Comparative Therapeutic Efficacy of Remdesivir and Combination Lopinavir, Ritonavir, and Interferon Beta Against MERS-CoV

Nat Commun. 2020 Jan 10;11(1):222. doi: 10.1038/s41467-019-13940-6.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Monophosphate / analogs & derivatives*
  • Adenosine Monophosphate / therapeutic use
  • Alanine / analogs & derivatives*
  • Alanine / therapeutic use
  • Animals
  • Antiviral Agents / therapeutic use
  • Carboxylesterase / genetics
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / pathology
  • Drug Combinations
  • Drug Development
  • Female
  • Humans
  • Interferon-beta / therapeutic use*
  • Lopinavir / therapeutic use*
  • Lung Injury / pathology
  • Male
  • Mice
  • Mice, Knockout
  • Middle East Respiratory Syndrome Coronavirus / drug effects*
  • Ritonavir / therapeutic use*
  • Viral Load
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Drug Combinations
  • lopinavir-ritonavir drug combination
  • Lopinavir
  • remdesivir
  • Adenosine Monophosphate
  • Interferon-beta
  • Carboxylesterase
  • Ces1c protein, mouse
  • Ritonavir
  • Alanine