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Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV.

Authors :
Sheahan, Timothy P.
Sims, Amy C.
Leist, Sarah R.
Schäfer, Alexandra
Won, John
Brown, Ariane J.
Montgomery, Stephanie A.
Hogg, Alison
Babusis, Darius
Clarke, Michael O.
Spahn, Jamie E.
Bauer, Laura
Sellers, Scott
Porter, Danielle
Feng, Joy Y.
Cihlar, Tomas
Jordan, Robert
Denison, Mark R.
Baric, Ralph S.
Source :
Nature Communications; 1/10/2020, Vol. 11 Issue 1, p1-14, 14p
Publication Year :
2020

Abstract

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20411723
Volume :
11
Issue :
1
Database :
Complementary Index
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
141150704
Full Text :
https://doi.org/10.1038/s41467-019-13940-6