Abstract
Coronavirus infection causes endoplasmic reticulum stress inside the cells, which inhibits protein folding. Prolonged endoplasmic reticulum stress causes an apoptotic process of unfolded protein response-induced cell death. Endoplasmic reticulum stress rapidly induces the activation of mTORC1, responsible for the induction of the IRE1-JNK pathway. IRE1-JNK stands out for its dual nature: pro-apoptotic in the first stage of infection, anti-apoptotic in persistently infected cells. Once penetrated the cells, the virus can deflect the mitochondrial function by implementing both waterfalls pro-apoptotic and anti-apoptotic response. The virus prevents, through Open Reading Frame 9b (ORF-9b) interacting with mitochondria, the response of the type I interferon of the cells affected by the infection and is fundamental for generating an antiviral cellular state. ORF-9b has effects on mitochondrial dynamics, inducing fusion and autophagy and promoting cell survival. The recognition of ORF-9b has made it possible to identify it as a molecular target of some existing potentially effective drugs (Midostaurin and Ruxolitinib). Other drugs, with the same target, are currently being tested. Given the great importance of mitochondria in virus-host interaction, in-depth knowledge of the actors and pathways involved is essential to continue developing new therapeutic strategies against SARS CoV2.