Combination therapy with remdesivir and monoclonal antibodies protects nonhuman primates against advanced Sudan virus disease

JCI Insight. 2022 May 23;7(10):e159090. doi: 10.1172/jci.insight.159090.

Abstract

A major challenge in managing acute viral infections is ameliorating disease when treatment is delayed. Previously, we reported the success of a 2-pronged mAb and antiviral remdesivir therapeutic approach to treat advanced illness in rhesus monkeys infected with Marburg virus (MARV). Here, we explored the benefit of a similar combination therapy for Sudan ebolavirus (Sudan virus; SUDV) infection. Importantly, no licensed anti-SUDV therapeutics currently exist, and infection of rhesus macaques with SUDV results in a rapid disease course similar to MARV with a mean time to death of 8.3 days. When initiation of therapy with either remdesivir or a pan-ebolavirus mAb cocktail (MBP431) was delayed until 6 days after inoculation, only 20% of macaques survived. In contrast, when remdesivir and MBP431 treatment were combined beginning 6 days after inoculation, significant protection (80%) was achieved. Our results suggest that combination therapy may be a viable treatment for patients with advanced filovirus disease that warrants further clinical testing in future outbreaks.

Keywords: Immunotherapy; Virology.

Publication types

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

MeSH terms

  • Adenosine Monophosphate / analogs & derivatives
  • Alanine / analogs & derivatives
  • Animals
  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Ebolavirus*
  • Hemorrhagic Fever, Ebola* / drug therapy
  • Hemorrhagic Fever, Ebola* / prevention & control
  • Humans
  • Macaca mulatta
  • Marburgvirus*
  • Virus Diseases*

Substances

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