SARS-CoV-2 infectivity is effectively treated and prevented using a combination of MEK and p38 inhibitors

The recent emergence of the new pathogen SARS-CoV-2 (COVID19) virus in China and its rapid pandemic spread, posed an unprecedented health emergency that demanded an urgent response. In the absence of specific treatments, the current therapeutic arsenal offers a plethora of drugs, approved for other uses, amenable for repurposing against COVID-19, based on their mechanisms of action. Previous findings have demonstrated that the signaling pathways mediated by ERK and p38 Mitogen-Activated Protein Kinases (MAPK) are involved in COVID-19 multiplication at different stages. As such, inhibitors targeting these pathways block COVID-19 replication. Moreover, p38 inhibitors have also proven effective against the inflammatory response elicited by COVID-19 infection. The MEK inhibitors (MEKi) Trametinib/Selumetinib/Cobimetinib are FDA/EMA-approved drugs for metastatic melanoma treatment; whereas the p38 inhibitor Losmapimod is currently in phase II trials for chronic obstructive pulmonary disease. Herein, we show a drug class-effect MEK and p38 inhibitors in suppressing SARS-CoV-2- virus infection of human cells. We aim at establishing these MAPK inhibitors' potential as antivirals in comparison to the most effective therapeutics currently utilized in the clinic against COVID-19, namely: Hydroxychloroquine, the antiretroviral Remdesivir, and the IL6 inhibitor Tocilizumab.