The Repurposed Drugs Suramin and Quinacrine Cooperatively Inhibit SARS-CoV-2 3CLpro In Vitro

Viruses. 2021 May 10;13(5):873. doi: 10.3390/v13050873.


Since the first report of a new pneumonia disease in December 2019 (Wuhan, China) the WHO reported more than 148 million confirmed cases and 3.1 million losses globally up to now. The causative agent of COVID-19 (SARS-CoV-2) has spread worldwide, resulting in a pandemic of unprecedented magnitude. To date, several clinically safe and efficient vaccines (e.g., Pfizer-BioNTech, Moderna, Johnson & Johnson, and AstraZeneca COVID-19 vaccines) as well as drugs for emergency use have been approved. However, increasing numbers of SARS-Cov-2 variants make it imminent to identify an alternative way to treat SARS-CoV-2 infections. A well-known strategy to identify molecules with inhibitory potential against SARS-CoV-2 proteins is repurposing clinically developed drugs, e.g., antiparasitic drugs. The results described in this study demonstrated the inhibitory potential of quinacrine and suramin against SARS-CoV-2 main protease (3CLpro). Quinacrine and suramin molecules presented a competitive and noncompetitive inhibition mode, respectively, with IC50 values in the low micromolar range. Surface plasmon resonance (SPR) experiments demonstrated that quinacrine and suramin alone possessed a moderate or weak affinity with SARS-CoV-2 3CLpro but suramin binding increased quinacrine interaction by around a factor of eight. Using docking and molecular dynamics simulations, we identified a possible binding mode and the amino acids involved in these interactions. Our results suggested that suramin, in combination with quinacrine, showed promising synergistic efficacy to inhibit SARS-CoV-2 3CLpro. We suppose that the identification of effective, synergistic drug combinations could lead to the design of better treatments for the COVID-19 disease and repurposable drug candidates offer fast therapeutic breakthroughs, mainly in a pandemic moment.

Keywords: 3CLpro; COVID-19; SARS-CoV-2; main protease; quinacrine; repurposing approved drugs; suramin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology
  • COVID-19 / drug therapy
  • COVID-19 Vaccines / pharmacology
  • Coronavirus 3C Proteases / antagonists & inhibitors
  • Coronavirus 3C Proteases / drug effects*
  • Coronavirus 3C Proteases / metabolism
  • Cysteine Endopeptidases / metabolism
  • Drug Repositioning
  • Humans
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Pandemics
  • Protease Inhibitors / pharmacology
  • Quinacrine / metabolism
  • Quinacrine / pharmacology*
  • SARS-CoV-2 / drug effects
  • SARS-CoV-2 / metabolism
  • SARS-CoV-2 / pathogenicity
  • Suramin / metabolism
  • Suramin / pharmacology*
  • Viral Nonstructural Proteins


  • Antiviral Agents
  • COVID-19 Vaccines
  • Protease Inhibitors
  • Viral Nonstructural Proteins
  • Suramin
  • Cysteine Endopeptidases
  • Coronavirus 3C Proteases
  • Quinacrine