Genetic relatedness of the novel human group C betacoronavirus to Tylonycteris bat coronavirus HKU4 and Pipistrellus bat coronavirus HKU5

Woo, Patrick CY; Lau, Susanna KP; Li, Kenneth SM; Tsang, Alan KL; Yuen, Kwok-Yung

HCoV-EMC has the same basic genome structure as Ty-BatCoV HKU4 and Pi-BatCoV HKU5 (Figure 1 ). It also possesses the same putative transcription regulatory sequence (TRS) motif, 5'-ACGAAC-3', as Ty-BatCoV HKU4 and Pi-BatCoV HKU5, at the 3' end of the leader sequence and precedes each ORF except NS3c, NS3e and N. This TRS has also been shown to be the TRS for other group B, C and D betaCoVs. The TRS for N is 5'-ACGAAU-3'. Similar to other group B, C and D betaCoVs, the genome of HCoV-EMC has a putative PL pro , which is homologous to PL2 pro of alphaCoVs and group A betaCoVs and PL pro of gammaCoVs and deltaCoVs. Similar to Ty-BatCoV HKU4 and Pi-BatCoV HKU5, no proteolytic cleavage site is present in S of HCoV-EMC. All cysteine residues in S of HCoV-EMC, Ty-BatCoV HKU4 and Pi-BatCoV HKU5 are conserved. In contrast to the genomes of Ty-BatCoV HKU4 and Pi-BatCoV HKU5 which contain four ORFs that encode putative non-structural proteins (NS3a, NS3b, NS3c and NS3d) between S and E, this region of HCoV-EMC contains five ORFs that encode putative nonstructural proteins NS3a, NS3b, NS3c, NS3d and NS3e (Figure 1 ). This is the region of HCoV-EMC that possesses the lowest amino acid identities to those in Ty-BatCoV HKU4 and Pi-BatCoV HKU5. NS3a, NS3b and NS3c of HCoV-EMC possess 42%-43%, 41%-47% and 31% amino acid identities to NS3a, NS3b and NS3c of Ty-BatCoV HKU4 and Pi-BatCoV HKU5, respectively. NS3d of HCoV-EMC is homologous to amino acids 1 to 110/ Abbreviations: a PL pro , papain-like protease ; 3CL pro , chymotrypsin-like protease; RdRp, RNA-dependent RNA polymerase; Hel, helicase; ExoN, 3'-to-5' exonuclease; XendoU, poly(U)-specific endoribonuclease; 2'-O-MT, S-adenosylmethionine-dependent 2'-O-ribose methyltransferase.