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J Med Virol
. 2025 Apr;97(4):e70319.
doi: 10.1002/jmv.70319. Papaverine Targets STAT Signaling: A Dual-Action Therapy Option Against SARS-CoV-2
Philipp Reus 1 2 , Emma Torbica 2 , Tamara Rothenburger 2 , Marco Bechtel 2 , Joshua Kandler 2 , Sandra Ciesek 2 3 , Philip Gribbon 1 , Aimo Kannt 3 , Jindrich Cinatl 2 4 , Denisa Bojkova 2
Affiliations
Papaverine (PV) has been previously identified as a promising candidate in SARS-CoV-2 repurposing screens. In this study, we further investigated both its antiviral and immunomodulatory properties. PV displayed antiviral efficacy against SARS-CoV-2 and influenza A viruses H1N1 and H5N1 in single infection as well as in co-infection. We demonstrated PV's activity against various SARS-CoV-2 variants and identified its action at the post-entry stage of the viral life cycle. Notably, treatment of air-liquid interface (ALI) cultures of primary bronchial epithelial cells with PV significantly inhibited SARS-CoV-2 levels. Additionally, PV was found to attenuate interferon (IFN) signaling independently of viral infection. Mechanistically, PV decreased the activation of the IFN-stimulated response element following stimulation with all three IFN types by suppressing STAT1 and STAT2 phosphorylation and nuclear translocation. Furthermore, the combination of PV with approved COVID-19 therapeutics molnupiravir and remdesivir demonstrated synergistic effects. Given its immunomodulatory effects and clinical availability, PV shows promising potential as a component for combination therapy against COVID-19.
Keywords: SARS‐CoV‐2; antiviral; immunomodulatory; interferon; papaverine.
. 2025 Apr;97(4):e70319.
doi: 10.1002/jmv.70319. Papaverine Targets STAT Signaling: A Dual-Action Therapy Option Against SARS-CoV-2
Philipp Reus 1 2 , Emma Torbica 2 , Tamara Rothenburger 2 , Marco Bechtel 2 , Joshua Kandler 2 , Sandra Ciesek 2 3 , Philip Gribbon 1 , Aimo Kannt 3 , Jindrich Cinatl 2 4 , Denisa Bojkova 2
Affiliations
- PMID: 40171981
- DOI: 10.1002/jmv.70319
Papaverine (PV) has been previously identified as a promising candidate in SARS-CoV-2 repurposing screens. In this study, we further investigated both its antiviral and immunomodulatory properties. PV displayed antiviral efficacy against SARS-CoV-2 and influenza A viruses H1N1 and H5N1 in single infection as well as in co-infection. We demonstrated PV's activity against various SARS-CoV-2 variants and identified its action at the post-entry stage of the viral life cycle. Notably, treatment of air-liquid interface (ALI) cultures of primary bronchial epithelial cells with PV significantly inhibited SARS-CoV-2 levels. Additionally, PV was found to attenuate interferon (IFN) signaling independently of viral infection. Mechanistically, PV decreased the activation of the IFN-stimulated response element following stimulation with all three IFN types by suppressing STAT1 and STAT2 phosphorylation and nuclear translocation. Furthermore, the combination of PV with approved COVID-19 therapeutics molnupiravir and remdesivir demonstrated synergistic effects. Given its immunomodulatory effects and clinical availability, PV shows promising potential as a component for combination therapy against COVID-19.
Keywords: SARS‐CoV‐2; antiviral; immunomodulatory; interferon; papaverine.