JCI Insight (May 2022)

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

Journal volume & issue
Vol. 7, no. 10

Abstract

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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.

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