Remdesivir is efficacious in rhesus monkeys exposed to aerosolized Ebola virus

Travis K Warren; Christopher D Kane; Jay Wells; Kelly S Stuthman; Sean A Van Tongeren; Nicole L Garza; Ginger Donnelly; Jesse Steffens; Laura Gomba; Jessica M Weidner; Sarah Norris; Xiankun Zeng; Roy Bannister; Tomas Cihlar; Sina Bavari; Danielle P Porter; Patrick L Iversen

doi:10.1038/s41598-021-98971-0

Remdesivir is efficacious in rhesus monkeys exposed to aerosolized Ebola virus

Sci Rep. 2021 Sep 30;11(1):19458. doi: 10.1038/s41598-021-98971-0.

Authors

Travis K Warren^{1

2

3}, Christopher D Kane^{1

4}, Jay Wells^{1

2}, Kelly S Stuthman^{1

2}, Sean A Van Tongeren^{1

2}, Nicole L Garza^{1

2

5}, Ginger Donnelly^{1

2}, Jesse Steffens^{1

2}, Laura Gomba^{1

2}, Jessica M Weidner^{1

2

6}, Sarah Norris^{1

2}, Xiankun Zeng⁷, Roy Bannister⁸, Tomas Cihlar⁸, Sina Bavari^{1

9}, Danielle P Porter⁸, Patrick L Iversen^{10

11}

Affiliations

¹ United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, 21702, USA.
² The Geneva Foundation, Tacoma, WA, 98402, USA.
³ Laulima Government Solutions, Integrated Research Facility NIAID/NIH, Fort Detrick, Frederick, MD, 21702, USA.
⁴ National Cancer Institute, Frederick, MD, 21702, USA.
⁵ SARS-CoV-2 Virology Core, LVD/NIAID/NIH, Bethesda, MD, 20892, USA.
⁶ Thomas Scientific, Swedesboro, NJ, 08085, USA.
⁷ United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, 21702, USA. xiankun.zeng.civ@mail.mil.
⁸ Gilead Sciences, Foster City, CA, 94404, USA.
⁹ , Helios, Frederick, MD, 21702, USA.
¹⁰ United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, 21702, USA. piversen@genevausa.org.
¹¹ The Geneva Foundation, Tacoma, WA, 98402, USA. piversen@genevausa.org.

Abstract

Efficacious therapeutics for Ebola virus disease are in great demand. Ebola virus infections mediated by mucosal exposure, and aerosolization in particular, present a novel challenge due to nontypical massive early infection of respiratory lymphoid tissues. We performed a randomized and blinded study to compare outcomes from vehicle-treated and remdesivir-treated rhesus monkeys in a lethal model of infection resulting from aerosolized Ebola virus exposure. Remdesivir treatment initiated 4 days after exposure was associated with a significant survival benefit, significant reduction in serum viral titer, and improvements in clinical pathology biomarker levels and lung histology compared to vehicle treatment. These observations indicate that remdesivir may have value in countering aerosol-induced Ebola virus disease.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adenosine Monophosphate / administration & dosage
Adenosine Monophosphate / analogs & derivatives*
Adenosine Monophosphate / pharmacology
Administration, Intravenous
Aerosols
Alanine / administration & dosage
Alanine / analogs & derivatives*
Alanine / pharmacology
Animals
Antiviral Agents / administration & dosage
Antiviral Agents / pharmacology*
Disease Models, Animal
Ebolavirus / drug effects*
Female
Hemorrhagic Fever, Ebola / blood
Hemorrhagic Fever, Ebola / drug therapy*
Kaplan-Meier Estimate
Liver / drug effects
Liver / virology
Lung / pathology
Lung / virology
Lymph Nodes / drug effects
Lymph Nodes / pathology
Lymph Nodes / virology
Macaca mulatta
Male
Random Allocation
Systemic Inflammatory Response Syndrome / drug therapy
Systemic Inflammatory Response Syndrome / virology
Viral Load / drug effects
Viremia / drug therapy

Substances

Aerosols
Antiviral Agents
remdesivir
Adenosine Monophosphate
Alanine

Grants and funding

W911QY-16-9-0001/US Army Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense Joint Project Manager for Chemical, Biological, Radiological, and Nuclear Defense Medical under