Combination therapy protects macaques against advanced Marburg virus disease.

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.

• Authors: Robert W Cross, Zachary A Bornholdt, Abhishek N Prasad, Viktoriya Borisevich, Krystle N Agans, Daniel J Deer, Dafna M Abelson, Do H Kim, William S Shestowsky, Lioudmila A Campbell, Elaine Bunyan, Joan B Geisbert, Karla A Fenton, Larry Zeitlin, Danielle P Porter, Thomas W Geisbert
• Journal: Nature communications (Nat Commun) Vol. 12 Issue 1 Pg. 1891 (03 25 2021) ISSN: 2041-1723 [Electronic] England
• PMID: 33767178 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

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

Topics

• Adenosine Monophosphate (analogs & derivatives, therapeutic use)
• Alanine (analogs & derivatives, therapeutic use)
• Animals
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Viral (therapeutic use)
• Disease Models, Animal
• Drug Therapy, Combination
• Macaca mulatta
• Marburg Virus Disease (drug therapy, prevention & control)
• Marburgvirus (drug effects)
• Viral Load (drug effects)