Combination therapy protects macaques against advanced Marburg virus disease

Nat Commun. 2021 Mar 25;12(1):1891. doi: 10.1038/s41467-021-22132-0.

Abstract

Monoclonal antibodies (mAbs) and remdesivir, a small-molecule antiviral, are promising monotherapies for many viruses, including members of the genera Marburgvirus and Ebolavirus (family Filoviridae), and more recently, SARS-CoV-2. One of the major challenges of acute viral infections is the treatment of advanced disease. Thus, extending the window of therapeutic intervention is critical. Here, we explore the benefit of combination therapy with a mAb and remdesivir in a non-human primate model of Marburg virus (MARV) disease. While rhesus monkeys are protected against lethal infection when treatment with either a human mAb (MR186-YTE; 100%), or remdesivir (80%), is initiated 5 days post-inoculation (dpi) with MARV, no animals survive when either treatment is initiated alone beginning 6 dpi. However, by combining MR186-YTE with remdesivir beginning 6 dpi, significant protection (80%) is achieved, thereby extending the therapeutic window. These results suggest value in exploring combination therapy in patients presenting with advanced filovirus disease.

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
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Viral / therapeutic use*
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Macaca mulatta
  • Marburg Virus Disease / drug therapy*
  • Marburg Virus Disease / prevention & control
  • Marburgvirus / drug effects*
  • Viral Load / drug effects

Substances

  • Antibodies, Monoclonal
  • Antibodies, Viral
  • remdesivir
  • Adenosine Monophosphate
  • Alanine