Meta-Biol

• Pathways

After synthesizing the complementary minus RNA of the plus strand viral genomic RNA, virally encoded RNA-dependent RNA polymerase (nsp12, also known as RdRP) uses the minus strand as a template to generate viral genomic RNA that can be packaged into virions. Purified SARS-CoV-1 nsp12 shows both primer dependent and primer-independent RNA synthesis activity in vitro. nsp12 is able to initiate RNA synthesis with as little as 37 nucleotides of RNA from the 3’ end of the minus strand viral RNA (complementary to the 5’-UTR of the plus strand genomic RNA - c5’-UTR). Similar to the 3'-UTR of the plus strand, the 3' end of the minus strand (c5’-UTR) is predicted to form a stable stem-loop structure and seems to be the minimal cis-acting RNA element required for nsp12 to initiate RNA synthesis using the minus strand as a template (Ahn et al. 2012). It is unclear if replication of the minus strand is primer-dependent. The complex of nsp7 and nsp8 confers processivity to nsp12 (Subissi et al. 2014).