Lassa antiviral LHF-535 protects guinea pigs from lethal challenge.

Autor: Cashman KA; Virology Division, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, USA., Wilkinson ER; Virology Division, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, USA., Posakony J; Kineta, Inc., Seattle, WA, USA.; AltPep, Seattle, WA, USA., Madu IG; Kineta, Inc., Seattle, WA, USA.; Lyell Immunopharma, Seattle, WA, USA., Tarcha EJ; Kineta, Inc., Seattle, WA, USA., Lustig KH; Kineta, Inc., Seattle, WA, USA., Korth MJ; Kineta, Inc., Seattle, WA, USA., Bedard KM; Kineta, Inc., Seattle, WA, USA.; Sutro Biopharma, South San Francisco, CA, USA., Amberg SM; Kineta, Inc., Seattle, WA, USA. SAmberg@kineta.us.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Nov 19; Vol. 12 (1), pp. 19911. Date of Electronic Publication: 2022 Nov 19.
DOI: 10.1038/s41598-022-23760-2
Abstrakt: LHF-535 is a small molecule antiviral currently in development for the treatment of Lassa fever, a zoonotic disease endemic in West Africa that generates significant morbidity and mortality. Current treatment options are inadequate, and there are no approved therapeutics or vaccines for Lassa fever. LHF-535 was evaluated in a lethal guinea pig model of Lassa pathogenesis, using once-daily administration of a fixed dose (50 mg/kg/day) initiating either 1 or 3 days after inoculation with a lethal dose of Lassa virus. LHF-535 reduced viremia and clinical signs and protected all animals from lethality. A subset of surviving animals was rechallenged four months later with a second lethal challenge of Lassa virus and were found to be protected from disease. LHF-535 pharmacokinetics at the protective dose in guinea pigs showed plasma concentrations well within the range observed in clinical trials in healthy volunteers, supporting the continued development of LHF-535 as a Lassa therapeutic.
(© 2022. The Author(s).)
Databáze: MEDLINE
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