Autophagy in Inflammatory Response against SARS-CoV-2

Abstract

The coronavirus disease pandemic, which profoundly reshaped the world in 2019 (COVID-19), and is currently ongoing, has affected over 200 countries, caused over 500 million cumulative cases, and claimed the lives of over 6.4 million people worldwide as of August 2022. The causative agent is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Depicting this virus’ life cycle and pathogenic mechanisms, as well as the cellular host factors and pathways involved during infection, has great relevance for the development of therapeutic strategies. Autophagy is a catabolic process that sequesters damaged cell organelles, proteins, and external invading microbes, and delivers them to the lysosomes for degradation. Autophagy would be involved in the entry, endo, and release, as well as the transcription and translation, of the viral particles in the host cell. Secretory autophagy would also be involved in developing the thrombotic immune-inflammatory syndrome seen in a significant number of COVID-19 patients that can lead to severe illness and even death. This review aims to review the main aspects that characterize the complex and not yet fully elucidated relationship between SARS-CoV-2 infection and autophagy. It briefly describes the key concepts regarding autophagy and mentions its pro- and antiviral roles, while also noting the reciprocal effect of viral infection in autophagic pathways and their clinical aspects.

STING agonists as promising vaccine adjuvants to boost immunogenicity against SARS-related coronavirus derived infection: possible role of autophagy

“…Noticeably, a prominent role of autophagy in the inflammatory response (especially thrombotic immune-inflammatory syndrome) follows SARS-CoV-2 infection [ 65 ]. Autophagy induction could impede the consecutive robust inflammatory response triggered by SARS-CoV-2 infection, leading to a multi-organ failure [ 65 ].…”

“…Noticeably, a prominent role of autophagy in the inflammatory response (especially thrombotic immune-inflammatory syndrome) follows SARS-CoV-2 infection [ 65 ]. Autophagy induction could impede the consecutive robust inflammatory response triggered by SARS-CoV-2 infection, leading to a multi-organ failure [ 65 ]. Calling attention, cells exposed to the SARS-CoV-2 infection can escape immune response mediated by IFN-I induction (markedly increase of green fluorescent protein (GFP)-LC3 positive autophagosomes) in vitro [ 66 ].…”

Insights into COVID-19: Perspectives on Drug Remedies and Host Cell Responses

“…An excessive inflammatory response to SARS-CoV-2 is thought to be a major cause of disease severity and death in patients with COVID-19 [37]. This is associated with high levels of circulating cytokines and substantial mononuclear cell infiltration in the lungs, heart, kidneys, and other organs [38][39][40].…”

What Long COVID Prevention Strategies Suggest About Its Pathophysiology

“…Metformin may also abrogate SARS-CoV-2 nonstructural protein 6–mediated lysosomal deacidification, thereby restoring autophage flux [ 17 ]. Restoration of autophage flux, in turn, may reduce consequent inflammation [ 17 ], facilitate viral clearance, and reduce the effectiveness of viral replication [ 18 ].…”