Favipiravir at high doses has potent antiviral activity in SARS-CoV-2-infected hamsters, whereas hydroxychloroquine lacks activity

Kaptein Suzanne J. F.; Jacobs Sofie; Langendries LanaSeldeslachts Laurater Horst SebastiaanLiesenborghs LaurensHens BartVergote ValentijnHeylen ElisabethBarthelemy KarineMaas ElkeDe Keyzer CarolienBervoets LindseyRymenants JasperVan Buyten TinaZhang XinAbdelnabi RanaPang JuanitaWilliams RachelThibaut Hendrik JanDallmeier KaiBoudewijns RobbertWouters JensAugustijns PatrickVerougstraete NickCawthorne ChristopherBreuer JudithSolas CarolineWeynand BirgitAnnaert PieterSpriet IsabelVande Velde GreetjeNeyts JohanRocha-Pereira JoanaDelang Leen

首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America. >Favipiravir at high doses has potent antiviral activity in SARS-CoV-2-infected hamsters, whereas hydroxychloroquine lacks activity

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Favipiravir at high doses has potent antiviral activity in SARS-CoV-2-infected hamsters, whereas hydroxychloroquine lacks activity

机译：Favipiravir at high doses has potent antiviral activity in SARS-CoV-2-infected hamsters, whereas hydroxychloroquine lacks activity

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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.

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《Proceedings of the National Academy of Sciences of the United States of America.》 |2020年第43期|26955-26965|共11页
作者
Kaptein Suzanne J. F.; Jacobs Sofie; Langendries LanaSeldeslachts Laurater Horst SebastiaanLiesenborghs LaurensHens BartVergote ValentijnHeylen ElisabethBarthelemy KarineMaas ElkeDe Keyzer CarolienBervoets LindseyRymenants JasperVan Buyten TinaZhang XinAbdelnabi RanaPang JuanitaWilliams RachelThibaut Hendrik JanDallmeier KaiBoudewijns RobbertWouters JensAugustijns PatrickVerougstraete NickCawthorne ChristopherBreuer JudithSolas CarolineWeynand BirgitAnnaert PieterSpriet IsabelVande Velde GreetjeNeyts JohanRocha-Pereira JoanaDelang Leen;
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作者单位

Lab Virol & Chemotherapy,Katholieke Univ Leuven;

Biomed MRI & Mol Small Anim Imaging Ctr,Katholieke Univ Leuven;

Drug Delivery & Disposit,Katholieke Univ LeuvenUnite Virus Emergents,Aix Marseille UnivUCL Great Ormond St Inst Child Hlth,UCLDept Imaging & Pathol,Katholieke Univ LeuvenDept Lab Med,Ghent Univ HospAssistance Publ Hop Marseille,Aix Marseille UnivPharm Dept,Univ Hosp Leuven;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
antiviral therapy; SARS-CoV-2; preclinical model; favipiravir; hydroxychloroquine; RESPIRATORY SYNDROME CORONAVIRUS; FEVER VIRUS-INFECTION; COMPOUND; COVID-19; DISEASE; T-705;

Favipiravir at high doses has potent antiviral activity in SARS-CoV-2-infected hamsters, whereas hydroxychloroquine lacks activity

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