دورية أكاديمية
Coadministration of LHF-535 and favipiravir protects against experimental Junín virus infection and disease.
| العنوان: | Coadministration of LHF-535 and favipiravir protects against experimental Junín virus infection and disease. |
|---|---|
| المؤلفون: | Westover JB; Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT, USA., Bailey KW; Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT, USA., Wasson SR; Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT, USA., Boardman KM; Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT, USA., Lustig KH; Kineta, Inc., Seattle, WA, USA., Amberg SM; Kineta, Inc., Seattle, WA, USA., Gowen BB; Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT, USA. Electronic address: brian.gowen@usu.edu. |
| المصدر: | Antiviral research [Antiviral Res] 2024 Sep; Vol. 229, pp. 105952. Date of Electronic Publication: 2024 Jun 28. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8109699 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-9096 (Electronic) Linking ISSN: 01663542 NLM ISO Abbreviation: Antiviral Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Amsterdam : Elsevier Original Publication: [Amsterdam ; New York : Elsevier/North-Holland Biomedical Press, c1981- |
| مواضيع طبية MeSH: | Pyrazines*/pharmacology , Pyrazines*/administration & dosage , Pyrazines*/therapeutic use , Amides*/pharmacology , Amides*/therapeutic use , Amides*/administration & dosage , Junin virus*/drug effects , Antiviral Agents*/pharmacology , Antiviral Agents*/administration & dosage , Antiviral Agents*/therapeutic use , Disease Models, Animal*, Animals ; Guinea Pigs ; Hemorrhagic Fever, American/drug therapy ; Hemorrhagic Fever, American/virology ; Drug Therapy, Combination ; Female ; Drug Synergism ; Arenaviridae Infections/drug therapy |
| مستخلص: | Argentine hemorrhagic fever, caused by Junín virus (JUNV), is the most common of the South American arenaviral hemorrhagic fevers. The disease has a case fatality rate of 15-30% in untreated patients. Although early intervention with immune plasma is effective, diminishing stocks and limited availability outside of Argentina underscores the need for new therapeutics. Ideally, these would be broadly active agents effective against all the pathogenic arenaviruses. The fusion inhibitor LHF-535 and the nucleoside analog favipiravir have shown promise in animal models of Lassa fever, a disease endemic in parts of Africa and the most prominent of the arenaviral hemorrhagic fevers. Against JUNV, a high dose of favipiravir is required to achieve protection in the gold-standard guinea pig infection model. Here, we demonstrate a synergistic effect by the coadministration of LHF-535 with a sub-optimal dose of favipiravir in guinea pigs challenged with JUNV. Administered individually, LHF-535 and sub-optimal favipiravir only delayed the onset of severe disease. However, combined dosing of the drugs afforded complete protection against lethal JUNV infection in guinea pigs. The benefits of the drug combination were also evident by the absence of viremia and infectious virus in tissues compared to guinea pigs treated with only the placebos. Thus, combined targeting of JUNV-endosomal membrane fusion and the viral polymerase with pan-arenaviral LHF-535 and favipiravir may expand their indication beyond Lassa fever, providing a significant barrier to drug resistance. Competing Interests: Declaration of competing interest K.H.L. is/S.M.A. was employed by Kineta, Inc., the company developing LHF-535 to treat Lassa fever. All other authors declare no competing interests. (Copyright © 2024 Elsevier B.V. All rights reserved.) |
| References: | Antiviral Res. 2016 Feb;126:62-8. (PMID: 26711718) Antiviral Res. 2018 Nov;159:63-67. (PMID: 30261226) PLoS Pathog. 2018 Dec 21;14(12):e1007439. (PMID: 30576397) Emerg Infect Dis. 2020 Jul;26(7):1562-1566. (PMID: 32271701) Emerg Infect Dis. 2020 Jun;26(6):1332-1334. (PMID: 32441627) PLoS Pathog. 2009 May;5(5):e1000455. (PMID: 19478873) Antiviral Res. 2017 Sep;145:131-135. (PMID: 28780425) FASEB J. 2008 Mar;22(3):659-61. (PMID: 17942826) PLoS Negl Trop Dis. 2013 Dec 26;7(12):e2614. (PMID: 24386500) Antiviral Res. 2008 Apr;78(1):132-9. (PMID: 18054395) Travel Med Infect Dis. 2020 Jul - Aug;36:101589. (PMID: 32061859) Nat Rev Microbiol. 2023 Feb;21(2):87-96. (PMID: 36097163) Antiviral Res. 2022 Dec;208:105444. (PMID: 36243175) Antimicrob Agents Chemother. 2022 Nov 15;66(11):e0095122. (PMID: 36314868) Sci Rep. 2022 Nov 19;12(1):19911. (PMID: 36402782) Sci Rep. 2015 Oct 12;5:14775. (PMID: 26456301) |
| معلومات مُعتمدة: | R01 AI141102 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: Arenavirus; Favipiravir; Junín virus; LHF-535; Lassa virus; Mammarenavirus |
| المشرفين على المادة: | 0 (Pyrazines) EW5GL2X7E0 (favipiravir) 0 (Amides) 0 (Antiviral Agents) |
| تواريخ الأحداث: | Date Created: 20240630 Date Completed: 20240812 Latest Revision: 20240923 |
| رمز التحديث: | 20240923 |
| مُعرف محوري في PubMed: | PMC11323185 |
| DOI: | 10.1016/j.antiviral.2024.105952 |
| PMID: | 38945484 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1872-9096 |
|---|---|
| DOI: | 10.1016/j.antiviral.2024.105952 |