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

Setz C, Große M, Auth J, Froba M, Rauch P, Bausch A, Wright M, Schubert U (2022)

Publication Type: Journal article

Publication year: 2022

Journal

International Journal of Molecular Sciences MDPI

Book Volume: 23

Journal Issue: 12

DOI: 10.3390/ijms23126830

Abstract

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 (R) 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 MAPK alpha) 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.

Authors with CRIS profile

Christian Setz Institute of Clinical and Molecular Virology Maximilian Große Institute of Clinical and Molecular Virology Janina Auth Professur für Virologie Ulrich Schubert Professur für Virologie

Involved external institutions

Kinarus AG CH Switzerland (CH)

How to cite

APA:

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

MLA:

Setz, Christian, et al. "Synergistic Antiviral Activity of Pamapimod and Pioglitazone against SARS-CoV-2 and Its Variants of Concern." International Journal of Molecular Sciences 23.12 (2022).

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