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Synergistic activity of an RNA polymerase PA-PB1 interaction inhibitor with oseltamivir against human and avian influenza viruses in cell culture and in ovo.
- Source :
-
Antiviral research [Antiviral Res] 2024 Oct; Vol. 230, pp. 105980. Date of Electronic Publication: 2024 Aug 06. - Publication Year :
- 2024
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Abstract
- In search of novel therapeutic options to treat influenza virus (IV) infections, we previously identified a series of inhibitors that act by disrupting the interactions between the PA and PB1 subunits of the viral RNA polymerase. These compounds showed broad-spectrum antiviral activity against human influenza A and B viruses and a high barrier to the induction of drug resistance in vitro. In this short communication, we investigated the effects of combinations of the PA-PB1 interaction inhibitor 54 with oseltamivir carboxylate (OSC), zanamivir (ZA), favipiravir (FPV), and baloxavir marboxil (BXM) on the inhibition of influenza A and B virus replication in vitro. We observed a synergistic effect of the 54/OSC and 54/ZA combinations and an antagonistic effect when 54 was combined with either FPV or BXM. Moreover, we demonstrated the efficacy of 54 against highly pathogenic avian influenza viruses (HPAIVs) both in cell culture and in the embryonated chicken eggs model. Finally, we observed that 54 enhances OSC protective effect against HPAIV replication in the embryonated eggs model. Our findings represent an advance in the development of alternative therapeutic strategies against both human and avian IV infections.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024. Published by Elsevier B.V.)
- Subjects :
- Animals
Humans
Chick Embryo
Amides pharmacology
Dibenzothiepins pharmacology
Influenza B virus drug effects
Influenza B virus physiology
Zanamivir pharmacology
Triazines pharmacology
Pyridones pharmacology
Influenza in Birds drug therapy
Influenza in Birds virology
Morpholines pharmacology
Influenza, Human drug therapy
Influenza, Human virology
Dogs
DNA-Directed RNA Polymerases antagonists & inhibitors
DNA-Directed RNA Polymerases metabolism
RNA-Dependent RNA Polymerase antagonists & inhibitors
RNA-Dependent RNA Polymerase metabolism
Cell Line
Madin Darby Canine Kidney Cells
Oseltamivir pharmacology
Oseltamivir analogs & derivatives
Antiviral Agents pharmacology
Virus Replication drug effects
Drug Synergism
Pyrazines pharmacology
Influenza A virus drug effects
Viral Proteins metabolism
Viral Proteins antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9096
- Volume :
- 230
- Database :
- MEDLINE
- Journal :
- Antiviral research
- Publication Type :
- Academic Journal
- Accession number :
- 39117284
- Full Text :
- https://doi.org/10.1016/j.antiviral.2024.105980