Remdesivir and Chloroquine as Potential Broad-Spectrum Antiviral Drugs

Remdesivir As A Potential Broad-Spectrum Antiviral Drug

(From Potential Antiviral Agents for Coronavirus-es: Compounds, Herbal Products, and Drug Targets)

  • The nucleoside analogue GS-5734 (remdesivir) has been found to inhibit human and zoonotic CoVs (Agostini et al., 2018).
  • GS-5734 may inhibit murine hepatitis virus (MHV), SARS-CoV and MERS-CoV.
  • GS-5734 could be a broad-spectrum drug to protect against current and novel CoVs.
  • The effects of nucleoside-based therapeutics may be blocked by a proofreading exoribonuclease (ExoN), e.g., the CoV nsp14 ExoN.
  • To solve the problem, a group β-2a CoV was added to the nucleotide prodrug remdesivir (GS-5734).
  • Higher and nontoxic concentrations of GS-5734 may help overcome the viral resistance.
  • Further development of GS-5734 has the potential to make it as an effective pan-CoV antiviral agent (Agostini et al., 2018).        

The Broad-Spectrum Antiviral Effects of Chloroquine

(From Potential Antiviral Agents for Coronavirus-es: Compounds, Herbal Products, and Drug Targets)

  • HCoVs including HCoV-OC43 may cause 15 to 30% of mild upper respiratory tract infections (Keyaerts et al., 2009).
  • Chloroquine has been used for its antimalarial functions, and may inhibit HCoV-OC43 replication.
  • Chloroquine may also prevent HCoV-OC43-induced death in newborn mice given through maternal milk.
  • The high survival rate occurred when the mother mice were given the drug with 15 mg/kg of body weight/day.
  • Survival rates declined in a dose-dependent manner, with 88% survival when treated with 5 mg/kg and 13% survival with 1 mg/kg.
  • Chloroquine has been found effective against HCoV-OC43 infection in mice as a potential drug (Keyaerts et al., 2009).

References:

Agostini, M. L., Andres, E. L., Sims, A. C., Graham, R. L., Sheahan, T. P., Lu, X., Smith, E. C., Case, J. B., Feng, J. Y., Jordan, R., Ray, A. S., Cihlar, T., Siegel, D., Mackman, R. L., Clarke, M. O., Baric, R. S., & Denison, M. R. (2018). Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease. MBio, 9(2). https://doi.org/10.1128/mBio.00221-18

Keyaerts, E., Li, S., Vijgen, L., Rysman, E., Verbeeck, J., Van Ranst, M., & Maes, P. (2009). Antiviral activity of chloroquine against human coronavirus OC43 infection in newborn mice. Antimicrobial Agents and Chemotherapy, 53(8), 3416–3421. https://doi.org/10.1128/AAC.01509-08

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