Fig. 1

Replication cycle and infection process of SARS-CoV-2

Virus entry into host cells is the first step of severe acute respiratory syndrome CoV 2 (SARS-CoV-2) infection. The entry of SARS-CoV-2 is mediated by the combination of S protein with the host cell surface receptor angiotensin-converting enzyme 2 (ACE2) with the aid of the enzyme transmembrane protease serine 2 (TMPRSS2). Subsequently, the virus entering host cells fuses with the lysosomal membrane, and the viral nucleocapsid is uncoated to be exposed in the cytoplasm, which marks the beginning of virus replication. The positive-sense genome RNA, which serves as the first mRNA of infection, replicates into complete virions processed through the host cell nuclear, ER, and ER–Golgi intermediate complex (ERGIC). Full-length genomic RNA (gRNA), also known as the positive-sense genome, is replicated as the template for the synthesis of progeny genomes and a nested set of subgenomic RNA (sgRNA) via a negative-sense intermediate using RNA polymerase (RdRP). The gRNA can be translated into the polyproteins pp1a and pp1ab, which are cleaved to form individual replicate complex NSP. sgRNAs encode viral structural and accessory proteins, among which the membrane-bound structural proteins M, S, and E are inserted into the ER and then into the ERGIC. Finally, mature progeny virions in smooth-walled vesicles are transported to the plasma membrane and released by exocytosis to perform their function

Abbreviations: ACE2: angiotensin-converting enzyme 2; E: envelope; ER: endoplasmic reticulum; ERGIC: ER–Golgi intermediate complex; gRNA: genomic RNA; M: membrane; NSP: nonstructural proteins; RdRP: RNA-dependent RNA polymerase; S: spike glycoprotein; SARS-CoV-2: severe acute respiratory syndrome CoV 2; sgRNA: subgenomic RNA; TMPRSS2: transmembrane protease serine 2