PMC:7067204 / 10264-13197 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7067204","sourcedb":"PMC","sourceid":"7067204","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7067204","text":"There are 12 putative, functional open reading frames (orfs) expressed from a nested set of 9 subgenomic mRNAs carrying a conserved leader sequence in the genome, 9 transcription-regulatory sequences, and 2 terminal untranslated regions. The 5′- and 3′-UTRs are 265 and 358 nucleotides long, respectively. The 5′- and 3 ′-UTR sequences of 2019-nCoV are similar to those of other βCoVs with nucleotide identities of ⩾83.6%. The large replicase polyproteins pp1a and pp1ab encoded by the partially overlapping 5′-terminal orf1a/b within the 5′ two-thirds of the genome is proteolytic cleaved into 16 putative non-structural proteins (nsps). These putative nsps included two viral cysteine proteases, namely, nsp3 (papain-like protease) and nsp5 (chymotrypsin-like, 3C-like, or main protease), nsp12 (RNA-dependent RNA polymerase [RdRp]), nsp13 (helicase), and other nsps which are likely involved in the transcription and replication of the virus (Table 2). There are no remarkable differences between the orfs and nsps of 2019-nCoV with those of SARS-CoV (Table 3). The major distinction between SARSr-CoV and SARS-CoV is in orf3b, Spike and orf8 but especially variable in Spike S1 and orf8 which were previously shown to be recombination hot spots.\nTable 2. Putative functions and proteolytic cleavage sites of 16 nonstructural proteins in orf1a/b as predicted by bioinformatics.\nNSP Putative function/domain Amino acid position Putative cleave site\nnsp1 suppress antiviral host response M1 – G180 (LNGG'AYTR)\nnsp2 unknown A181 – G818 (LKGG'APTK)\nnsp3 putative PL-pro domain A819 – G2763 (LKGG'KIVN)\nnsp4 complex with nsp3 and 6: DMV formation K2764 – Q3263 (AVLQ'SGFR)\nnsp5 3CL-pro domain S3264 – Q3569 (VTFQ'SAVK)\nnsp6 complex with nsp3 and 4: DMV formation S3570 – Q3859 (ATVQ'SKMS)\nnsp7 complex with nsp8: primase S3860 – Q3942 (ATLQ'AIAS)\nnsp8 complex with nsp7: primase A3943 – Q4140 (VKLQ'NNEL)\nnsp9 RNA/DNA binding activity N4141 – Q4253 (VRLQ'AGNA)\nnsp10 complex with nsp14: replication fidelity A4254 – Q4392 (PMLQ'SADA)\nnsp11 short peptide at the end of orf1a S4393 – V4405 (end of orf1a)\nnsp12 RNA-dependent RNA polymerase S4393 – Q5324 (TVLQ'AVGA)\nnsp13 helicase A5325 – Q5925 (ATLQ'AENV)\nnsp14 ExoN: 3′–5′ exonuclease A5926 – Q6452 (TRLQ'SLEN)\nnsp15 XendoU: poly(U)-specific endoribonuclease S6453 – Q6798 (PKLQ'SSQA)\nnsp16 2'-O-MT: 2'-O-ribose methyltransferase S6799 – N7096 (end of orf1b)\nTable 3. Amino acid identity between the 2019 novel coronavirus and bat SARS-like coronavirus or human SARS-CoV.\nAmino acid identity (%) 2019-nCoV 2019-nCoV\n  vs. bat-SL-CoVZXC21 vs. SARS-CoV\nNSP1 96 84\nNSP2 96 68\nNSP3 93 76\nNSP4 96 80\nNSP5 99 96\nNSP6 98 88\nNSP7 99 99\nNSP8 96 97\nNSP9 96 97\nNSP10 98 97\nNSP11 85 85\nNSP12 96 96\nNSP13 99 100\nNSP14 95 95\nNSP15 88 89\nNSP16 98 93\nSpike 80 76\nOrf3a 92 72\nOrf3b 32 32\nEnvelope 100 95\nMembrane 99 91\nOrf6 94 69\nOrf7a 89 85\nOrf7b 93 81\nOrf8/Orf8b 94 40\nNucleoprotein 94 94\nOrf9b 73 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