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

  • Robert W. Cross
  • , Zachary A. Bornholdt
  • , Abhishek N. Prasad
  • , Courtney Woolsey
  • , 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
  • , Natalie S. Dobias
  • , Karla A. Fenton
  • , Danielle P. Porter
  • , Larry Zeitlin
  • , Thomas W. Geisbert

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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.

Original languageEnglish (US)
Article numbere159090
JournalJCI insight
Volume7
Issue number10
DOIs
StatePublished - May 23 2022

ASJC Scopus subject areas

  • General Medicine

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