The role of SARS-CoV-2 ORF7a in autophagy flux disruption: implications for viral infection and pathogenesis

Although alterations in the autophagy-lysosome pathway have been observed in the SARS-CoV-2 infection and invasion process since the outbreak of the coronavirus disease in 2019, the in-depth mechanism of autophagic and lysosomal reprogramming by SARS-CoV-2 has yet to be well identified. Our recent study unveiled a pivotal role played by the open reading frame 7a (ORF7a) protein in the SARS-CoV-2 genome, particularly in the modulation of macroautophagy/autophagy flux and function during viral infection and pathogenesis. Our study elucidated the underlying molecular mechanisms by which SARS-CoV-2 ORF7a intercepts autophagic flux, evades host autophagy-lysosome degradation, and accelerates viral infection and progeny germination. Furthermore, our study highlights that ORF7a can be a therapeutic target, and glecaprevir may hold potential as a drug against SARS-CoV-2 by targeting ORF7a. The key observations revealed in this study also contribute to a growing understanding of the function of SARS-CoV-2 ORF7a and the mechanisms underlying COVID-2019 treatment.