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

Timothy P. Sheahan (), Amy C. Sims, Sarah R. Leist, Alexandra Schäfer, John Won, Ariane J. Brown, Stephanie A. Montgomery, Alison Hogg, Darius Babusis, Michael O. Clarke, Jamie E. Spahn, Laura Bauer, Scott Sellers, Danielle Porter, Joy Y. Feng, Tomas Cihlar, Robert Jordan, Mark R. Denison and Ralph S. Baric ()
Additional contact information
Timothy P. Sheahan: University of North Carolina at Chapel Hill
Amy C. Sims: University of North Carolina at Chapel Hill
Sarah R. Leist: University of North Carolina at Chapel Hill
Alexandra Schäfer: University of North Carolina at Chapel Hill
John Won: University of North Carolina at Chapel Hill
Ariane J. Brown: University of North Carolina at Chapel Hill
Stephanie A. Montgomery: University of North Carolina
Alison Hogg: Gilead Sciences, Inc
Darius Babusis: Gilead Sciences, Inc
Michael O. Clarke: Gilead Sciences, Inc
Jamie E. Spahn: Gilead Sciences, Inc
Laura Bauer: Gilead Sciences, Inc
Scott Sellers: Gilead Sciences, Inc
Danielle Porter: Gilead Sciences, Inc
Joy Y. Feng: Gilead Sciences, Inc
Tomas Cihlar: Gilead Sciences, Inc
Robert Jordan: Gilead Sciences, Inc
Mark R. Denison: Vanderbilt University Medical Center
Ralph S. Baric: University of North Carolina at Chapel Hill

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-019-13940-6

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