Remdesivir As A Potential Broad-Spectrum Antiviral Drug
- 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
- 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).
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