Using the genomic RNA as a template, the coronavirus replicase synthesizes full-length negative-sense antigenome, which in turn serves as a template for the synthesis of new genomic RNA (Masters 2006). The polymerase can also switch template during discontinuous transcription of the genome at specific sites called transcription-regulated sequences, thereby producing a 5'-nested set of negative-sense sgRNAs, which are used as templates for the synthesis of a 3'-nested set of positive-sense sgRNAs (Masters 2006). Although genome replication/transcription is mainly mediated by the viral replicase and confines in the replication-transcription complex (RTC), the involvement of various additional viral and host factors has been implicated. For instance, coronavirus N protein is known to serve as an RNA chaperone and facilitate template switching (Zúñiga et al. 2007, Zúñiga et al. 2010). Importantly, the N protein of SARS-CoV-1 and mouse hepatitis virus (MHV-JHM) is also phosphorylated by the host glycogen synthase kinase 3 (GSK3), and inhibition of GSK3 was shown to inhibit viral replication in Vero E6 cells infected with SARS-CoV-1 (Wu et al. 2009). Additionally, GSK3-mediated phosphorylation of the MHV-JHM N protein recruited an RNA-binding protein DEAD-box helicase 1 (DDX1), which facilitates template read-through, favoring the synthesis of genomic RNA and longer sgRNAs (Wu et al. 2014). Another RNA-binding protein called heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) can also bind tightly to SARS-CoV N protein and potentially regulate viral RNA synthesis (Luo et al. 2005). Host RNA-binding proteins could also bind directly to untranslated regions (UTRs) of the coronavirus genome to modulate replication/transcription, such as zinc finger CCHC-type and RNA-binding motif 1 (ZCRB1) binding to the 5-UTR of IBV (Tan et al. 2012), mitochondrial aconitase binding to the 3' UTR of MHV (Nanda and Leibowitz 2001), and poly(A)-binding protein (PABP) to the poly(A) tail of bovine coronavirus (Spagnolo and Hogue 2000). For review, please refer to Snijder et al. 2016 and Fung and Liu 2019.