The broad-spectrum antiviral favipiravir protects guinea pigs from lethal Lassa virus infection post-disease onset.

David Safronetz,Kyle Rosenke,Thomas W Geisbert,Heinz Feldmann,Cynthia Martellaro,Brian B Gowen,Jonna B Westover,Joan Geisbert,Greg Saturday,Yousuke Furuta,Takashi Komeno,Atsushi Okumura

doi:10.1038/srep14775

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.

Highlights

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
Analysis of infectious LASV titers (TCID50) in supernatants collected at day 3 and 5 post-infection from Vero cell cultures treated with varying concentrations of favipiravir resulted in EC90 values of 1.7 and 11.1 μ g/ ml, respectively
A limitation to evaluating potential therapeutics against LASV infection or Lassa fever (LF) disease is lack of readily available rodent models which can be utilized in initial efficacy studies

Summary

Introduction

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. 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. Viral hemorrhagic fevers (VHFs) are among the most deadly and feared group of diseases in humans and for most no approved vaccine or treatment exists[1]. Cases of LF are most commonly observed in Sierra Leona, Liberia, Guinea and Nigeria These four countries represent the regions historically considered endemic for LASV/LF; though it is becoming increasingly clear that other West African nations, including Mali, Cote d’Ivoire, Benin and Ghana are at risk for sporadic cases and potentially explosive outbreaks of LF7–10. Ribavirin therapy has been shown to reduce the morbidity and mortality associated with LF, its limited efficacy is reliant on treatment initiation within 6 days of disease onset[12]

Methods

Results

Conclusion