Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study

Life Sci. 2020 Jul 15;253:117592. doi: 10.1016/j.lfs.2020.117592. Epub 2020 Mar 25.

Abstract

Aims: A new human coronavirus (HCoV), which has been designated SARS-CoV-2, began spreading in December 2019 in Wuhan City, China causing pneumonia called COVID-19. The spread of SARS-CoV-2 has been faster than any other coronaviruses that have succeeded in crossing the animal-human barrier. There is concern that this new virus will spread around the world as did the previous two HCoVs-Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS)-each of which caused approximately 800 deaths in the years 2002 and 2012, respectively. Thus far, 11,268 deaths have been reported from the 258,842 confirmed infections in 168 countries.

Main methods: In this study, the RNA-dependent RNA polymerase (RdRp) of the newly emerged coronavirus is modeled, validated, and then targeted using different anti-polymerase drugs currently on the market that have been approved for use against various viruses.

Key findings: The results suggest the effectiveness of Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir as potent drugs against SARS-CoV-2 since they tightly bind to its RdRp. In addition, the results suggest guanosine derivative (IDX-184), Setrobuvir, and YAK as top seeds for antiviral treatments with high potential to fight the SARS-CoV-2 strain specifically.

Significance: The availability of FDA-approved anti-RdRp drugs can help treat patients and reduce the danger of the mysterious new viral infection COVID-19. The drugs mentioned above can tightly bind to the RdRp of the SARS-CoV-2 strain and thus may be used to treat the disease. No toxicity measurements are required for these drugs since they were previously tested prior to their approval by the FDA.

Keywords: COVID-19; Drug repurposing; Molecular docking; RdRp; SARS-CoV-2; Structural bioinformatics.

MeSH terms

  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Betacoronavirus / drug effects*
  • COVID-19 / drug therapy
  • Coronavirus Infections / drug therapy
  • Humans
  • Molecular Docking Simulation*
  • Nucleic Acid Synthesis Inhibitors / chemistry*
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • Nucleosides / analogs & derivatives
  • RNA-Dependent RNA Polymerase / antagonists & inhibitors*
  • SARS-CoV-2

Substances

  • Antiviral Agents
  • Nucleic Acid Synthesis Inhibitors
  • Nucleosides
  • RNA-Dependent RNA Polymerase

Supplementary concepts

  • COVID-19 drug treatment