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Lassa antiviral LHF-535 protects guinea pigs from lethal challenge
Kathleen A Cashman1, Eric R Wilkinson1, Jeffrey Posakony2,3
1Virology Division, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, USA.
Scientific Reports
|November 19, 2022
Summary
LHF-535, a novel antiviral, effectively treats Lassa fever in guinea pigs by reducing viral load and preventing death. Survivors demonstrated lasting immunity, supporting its potential as a Lassa fever therapeutic.
Area of Science:
- * Virology and infectious diseases
- * Drug development and pharmacology
Background:
- * Lassa fever is a severe zoonotic disease prevalent in West Africa with high mortality.
- * Existing treatments for Lassa fever are insufficient, and no approved vaccines are available.
- * There is a critical need for effective Lassa fever therapeutics.
Purpose of the Study:
- * To evaluate the efficacy of LHF-535, a small molecule antiviral, in a lethal guinea pig model of Lassa fever.
- * To assess the protective and immunogenic potential of LHF-535 treatment.
Main Methods:
- * Guinea pigs were inoculated with a lethal dose of Lassa virus.
- * LHF-535 (50 mg/kg/day) was administered once daily, starting 1 or 3 days post-inoculation.
- * Viremia, clinical signs, survival rates, and pharmacokinetic profiles were assessed. A subset of survivors was rechallenged four months later.
Main Results:
- * LHF-535 treatment significantly reduced Lassa virus viremia and clinical symptoms.
- * All treated animals survived the lethal Lassa virus challenge.
- * Surviving animals rechallenged four months later were protected, indicating durable immunity.
- * Pharmacokinetic data in guinea pigs supported concentrations observed in human clinical trials.
Conclusions:
- * LHF-535 demonstrates potent antiviral activity against Lassa virus in a preclinical model.
- * LHF-535 provides complete protection from mortality and induces a potentially long-lasting immune response.
- * The findings support the continued clinical development of LHF-535 as a promising therapeutic for Lassa fever.
