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  Indian J Med Microbiol
 

Figure 1: Schematic illustration of the molecular pathways for SARS-CoV-2-induced autophagy dysregulation. SARS-CoV-2-derived open-reading frame (ORF) protein 3a (ORF3a) can inhibit mitochondrial fusion by binding to host protein mitofusin (Mfn) 1 and 2. ORF3a can also inhibit autophagosome-lysosome (A-L) fusion by binding to the host protein Vamp6 (VPS39) and HOPS complex. Two other SARS-CoV-2-derived proteins, ORF8 and nucleocapsid protein (NCP) both can bind to La ribonucleoprotein 1, translational regulator (LARP1), and FKBP prolyl isomerase 7 (FKBP7) and inhibit mammalian target of rapamycin complex 1 (mTORC1), thereby activate autophagy. Papain-like protease can inhibit autophagy by binding to the Unc-51 like autophagy activating kinase (ULK1) and autophagy-related 13 protein (ATG13) complex. SARS-CoV-2-mediated autophagy dysfunction can elicit a massive cytokine storm leading to the death of vulnerable cells like neurons and microglia. Purple boxes denote SARS-CoV-2-derived proteins, while black boxes denote host proteins.

<b>Figure 1: Schematic illustration of the molecular pathways for SARS-CoV-2-induced autophagy dysregulation.</b>
SARS-CoV-2-derived open-reading frame (ORF) protein 3a (ORF3a) can inhibit mitochondrial fusion by binding to host protein mitofusin (Mfn) 1 and 2. ORF3a can also inhibit autophagosome-lysosome (A-L) fusion by binding to the host protein Vamp6 (VPS39) and HOPS complex. Two other SARS-CoV-2-derived proteins, ORF8 and nucleocapsid protein (NCP) both can bind to La ribonucleoprotein 1, translational regulator (LARP1), and FKBP prolyl isomerase 7 (FKBP7) and inhibit mammalian target of rapamycin complex 1 (mTORC1), thereby activate autophagy. Papain-like protease can inhibit autophagy by binding to the Unc-51 like autophagy activating kinase (ULK1) and autophagy-related 13 protein (ATG13) complex. SARS-CoV-2-mediated autophagy dysfunction can elicit a massive cytokine storm leading to the death of vulnerable cells like neurons and microglia. Purple boxes denote SARS-CoV-2-derived proteins, while black boxes denote host proteins.