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Article

Synergistic Antiviral Activity of Pamapimod and Pioglitazone against SARS-CoV-2 and Its Variants of Concern

1
Institute of Virology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
2
Kinarus Therapeutics AG, 4057 Basel, Switzerland
*
Authors to whom correspondence should be addressed.
Academic Editor: Giovanni Maga
Int. J. Mol. Sci. 2022, 23(12), 6830; https://doi.org/10.3390/ijms23126830
Received: 5 May 2022 / Revised: 8 June 2022 / Accepted: 10 June 2022 / Published: 20 June 2022
(This article belongs to the Special Issue Antivirals and Vaccines)
The SARS-CoV-2 pandemic remains a major public health threat, especially due to newly emerging SARS-CoV-2 Variants of Concern (VoCs), which are more efficiently transmitted, more virulent, and more able to escape naturally acquired and vaccine-induced immunity. Recently, the protease inhibitor Paxlovid® and the polymerase inhibitor molnupiravir, both targeting mutant-prone viral components, were approved for high-risk COVID-19 patients. Nevertheless, effective therapeutics to treat COVID-19 are urgently needed, especially small molecules acting independently of VoCs and targeting genetically stable cellular pathways which are crucial for viral replication. Pamapimod is a selective inhibitor of p38 Mitogen-Activated Protein Kinase alpha (p38 MAPKα) that has been extensively clinically evaluated for the treatment of rheumatoid arthritis. Signaling via p38 has recently been described as a key pathway for the replication of SARS-CoV-2. Here, we reveal that the combination of pamapimod with pioglitazone, an anti-inflammatory and approved drug for the treatment of type 2 diabetes, possesses potent and synergistic activity to inhibit SARS-CoV-2 replication in vitro. Both drugs showed similar antiviral potency across several cultured cell types and similar antiviral activity against SARS-CoV-2 Wuhan type, and the VoCs Alpha, Beta, Gamma, Delta, and Omicron. These data support the combination of pamapimod and pioglitazone as a potential therapy to reduce duration and severity of disease in COVID-19 patients, an assumption currently evaluated in an ongoing phase II clinical study. View Full-Text
Keywords: COVID-19; SARS-CoV-2; coronavirus; variants of concern; virus variants; pioglitazone; pamapimod; p38-inhibitor; PPRy-agonist; cellular targets COVID-19; SARS-CoV-2; coronavirus; variants of concern; virus variants; pioglitazone; pamapimod; p38-inhibitor; PPRy-agonist; cellular targets
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MDPI and ACS Style

Setz, C.; Große, M.; Auth, J.; Fröba, M.; Rauch, P.; Bausch, A.; Wright, M.; Schubert, U. Synergistic Antiviral Activity of Pamapimod and Pioglitazone against SARS-CoV-2 and Its Variants of Concern. Int. J. Mol. Sci. 2022, 23, 6830. https://doi.org/10.3390/ijms23126830

AMA Style

Setz C, Große M, Auth J, Fröba M, Rauch P, Bausch A, Wright M, Schubert U. Synergistic Antiviral Activity of Pamapimod and Pioglitazone against SARS-CoV-2 and Its Variants of Concern. International Journal of Molecular Sciences. 2022; 23(12):6830. https://doi.org/10.3390/ijms23126830

Chicago/Turabian Style

Setz, Christian, Maximilian Große, Janina Auth, Maria Fröba, Pia Rauch, Alexander Bausch, Matthew Wright, and Ulrich Schubert. 2022. "Synergistic Antiviral Activity of Pamapimod and Pioglitazone against SARS-CoV-2 and Its Variants of Concern" International Journal of Molecular Sciences 23, no. 12: 6830. https://doi.org/10.3390/ijms23126830

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