title: The broad-spectrum antiviral favipiravir protects guinea pigs from lethal Lassa virus infection post-disease onset.
abstract: With up to 500,000 infections annually, Lassa virus (LASV), the cause of Lassa fever, is one of the most prevalent etiological agents of viral hemorrhagic fever (VHF) in humans. LASV is endemic in several West African countries with sporadic cases and prolonged outbreaks observed most commonly in Sierra Leone, Liberia, Guinea and Nigeria. Additionally several cases of Lassa fever have been imported into North America, Europe and Asia making LASV a global threat to public health. Despite this, currently no approved therapeutic or vaccine exists to treat or prevent LASV infections. Here, using a passaged strain of LASV that is uniformly lethal in Hartley guinea pigs, we demonstrate that favipiravir, a broad-spectrum antiviral agent and leading treatment option for influenza, has potent activity against LASV infection. In this model, once daily treatment with favipiravir significantly reduced viral titers in tissue samples and reduced mortality rates when compared with animals receiving vehicle-only or ribavirin, the current standard of care for Lassa fever. Favipiravir remained highly effective against lethal LASV infection when treatments were initiated nine days post-infection, a time when animals were demonstrating advanced signs of disease. These results support the further preclinical evaluation of favipiravir for Lassa fever and other VHFs.
authors.affiliation: Laboratory of Virology, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Safronetz
authors.affiliation: Laboratory of Virology, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
authors.forename: Kyle
authors.initials: K
authors.lastname: Rosenke
authors.affiliation: Department of Animal, Diary, and Veterinary Sciences, Utah State University, Logan, Utah, United States of America.
authors.forename: Jonna B
authors.initials: JB
authors.lastname: Westover
authors.affiliation: Laboratory of Virology, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Martellaro
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okumura
authors.affiliation: Research Laboratories, Toyama Chemical Co., Ltd. Toyama, Japan.
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Furuta
authors.affiliation: Galveston National Laboratory and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Joan
authors.initials: J
authors.lastname: Geisbert
authors.affiliation: Rocky Mountain Veterinary Branch, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
authors.forename: Greg
authors.initials: G
authors.lastname: Saturday
authors.affiliation: Research Laboratories, Toyama Chemical Co., Ltd. Toyama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Komeno
authors.affiliation: Galveston National Laboratory and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Geisbert
authors.affiliation: Laboratory of Virology, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
authors.affiliation: Department of Animal, Diary, and Veterinary Sciences, Utah State University, Logan, Utah, United States of America.
authors.forename: Brian B
authors.initials: BB
authors.lastname: Gowen
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000818:Animals; D021461:Animals, Outbred Strains; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000097:blood; D000998:Antiviral Agents / Q000494:pharmacology*; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D006168:Guinea Pigs; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000097:blood; D007835:Lassa Fever / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000821:virology; D007836:Lassa virus / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000821:virology; D008168:Lung / Q000187:drug effects / Q000821:virology; D008297:Male; D011719:Pyrazines / Q000494:pharmacology*; D012254:Ribavirin / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects / Q000473:pathology / Q000821:virology; D016019:Survival Analysis; D019562:Viral Load / Q000187:drug effects
chemical_list: D000577:Amides; D000914:Antibodies, Viral; D000998:Antiviral Agents; D007074:Immunoglobulin G; D011719:Pyrazines; D012254:Ribavirin; C462182:favipiravir