Persistence of an infectious form of SARS-CoV-2 post protease inhibitor treatment of permissive cells in vitro.

Autor:	Nair MS; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA.; Division of Infectious Diseases, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA., Luck MI; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA.; Division of Infectious Diseases, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA., Huang Y; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA.; Division of Infectious Diseases, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA., Sabo Y; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA.; Division of Infectious Diseases, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA., Ho DD; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA.; Division of Infectious Diseases, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA.; Department of Microbiology and Immunology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA.; Lead contact.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2024 Aug 12. Date of Electronic Publication: 2024 Aug 12.
DOI:	10.1093/infdis/jiae385
Abstrakt:	Reports have described SARS-CoV-2 rebound in COVID-19 patients treated with nirmatrelvir, a 3CL protease inhibitor. The cause remains a mystery, although drug resistance, re-infection, and lack of adequate immune responses have been excluded. We now present virologic findings that provide a clue to the cause of viral rebound, which occurs in ∼20% of the treated cases. Persistence of infectious SARS-CoV-2 was experimentally documented in vitro after treatment with nirmatrelvir or another 3CL protease inhibitor, but not with a polymerase inhibitor, remdesivir. This infectious form decayed slowly with a half-life of ∼1 day, suggesting that its persistence could outlive the treatment course to re-ignite SARS-CoV-2 infection as the drug is eliminated. Notably, extending nirmatrelvir treatment beyond 8 days abolished viral rebound in vitro. Our findings point in a particular direction for future investigation of virus persistence and offer a specific treatment recommendation that should be tested clinically. (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
Databáze:	MEDLINE
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