Drugs for the treatment of COVID-19, as well as for the prevention of infections after exposure to SARS-CoV-2, are interesting research targets. Richard Leduc, Université de Sherbrooke, Canada, Hector C. Aguilar, Cornell University, Ithaca, NY, USA, François Jean, University of British Columbia, Vancouver, Canada, and colleagues have found a small molecule, called N-0385, that could be used in nasal sprays to prevent COVID-19 or provide early treatment.
N-0385 is a peptidomimetic compound with the sequence Ms-Gln-Phe-Arg-kbt (Ms = mesyl, Gln = glutamine, Phe = phenylalanine, Arg = arginine, kbt = ketobenzothiazol). The drug targets the enzyme TMPRSS2 (transmembrane protease serine 2), which is important for cell entry.
The team tested N-0385 in mice that are engineered to express human receptors for the coronavirus on their cell surfaces. They introduced the compound intranasally into the mice before, during, and/or after exposure. They tracked the mice’s weight, temperature, and mortality, and performed tissue analyses. The researchers found that N-0385 inhibits entry of the virus into cells and protects mice from infection prior to exposure, while also providing effective treatment when administered up to 12 hours after exposure.
The treatment shows promise for both preventing COVID-19 and reducing the severity of the disease post-infection with a few single daily doses. The drug candidate was tested in mice exposed to the “original” strain of SARS-CoV-2, as well as the delta variant, but has not been tested with the omicron variant. Human trials will need to be performed next.
- A TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and therapeutic,
Tirosh Shapira, I. Abrrey Monreal, Sébastien P. Dion, David W. Buchholz, Brian Imbiakha, Andrea D. Olmstead, Mason Jager, Antoine Désilets, Guang Gao, Mathias Martins, Thierry Vandal, Connor A. H. Thompson, Aaleigha Chin, William D. Rees, Theodore Steiner, Ivan Robert Nabi, Eric Marsault, Julie Sahler, Diego G. Diel, Gerlinde R. Van de Walle, Avery August, Gary R. Whittaker, Pierre-Luc Boudreault, Richard Leduc, Hector C. Aguilar, François Jean,
Nature 2022.
https://doi.org/10.1038/s41586-022-04661-w
Also of Interest
- Collection: SARS-CoV-2 Virus
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