期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 43, 页码 26955-26965出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2014441117
关键词
antiviral therapy; SARS-CoV-2; preclinical model; favipiravir; hydroxychloroquine
资金
- European Union [101003627]
- Bill and Melinda Gates Foundation [INV-00636]
- Stichting Antoine Faes
- KU Leuven Internal Funds [C24/17/061]
- James Black charitable foundation [559133]
- FWO [1001719N]
- Fund for Scientific Research Flanders (FWO) [1S21918N, G0G4820N]
- KU Leuven internal project
- Rosetrees studentship [M876]
- National Institute for Health Research University College London/University College London Hospitals Biomedical Research Centre
- Covid-19-Fund KU Leuven/Universitair Ziekenhuis Leuven
- Flemish Research Council (FWO) [12R2119N]
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread around the globe after its emergence in Wuhan in December 2019. With no specific therapeutic and prophylactic options available, the virus has infected millions of people of which more than half a million succumbed to the viral disease, COVID-19. The urgent need for an effective treatment together with a lack of small animal infection models has led to clinical trials using repurposed drugs without preclinical evidence of their in vivo efficacy. We established an infection model in Syrian hamsters to evaluate the efficacy of small molecules on both infection and transmission. Treatment of SARS-CoV-2-infected hamsters with a low dose of favipiravir or hydroxychloroquine with(out) azithromycin resulted in, respectively, a mild or no reduction in virus levels. However, high doses of favipiravir significantly reduced infectious virus titers in the lungs and markedly improved lung histopathology. Moreover, a high dose of favipiravir decreased virus transmission by direct contact, whereas hydroxychloroquine failed as prophylaxis. Pharmacokinetic modeling of hydroxychloroquine suggested that the total lung exposure to the drug did not cause the failure. Our data on hydroxychloroquine (together with previous reports in macaques and ferrets) thus provide no scientific basis for the use of this drug in COVID-19 patients. In contrast, the results with favipiravir demonstrate that an antiviral drug at nontoxic doses exhibits a marked protective effect against SARS-CoV-2 in a small animal model. Clinical studies are required to assess whether a similar antiviral effect is achievable in humans without toxic effects.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据