ago in Wuhan, China (COVID-19). Until today >2700 deaths from the 80,000 confirmed cases reported mainly in China and 40 other countries. Human to human transmission is confirmed for COVID-19 by China a month ago. Based on the World Health Organization (WHO) reports, SARS HCoV is responsible for >8000 cases with confirmed 774 deaths. Additionally, MERS HCoV is responsible for 858 deaths out of about 2500 reported cases. The current study aims to test anti-HCV drugs against COVID-19 RNA dependent RNA polymerase (RdRp).

Materials and methods: In this study, sequence analysis, modeling, and docking are used to build a model for Wuhan COVID-19 RdRp. Additionally, the newly emerged Wuhan HCoV RdRp model is targeted by anti-polymerase drugs, including the approved drugs Sofosbuvir and Ribavirin.

Key findings: The results suggest the effectiveness of Sofosbuvir, IDX-184, Ribavirin, and Remidisvir as potent drugs against the newly emerged HCoV disease.

Significance: The present study presents a perfect model for COVID-19 RdRp enabling its testing in silico against anti-polymerase drugs. Besides, the study presents some drugs that previously proved its efficiency against the newly emerged viral infection.

Keywords: COVID-19; Docking; Nucleotide inhibitors; RdRp; Sofosbuvir; Structural bioinformatics; Wuhan coronavirus.

MeSH terms

  • Adenosine Monophosphate / analogs & derivatives*
  • Adenosine Monophosphate / chemistry
  • Adenosine Monophosphate / metabolism
  • Alanine / analogs & derivatives*
  • Alanine / chemistry
  • Alanine / metabolism
  • Alphacoronavirus / enzymology
  • Alphacoronavirus / genetics
  • Amino Acid Sequence
  • Antiviral Agents / chemistry*
  • Antiviral Agents / metabolism
  • Betacoronavirus / enzymology*
  • Betacoronavirus / genetics
  • COVID-19
  • Catalytic Domain
  • Computational Biology / methods
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / virology
  • Drug Repositioning / methods
  • Guanosine Monophosphate / analogs & derivatives*
  • Guanosine Monophosphate / chemistry
  • Guanosine Monophosphate / metabolism
  • Guanosine Triphosphate / chemistry
  • Guanosine Triphosphate / metabolism
  • Humans
  • Molecular Docking Simulation
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / virology
  • Protein Binding
  • Protein Conformation, alpha-Helical
  • Protein Conformation, beta-Strand
  • Protein Interaction Domains and Motifs
  • RNA-Dependent RNA Polymerase / antagonists & inhibitors*
  • RNA-Dependent RNA Polymerase / chemistry
  • RNA-Dependent RNA Polymerase / metabolism
  • Ribavirin / chemistry*
  • Ribavirin / metabolism
  • SARS-CoV-2
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Sofosbuvir / chemistry*
  • Sofosbuvir / metabolism
  • Thermodynamics
  • Uridine Triphosphate / chemistry
  • Uridine Triphosphate / metabolism
  • Viral Proteins / antagonists & inhibitors*
  • Viral Proteins / chemistry
  • Viral Proteins / metabolism

Substances

  • Antiviral Agents
  • IDX184
  • Viral Proteins
  • remdesivir
  • Adenosine Monophosphate
  • Ribavirin
  • Guanosine Monophosphate
  • Guanosine Triphosphate
  • RNA-Dependent RNA Polymerase
  • Alanine
  • Uridine Triphosphate
  • Sofosbuvir

Supplementary concepts

  • COVID-19 drug treatment