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

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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, 2020. "Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13940-6
    DOI: 10.1038/s41467-019-13940-6
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    Cited by:

    1. Tu, Yunbo & Meng, Xinzhu, 2023. "A reaction–diffusion epidemic model with virus mutation and media coverage: Theoretical analysis and numerical simulation," Mathematics and Computers in Simulation (MATCOM), Elsevier, vol. 214(C), pages 28-67.
    2. Jacob A. Dillard & Sharon A. Taft-Benz & Audrey C. Knight & Elizabeth J. Anderson & Katia D. Pressey & Breantié Parotti & Sabian A. Martinez & Jennifer L. Diaz & Sanjay Sarkar & Emily A. Madden & Gabr, 2024. "Adjuvant-dependent impact of inactivated SARS-CoV-2 vaccines during heterologous infection by a SARS-related coronavirus," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. Joseph F. Standing & Laura Buggiotti & Jose Afonso Guerra-Assuncao & Maximillian Woodall & Samuel Ellis & Akosua A. Agyeman & Charles Miller & Mercy Okechukwu & Emily Kirkpatrick & Amy I. Jacobs & Cha, 2024. "Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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