Ebola virus disease: In vivo protection provided by the PAMP restricted TLR3 agonist rintatolimod and its mechanism of action

Antiviral Res. 2023 Apr:212:105554. doi: 10.1016/j.antiviral.2023.105554. Epub 2023 Feb 16.

Abstract

Ebola virus (EBOV) is a highly infectious and lethal pathogen responsible for sporadic self-limiting clusters of Ebola virus disease (EVD) in Central Africa capable of reaching epidemic status. 100% protection from lethal EBOV-Zaire in Balb/c mice was achieved by rintatolimod (Ampligen) at the well tolerated human clinical dose of 6 mg/kg. The data indicate that the mechanism of action is rintatolimod's dual ability to act as both a competitive decoy for the IID domain of VP35 blocking viral dsRNA sequestration and as a pathogen-associated molecular pattern (PAMP) restricted agonist for direct TLR3 activation but lacking RIG-1-like cytosolic helicase agonist properties. These data show promise for rintatolimod as a prophylactic therapy against human Ebola outbreaks.

Keywords: EBOV Lethal factor; Ebola virus (EBOV); PAMP-Restricted TLR3 agonist; Rintatolimod (Ampligen); Type I Interferons; VP35.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ebolavirus* / genetics
  • Hemorrhagic Fever, Ebola* / drug therapy
  • Hemorrhagic Fever, Ebola* / prevention & control
  • Humans
  • Mice
  • Poly I-C
  • Toll-Like Receptor 3
  • Viral Regulatory and Accessory Proteins

Substances

  • poly(I).poly(c12,U)
  • Toll-Like Receptor 3
  • Viral Regulatory and Accessory Proteins
  • Poly I-C
  • TLR3 protein, human
  • TLR3 protein, mouse