Dr. Grimes authors paper on p38 MAPK pathway in COVID-19

Dr. Grimes authors paper on p38 MAPK pathway in COVID-19

Posted on July 31st, 2020

SPARK co-director Dr. Kevin Grimes along with Dr. Joseph Grimes published a paper in the Journal of Molecular and Cellular Cardiology in May examining the p38 MAPK pathway and its role in COVID-19 pathology.

In the paper, the authors discuss the p38 mitogen-activated protein kinase (MAPK) enzyme and its connection to Angiotensin-converting enzyme 2 (ACE2), through which SARS-CoV-2 enters cells.

The authors suggest therapeutic inhibition of p38 could attenuate COVID-19 infection.

“The p38 MAPK pathway is a key mediator of inflammation implicated in lung and heart injury” and “plays a crucial role in the release of pro-inflammatory cytokines such as IL-6,” the authors wrote. “ACE2 converts Angiotensin II (Ang II) into Angiotensin 1–7 (Ang 1–7),” mediated through p38 MAPK activation. “The loss of ACE2 activity upon viral entry may therefore allow Ang II mediated activation of p38 to predominate in the lungs and heart as Ang 1–7 is downregulated.”

In addition, “SARS-CoV was previously shown to directly upregulate p38 activity via a viral protein,” and SARS-CoV-2 may employ a similar mechanism.

Overactivation of p38 MAPK activity can also explain inflammation, thrombosis, and vasoconstriction in COVID-19 patients.

The authors conclude that “safe and well tolerated p38 MAPK inhibitors that are already in clinical development could be readily repurposed in randomized, controlled trials enrolling patients at risk for serious COVID-19 complications.”

Dr. Kevin Grimes and colleagues at SPARK are now gearing up to begin clinical trials of compounds to treat COVID-10 along this pathway.