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
the defensive response against invading pathogens. Its tight regulation
is lost during infection by the severe acute respiratory coronavirus 2
(SARS-CoV-2) and thus uncontrolled pyroptosis disrupts the immune system
and the integrity of organs defining the critical conditions in patients
with high viral load. Molecular pathways engaged downstream to the
formation and stabilization of the inflammasome -required to execute the
process- have been uncovered and drugs are available for their
regulation. On the contrary, pharmacological inferring of the upstream
events -which are critical to sense and interpret the initial damage by
the pathogen- is far from being elucidated. This limits our capacity to
identify early markers and targets to ameliorate SARS-CoV-2 linked
pyroptosis. Here we aim to raise attention on mitochondria and pathways
leading to its dysfunction with the goal to inform early steps of
inflammasome and devise tools to interpret and counteract diseases by
the SARS-CoV-2.