Coronavirus replication cycle. Coronavirus infection begins with the attachment of the S1 domain of the spike protein (S) with its cognate receptor. This drives the conformational change in the S2 subunit in S, promoting the fusion of the viral and cell plasma membrane. Following the release of the nucleocapsid to the cytoplasm, the viral gRNA is translated through ribosomal frameshifting to produce polyproteins pp1a and pp1ab. pp1a and pp1ab are autoproteolytically processed by host and viral proteases to generate 16 non-structural proteins (NSPs), which will then be assembled to form the replicase-polymerase. The replicase-polymerase is involved in the coronaviral replication, a process in which the genomic RNA are replicated and the subgenomic RNA will be transcribed and translated to form the structural proteins. The viral products produced will be assembled in the ERGIC, and bud out as a smooth-wall vesicle to the plasma membrane to egress via exocytosis. Host factors that promote infection and inhibit infection are highlighted in green and red, respectively. APN, aminopeptidase N; ACE2, Angiotensin converting enzyme 2; DPP4, dipeptidyl peptidase 4; 9-O-Ac Sialic Acid, 9-O-Acetylated Sialic Acid; IFITM, Interferon induced transmembrane protein; ATP1A1, ATPase, Na+/K+ Transporting, Alpha 1 Polypeptide; HnRNP A1, Heterogeneous nuclear ribonucleoprotein A1; MADP1, Zinc Finger CCHC-Type and RNA Binding Motif 1; DDX1, ATP-dependent RNA Helicase; PCBP1/2, Poly r(C) binding protein 1/2; PABP, Poly A binding protein; COPB2, Coatomer protein complex, subunit beta 2 (beta prime); GAPDH, Glyceraldehyde 3-phosphate dehydrogenase; ERGIC, Endoplasmic reticulum Golgi intermediate compartment; ER, endoplasmic reticulum; VCP, Valosin-Containing Protein.