Figure 2.

Possible involvement of SARS-CoV-2 ORF3a during viral life cycle. SARS-CoV-2 viral life cycle starts with the attachment of a virion to a host cell surface receptor ACE2 via S protein (A). A conformational change in S induces virus membrane fusion with either the host plasma membrane or the endosome membrane, leading to the release of viral RNA into the cytoplasm (B). ORF3a localizes on plasma membrane where it forms Ca²⁺ ion channel or it may interact with S protein to promote virus uptake. It also associates with early, late endosomes and lysosomes to facilitate endocytosis (C). Upon viral entry, genomic +ssRNA is uncoated to allow direct translation of polyproteins, transcription of sgRNAs, and replication of the viral genome through RTC on DMVs, where ORF3a may exert its effect (C). Newly produced envelope proteins are inserted into the rough ER membranes. Nucleocapsid proteins bind to genomic +ssRNA to form nucleocapsids. After budding into the ER–Golgi intermediate compartment (ERGIC), the virions are matured in smooth-walled vesicles and subsequently released from infected cell via exocytosis (D). ORF3a promotes viral release through lysosomal exocytosis pathway. This figure is generated using Adobe Illustrator 2020.