Fig. 2.

The mechanism of infection and replication (life-cycle) of SARS-CoV-2 and other coronaviruses in host cells. (1) The viral entry into host cell on binding to host cell ACE2 receptor followed by membrane fusion or endocytosis and deposition of viral genomic RNA (g-RNA) into host cell cytoplasm. (2) The virus replicase genes ORF1a and ORF1b from (+)-sense- g-RNA are translated by host translation machinery into functional polyproteins pp1a and pp1ab, respectively. (3) The polyproteins 1a and 1 ​ab are cotranslationally cleaved by two virus cysteine proteases, papain-like protease (PLpro) and 3-chymotrypsin-like protease (3CLpro) or main protease (Mpro) into 16 non-structural proteins (nsp1-16) and to form viral replicase-transcriptase complex (RTC) or RdRp complex. (4) The RTC uses the viral g-RNA as a template to generate (−)-sense subgenomic (sg) and genome-length (g) RNAs. (5) These (−)-sense sg- and g-RNAs are used as templates for synthesis of (+)- sense full-length progeny genomes and sg- RNAs. (6) The components of RTC carry out transcription and replication of virus in CMs adjacent to DMVs that are both derived from host cell rough endoplasmic reticulum (ER). (7) The (+)-sense g-RNA is bound by viral nucleocapsid (N) protein and buds into ERGIC and these nucleocapsid buds are decorated with structural proteins S, E, and M translated from (+)-sense sg-RNAs to form enveloped virions. (8) and (9) The newly formed enveloped virions are exported from the infecred cell into adjacent host cell by exocytosis for infection and replication. [Adapted from Ref. [24]].