PMC:7067204 / 13199-16947 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":"Spike\nSpike glycoprotein comprised of S1 and S2 subunits. The S1 subunit contains a signal peptide, followed by an N-terminal domain (NTD) and receptor-binding domain (RBD), while the S2 subunit contains conserved fusion peptide (FP), heptad repeat (HR) 1 and 2, transmembrane domain (TM), and cytoplasmic domain (CP). We found that the S2 subunit of 2019-nCoV is highly conserved and shares 99% identity with those of the two bat SARS-like CoVs (SL-CoV ZXC21 and ZC45) and human SARS-CoV (Figure 2). Thus the broad spectrum antiviral peptides against S2 would be an important preventive and treatment modality for testing in animal models before clinical trials [18]. Though the S1 subunit of 2019-nCoV shares around 70% identity to that of the two bat SARS-like CoVs and human SARS-CoV (Figure 3(A)), the core domain of RBD (excluding the external subdomain) are highly conserved (Figure 3(B)). Most of the amino acid differences of RBD are located in the external subdomain, which is responsible for the direct interaction with the host receptor. Further investigation of this soluble variable external subdomain region will reveal its receptor usage, interspecies transmission and pathogenesis. Unlike 2019-nCoV and human SARS-CoV, most known bat SARSr-CoVs have two stretches of deletions in the spike receptor binding domain (RBD) when compared with that of human SARS-CoV. But some Yunnan strains such as the WIV1 had no such deletions and can use human ACE2 as a cellular entry receptor. It is interesting to note that the two bat SARS-related coronavirus ZXC21 and ZC45, being closest to 2019-nCoV, can infect suckling rats and cause inflammation in the brain tissue, and pathological changes in lung \u0026 intestine. However, these two viruses could not be isolated in Vero E6 cells and were not investigated further. The two retained deletion sites in the Spike genes of ZXC21 and ZC45 may lessen their likelihood of jumping species barriers imposed by receptor specificity.\nFigure 2. Comparison of protein sequences of Spike stalk S2 subunit. Multiple alignment of Spike S2 amino acid sequences of 2019-nCoV HKU-SZ-005b (accession number MN975262), bat SARS-like coronavirus isolates bat-SL-CoVZXC21 and bat-SL-CoVZXC45 (accession number MG772934.1 and MG772933.1, respectively) and human SARS coronavirus (accession number NC004718) was performed and displayed using CLUSTAL 2.1 and BOXSHADE 3.21 respectively. The black boxes represent the identity while the grey boxes represent the similarity of the four amino acid sequences. Figure 3. Comparison of protein sequences of A. Spike globular head S1, and B. S1 receptor-binding domain (RBD) subunit. Multiple alignment of Spike S1 amino acid sequences of 2019-nCoV HKU-SZ-005b (accession number MN975262), bat SARS-like coronavirus isolates bat-SL-CoVZXC21, bat-SL-CoVZXC45, bat-SL-CoV-YNLF_31C, bat-SL-CoV-YNLF_34C and bat SL-CoV HKU3-1 (accession number MG772934.1 and MG772933.1, KP886808, KP886809 and DQ022305, respectively), human SARS coronavirus GZ02 and Tor2 (accession number AY390556 and AY274119, respectively) and Paguma SARS-CoV (accession number AY515512) was performed and displayed using CLUSTAL 2.1 and BOXSHADE 3.21, respectively. The black background represents the identity while the grey background represents the similarity of the amino acid sequences. Orange box indicates the region of signal peptide, while green and blue boxes indicate the core domain and receptor binding domain respectively. Sequences of RBD, highlighted in (A) were used for comparison. External subdomain variable region of 2019-nCoV HKU-SZ-005b was predicted by comparison of amino acid similarity and published structural analysis [17]. Purple box indicates the external subdomain 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