Taming the Autophagy as a Strategy for Treating COVID-19

Abstract

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.

Cyclovirobuxine D Induced-Mitophagy through the p65/BNIP3/LC3 Axis Potentiates Its Apoptosis-Inducing Effects in Lung Cancer Cells

“…Based on its autophagy/mitophagy induction activity, its potential application in the treatment of other diseases also deserves to be explored. Under certain conditions, the activation of autophagy may serve as a treatment strategy to defend against intracellular bacteria, parasites and virus infection by targeting intracellular microorganisms (xenophagy) and mediating the clearance of microorganisms or via modulating the antiviral immune response of organisms to defend against infection [ 44 ]. In terms of anti-infection, whether CVB-D possesses potential applications is largely unknown and deserves to be explored.…”

C9orf72 Intermediate Repeats Confer Genetic Risk for Severe COVID-19 Pneumonia Independently of Age

“…Of note, autophagy dysfunctions are often associated with inflammatory and autoimmune diseases [44] and innate immune responses and inflammation, crucial in anti-viral responses, are regulated by autophagy [54]. Several studies have shown that many viruses, like coronaviruses, have evolved strategies to evade the host response by directly hijacking the autophagy pathway in support of their life cycle and spread or by disrupting the host control on the production of anti-viral cytokines [54][55][56]. Host genetics also contributes to aberrant immunity in autoimmune diseases and susceptibility to infectious diseases in humans and such variants are often found in genes involved in the immune response and inflammation [44,45].…”

Autophagy, Unfolded Protein Response, and Neuropilin-1 Cross-Talk in SARS-CoV-2 Infection: What Can Be Learned from Other Coronaviruses

“…Melatonin reduces oxidative stress, reinforces UPR, and unlocks the autophagy blockage caused by the virus, allowing autophagosome maturation and a decrease in double-membrane vesicle formation and viral replication capacity [ 55 ]. Moreover, photothermal therapy could enhance ROS production, which is shown to downregulate the Akt-mTOR-p70S6K pathway, resulting in autophagy [ 153 ].…”