Pyroptosis targeting via mitochondria: an educated guess to fast-track COVID-19 therapies

Abstract

Pyroptosis, is a specialized form of inflammatory cell death which aids\nthe defensive response against invading pathogens. Its tight regulation\nis lost during infection by the severe acute respiratory coronavirus 2\n(SARS-CoV-2) and thus uncontrolled pyroptosis disrupts the immune system\nand the integrity of organs defining the critical conditions in patients\nwith high viral load. Molecular pathways engaged downstream to the\nformation and stabilization of the inflammasome -required to execute the\nprocess- have been uncovered and drugs are available for their\nregulation. On the contrary, pharmacological inferring of the upstream\nevents -which are critical to sense and interpret the initial damage by\nthe pathogen- is far from being elucidated. This limits our capacity to\nidentify early markers and targets to ameliorate SARS-CoV-2 linked\npyroptosis. Here we aim to raise attention on mitochondria and pathways\nleading to its dysfunction with the goal to inform early steps of\ninflammasome and devise tools to interpret and counteract diseases by\nthe SARS-CoV-2.