ProcCluster ® and procaine hydrochloride inhibit the replication of influenza A virus in vitro .

Autor: Häring C; Section of Experimental Virology, Institute of Medical Microbiology, Center for Molecular Biomedicine (CMB), Jena University Hospital, Jena, Germany., Schroeder J; Section of Experimental Virology, Institute of Medical Microbiology, Center for Molecular Biomedicine (CMB), Jena University Hospital, Jena, Germany., Jungwirth J; Section of Experimental Virology, Institute of Medical Microbiology, Center for Molecular Biomedicine (CMB), Jena University Hospital, Jena, Germany., Löffler B; Institute of Medical Microbiology, Jena University Hospital, Jena, Germany., Henke A; Section of Experimental Virology, Institute of Medical Microbiology, Center for Molecular Biomedicine (CMB), Jena University Hospital, Jena, Germany., Engert B; inflamed pharma GmbH, Jena, Germany., Ehrhardt C; Section of Experimental Virology, Institute of Medical Microbiology, Center for Molecular Biomedicine (CMB), Jena University Hospital, Jena, Germany.
Jazyk: angličtina
Zdroj: Frontiers in microbiology [Front Microbiol] 2024 Aug 14; Vol. 15, pp. 1422651. Date of Electronic Publication: 2024 Aug 14 (Print Publication: 2024).
DOI: 10.3389/fmicb.2024.1422651
Abstrakt: Introduction: Treatment of influenza A virus infections is currently limited to few direct acting antiviral substances. Repurposing other established pharmaceuticals as antivirals could aid in improving treatment options.
Methods: This study investigates the antiviral properties of ProcCluster ® and procaine hydrochloride, two derivatives of the local anesthetic procaine, in influenza A virus infection of A549, Calu-3 and MDCK cells.
Results: Both substances inhibit replication in all three of these cell lines in multi-cycle experiments. However, cell line-dependent differences in the effects of the substances on viral RNA replication and subsequent protein synthesis, as well as release of progeny viruses in single-cycle experiments can be observed. Both ProcCluster ® and procaine hydrochloride delay endosome fusion of the virus early in the replication cycle, possibly due to the alkaline nature of the active component procaine. In A549 and Calu-3 cells an additional effect of the substances can be observed at late stages in the first replication cycle. Interestingly, this effect is absent in MDCK cells. We demonstrate that ProcCluster ® and procaine hydrochloride inhibit phospholipase A 2 (PLA 2 ) enzymes from A549 but not MDCK cells and confirm that specific inhibition of calcium independent PLA 2 but not cytosolic PLA 2 has antiviral effects.
Discussion: We show that ProcCluster ® and procaine hydrochloride inhibit influenza A virus infection at several stages of the replication cycle and have potential as antiviral substances.
Competing Interests: BE is employed by inflamed pharma GmbH which manufactured and provided ProcCluster®. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Häring, Schroeder, Jungwirth, Löffler, Henke, Engert and Ehrhardt.)
Databáze: MEDLINE
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