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

by Selleckchem | Nov 06 2023

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.

Comments:

It seems like you have provided information about a potential therapeutic approach for the treatment of COVID-19 using a combination of pamapimod and pioglitazone. Based on the information you've given, it appears that these drugs have been found to possess potent and synergistic activity in inhibiting the replication of SARS-CoV-2 in vitro (in cell culture).

Pamapimod is a selective inhibitor of p38 Mitogen-Activated Protein Kinase alpha (p38 MAPKα), which has been identified as a key pathway for SARS-CoV-2 replication. Pioglitazone, on the other hand, is an anti-inflammatory drug approved for the treatment of type 2 diabetes.

The combination of pamapimod and pioglitazone has shown similar antiviral potency across different cell types and has demonstrated activity against various SARS-CoV-2 variants, including the Wuhan type as well as the Alpha, Beta, Gamma, Delta, and Omicron variants. These findings suggest that this drug combination could be effective in reducing the duration and severity of COVID-19 in patients.

It's worth noting that the information you provided indicates that these findings are based on in vitro studies, which means they were conducted in a laboratory setting using cell cultures. While these results are promising, further evaluation is needed to determine the safety and efficacy of this drug combination in clinical settings.

You mentioned that an ongoing phase II clinical study is currently evaluating the assumption that the combination of pamapimod and pioglitazone could be a potential therapy for COVID-19. Clinical studies like these are crucial to assess the effectiveness of treatments in real-world scenarios and provide more definitive evidence.

It's important to keep in mind that my knowledge cutoff is in September 2021, so I may not have the most up-to-date information on the progress of this specific study or any subsequent developments. I would recommend referring to recent scientific literature, trusted health authorities, and official sources for the latest updates on potential therapeutics for COVID-19.