During the Covid-19 pandemic, many drugs have been the subject of clinical trials without providing convincing evidence of efficacy against SARS-CoV-2. If the episode of hydroxychloroquine marked the general public, it is not the only molecule that has been the subject of an investigation by the scientific community regarding its potential effectiveness. Favipiravir, which was originally developed to treat severe influenza, is now used, especially in Asia, in the fight against Covid-19. Yet evidence of its effectiveness has so far been limited to tests in vitro and clinical studies that are difficult to interpret because of their size or risk of bias.
For several years, French scientists from the GEPC have been interested in favipiravir as a potential first-line weapon against new viruses, especially against viral hemorrhagic fevers such as Ebola or Lassa.
Based on this experience, the researchers investigated the antiviral activity of favipiravir against SARS-CoV-2 in animals by administering different doses of favipiravir or placebo to crab-eating macaques. This experimental model of infection is very useful because it makes it possible to reproduce a disease very similar to that observed in humans, and it had already made it possible to demonstrate the lack of effectiveness of hydroxychloroquine in a publication published in the journal Nature in 2020. In these new trials, no effect on viral load was observed in animals infected with SARS-CoV-2 and treated with favipiravir, including at high doses. Moreover, a debilitating development was even observed in four animals after the consumption of the molecule, whose condition worsened rapidly.
Following the same protocol, the researchers also tested the effectiveness of the drug against the Zika virus. Their results show that favipiravir this time leads to a significant reduction in the virus load in primates and thus underlines the potential interest of this molecule for this indication.
” This study again demonstrates the importance of rigorous evaluation of drugs in experimental models before their administration in humans. While the molecule has been tested in several clinical trials with results that are often difficult to interpret, our study unequivocally establishes the lack of antiviral efficacy of favipiravir against SARS-CoV-2. “, specifies Romain Marlin, co-first author of this study and project leader at the CEA, in charge of preclinical programs in immunotherapy and vaccinology (IDMIT, François Jacob Institute of Biology of the CEA). ” However, these results do not prejudge the activity of favipiravir against other viruses, as shown by our results on Zika virus. Studies on humans are underway with support from ANRS | New infectious diseases, to assess the potential of favipiravir in other indications, especially Lassa fever virus, for which we do not have an antiviral treatment explains Jérémie Guedj, Research Director at Inserm (IAE laboratory, Inserm / Paris Cité University / Sorbonne Paris Nord University), co-principal investigator of the study together with Roger Le Grand, Research Director at CEA (IDMIT, François Jacob Institute of Biology).
This study was funded by the Institute for Medical Research (FRM), the European Infrastructure TRANSVAC2, Auvergne-Rhône-Alpes Region, ANRS | Emerging Infectious Diseases (via the former REACTing consortium), the ZIKAlliance project, which received support from the EU’s Horizon 2020 research and innovation programme.
1 The preclinical study group (GEPC), which brings together specialists in animal models, virologists, clinicians, pharmacologists, biostatisticians, veterinarians, biochemists and model builders, among others, was set up by ANRS | New infectious diseases to evaluate (in non-human, in vitro or in vivo models) as rigorously as possible therapeutic candidates before trials in humans, prioritizing the most promising molecules.