Taming the Autophagy as a Strategy for Treating COVID-19

García-Pérez, Blanca Estela; González-Rojas, Juan Antonio; Salazar, Ma Isabel; Torres-Torres, Carlos; Castrejón-Jiménez, Nayeli Shantal

Currently, an efficient treatment for COVID-19 is still unavailable, and people are continuing to die from complications associated with SARS-CoV-2 infection. Thus, the development of new therapeutic approaches is urgently needed, and one alternative is to target the mechanisms of autophagy. Due to its multifaceted role in physiological processes, many questions remain unanswered about the possible advantages of inhibiting or activating autophagy. Based on a search of the literature in this field, a novel analysis has been made to highlight the relation between the mechanisms of autophagy in antiviral and inflammatory activity in contrast with those of the pathogenesis of COVID-19. The present analysis reveals a remarkable coincidence between the uncontrolled inflammation triggered by SARS-CoV-2 and autophagy defects. Particularly, there is conclusive evidence about the substantial contribution of two concomitant factors to the development of severe COVID-19: a delayed or absent type I and III interferon (IFN-I and IFN-III) response together with robust cytokine and chemokine production. In addition, a negative interplay exists between autophagy and an IFN-I response. According to previous studies, the clinical decision to inhibit or activate autophagy should depend on the underlying context of the pathological timeline of COVID-19. Several treatment options are herein discussed as a guide for future research on this topic.