Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV
| Autor: | John J. Won, Michael O'neil Hanrahan Clarke, Alison Hogg, Ralph S. Baric, Mark R. Denison, Tomas Cihlar, Darius Babusis, Timothy P. Sheahan, Joy Y. Feng, Ariane J. Brown, Sarah R. Leist, Danielle P. Porter, Bauer Laura Elizabeth, Alexandra Schäfer, Jamie E. Spahn, Stephanie A. Montgomery, Amy C. Sims, Robert Jordan, Scott P. Sellers |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine viruses Lopinavir/ritonavir General Physics and Astronomy Virus Replication medicine.disease_cause Lopinavir Carboxylesterase Pulmonary function testing Mice 0302 clinical medicine immune system diseases Medicine 030212 general & internal medicine lcsh:Science Mice Knockout Alanine Multidisciplinary Respiratory disease virus diseases Lung Injury Viral Load 3. Good health Drug Combinations Middle East Respiratory Syndrome Coronavirus Antiviral agents COVID-19 Viral pathogenesis Viral infection Drug development Female Coronavirus Infections Viral load medicine.drug Middle East respiratory syndrome coronavirus Science Lung injury Antiviral Agents Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Animals Humans Ritonavir business.industry Interferon-beta General Chemistry medicine.disease Virology Adenosine Monophosphate 030104 developmental biology lcsh:Q business |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-14 (2020) Nature Communications Nature Communications, 11:222 |
| ISSN: | 2041-1723 |
| Popis: | Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in the Kingdom of Saudi Arabia. Here, we show that remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improve pulmonary function and reduce lung viral loads and severe lung pathology. In contrast, prophylactic LPV/RTV-IFNb slightly reduces viral loads without impacting other disease parameters. Therapeutic LPV/RTV-IFNb improves pulmonary function but does not reduce virus replication or severe lung pathology. Thus, we provide in vivo evidence of the potential for RDV to treat MERS-CoV infections. Remdesivir (RDV) is a broad-spectrum antiviral drug with activity against MERS coronavirus, but in vivo efficacy has not been evaluated. Here, the authors show that RDV has superior anti-MERS activity in vitro and in vivo compared to combination therapy with lopinavir, ritonavir and interferon beta and reduces severe lung pathology. |
| Databáze: | OpenAIRE |
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