In vitro and in vivo efficacy of a novel nucleoside analog H44 against Crimean-Congo hemorrhagic fever virus.

Abstract

Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic tick-borne virus that causes fever, hemorrhage, and multi-organ failure, with an average fatality rate of ∼40% in humans. Currently, there are no available vaccines or drugs for the treatment of Crimean-Congo hemorrhagic fever (CCHF). Favipiravir (T-705), a nucleoside analog, protects against CCHFV infection in animal models. Here, we evaluated the anti-CCHFV efficacy of several nucleoside analogs, including some well-known compounds such as remdesivir (GS-5734), EIDD-1931 and its prodrug molnupiravir (EIDD-2801), as well as a novel T-705-derived compound H44. T-705, H44, and EIDD-1931 inhibited CCHFV infection in vitro while GS-5734 had no inhibitory effect. All three nucleoside analogs functioned at the "post-entry" stage of virus infection. However, EIDD-2801 failed to protect type I interferon receptor knockout (IFNAR)-/- mice from CCHFV infection. H44, similar to T-705, conferred 100% protection to IFNAR-/- mice against lethal CCHFV challenge, even with delayed administration. This study provided in vitro and in vivo data regarding the anti-CCHFV efficacy of different nucleosides and identified a novel compound, H44, as a promising drug candidate for the treatment of CCHFV infection in vivo.

• Authors: Qianran Wang, Ruiyuan Cao, Liushuai Li, Jia Liu, Jingjing Yang, Wei Li, Linjie Yan, Yanming Wang, Yunzheng Yan, Jiang Li, Fei Deng, Yiwu Zhou, Manli Wang, Wu Zhong, Zhihong Hu
• Journal: Antiviral research (Antiviral Res) Vol. 199 Pg. 105273 (03 2022) ISSN: 1872-9096 [Electronic] Netherlands
• PMID: 35257725 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• Nucleosides

Topics

• Animals
• Disease Models, Animal
• Hemorrhagic Fever Virus, Crimean-Congo
• Hemorrhagic Fever, Crimean (drug therapy, prevention & control)
• Mice
• Nucleosides (pharmacology, therapeutic use)