Early SARS-CoV-2 Infection Events

The initial steps of SARS-CoV-2 infection involve the specific binding of the coronavirus spike (S) protein to the cellular entry receptor, angiotensin-converting enzyme 2 (ACE2). The expression and tissue distribution of entry receptors consequently influence viral tropism and pathogenicity. Besides receptor binding, the proteolytic cleavage of coronavirus S proteins by host cell-derived proteases is essential to permit fusion. SARS-CoV has been shown to use the cell-surface serine protease TMPRSS2 for priming and entry, although the endosomal cysteine proteases cathepsin B (CatB) and CatL can also assist in this process. During the intracellular life cycle SARS-CoV-2 express and replicate their genomic RNA to produce full-length copies that are incorporated into newly produced viral particles. Coronaviruses possess remarkably large RNA genomes flanked by 5' and 3' untranslated regions that contain cis-acting secondary RNA structures essential for RNA synthesis. At the 5' end, the genomic RNA features two large open reading frames (ORFs; ORF1a and ORF1b) that occupy two-thirds of the capped and polyadenylated genome. Coronavirus S proteins are homotrimeric class I fusion glycoproteins that are divided into two functionally distinct parts (S1 and S2). The surface-exposed S1 contains the receptor-binding domain (RBD) that specifically engages the host cell receptor, thereby determining virus cell tropism and pathogenicity. Besides receptor binding, the proteolytic cleavage of coronavirus S proteins by host cell-derived proteases is essential to permit fusion. SARS-CoV has been shown to use the cell-surface serine protease TMPRSS2 for priming and entry, although the endosomal cysteine proteases cathepsin B (CatB) and CatL can also assist in this process The release of the coronavirus genome into the host cell cytoplasm upon entry marks the onset of a complex programme of viral gene expression, which is highly regulated in space and time. The translation of ORF1a and ORF1b from the genomic RNA produces two polyproteins, pp1a and pp1ab, respectively. ORF1a and ORF1b encode 15-16 non-structural proteins (nsp), of which 15 compose the viral replication and transcription complex (RTC) that includes, amongst others, RNA-processing and RNA-modifying enzymes and an RNA proofreading function necessary for maintaining the integrity of the >30kb coronavirus genome. The establishment of the viral RTC is crucial for virus replication The release of the coronavirus genome into the host cell cytoplasm upon entry marks the onset of a complex programme of viral gene expression, here divided into early and late.

Summary from Reactome (R-HSA-9772572), read 2026-09-23.