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

19 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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