PMC:7079563 / 15532-20186 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7079563","sourcedb":"PMC","sourceid":"7079563","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7079563","text":"3.2 Receptor usage of 2019-nCoV\nThe prerequisite of coronaviruses invading the host-cell is to bind to receptors. Following receptor binding, the viral spike protein is cleaved via acid-dependent proteolysis by cathepsin, TMPRRS2 or furin protease, followed by fusion of the viral envelop to the cellular membranes. Spike is a large, clove-shaped trimer, which can be cleaved by proteases into an N-terminal S1 subunit containing the receptor binding domain (RBD) and a C-terminal S2 region. Compared to other proteins of coronavirus, the spike protein has the most variable amino acid sequences which results from the strongest positive selection among all genes of coronavirus to adapt to its hosts [27].The RBD is a major determinant of host range and cross-species transmission. Recently results showed that 2019-nCoV uses the same cell entry receptor, ACE2, as SARS-CoV [21,24,20,28]. Besides human ACE2, 2019-nCoV can use Chinese horseshoe bats, civet, or pig ACE2 but not mouse ACE2 as an entry receptor [24]. One explanation is that human ACE2 has high homology with Chinese horseshoe bats, civet, pig and mouse, which are 80.75%, 83.48%, 81.37%, 82.11% respectively (Table 2 ), while the residues 82 and 353 of mouse ACE2 are different from human ACE2 which are important residues for bind to spike [29]. But the homology of human ACE2 and pangolin ACE2, cat ACE2 are also high with 84.84% and 85.22%. The homology of human ACE2 with other ACE2 varies from 59.73% to 83.23%. In summary, 2019-nCoV may have extensive host ranges. Fig. 2 .\nTable 2 The amino acid sequence identities of ACE2 among different species.\nSpecies Pairwise identities (%) of the amino acid sequences of ACE2\nAfrican green monkey Civet Bat (R. sinicus) Swine Malayan pangolin Mouse Cat Camel Goat Bos mutus Erinaceus europaeus Cavia porcellus Phascolarctos cinereus Sarcophilus harrisii Tiger Snake Parus major Gallus gallus\nHuman 93.93 83.48 80.75 81.37 84.84 82.11 85.22 83.23 81.61 81.24 79.01 77.29 71.17 70.51 59.73 67.08 65.31\nAfrican green monkey 81.78 79.93 79.93 83.77 81.78 83.15 81.91 81.41 80.92 77.94 76.85 70.38 69.84 59.21 65.6 64.13\nCivet 81.78 81.49 82.73 85.59 81.61 93.29 83.85 81.86 81.74 79.75 75.55 71.66 71.63 59.6 67.44 66.3\nBat (R. sinicus) 79.93 81.49 80 82.86 78.26 83.73 81.37 80.37 80 78.51 74.56 69.68 70.02 58.61 65.11 65.19\nSwine 79.93 82.73 80 82.61 80.62 83.98 89.81 87.7 87.58 77.64 75.3 71.17 71.01 61.09 66.95 65.56\nMalayan pangolin 83.77 85.59 82.86 82.61 82.73 87.33 84.72 82.11 81.86 80.87 77.17 71.66 70.89 59.6 67.44 65.07\nMouse 81.78 81.61 78.26 80.62 82.73 81.74 80.99 80.12 80.37 78.63 78.16 71.05 71.13 61.21 67.2 66.17\nCat 83.15 93.29 83.73 83.98 87.33 81.74 85.71 83.23 83.11 81.49 76.42 72.65 72.25 59.6 67.81 66.79\nCamel 81.91 83.85 81.37 89.81 84.72 80.99 85.71 88.2 88.57 79.25 77.29 71.79 72.12 61.34 67.2 66.42\nGoat 81.41 81.86 80.37 87.7 82.11 80.12 83.23 88.2 97.76 78.14 76.54 72.04 71.38 60.84 66.09 65.44\nBos mutus 80.92 81.74 80 87.58 81.86 80.37 83.11 88.57 97.76 78.39 77.04 71.42 71.01 61.09 66.09 65.31\nErinaceus europaeus 77.94 79.75 78.51 77.64 80.87 78.63 81.49 79.25 78.14 78.39 74.56 70.67 69.65 60.59 68.8 66.42\nCavia porcellus 76.85 75.55 74.56 75.3 77.17 78.16 76.42 77.29 76.54 77.04 74.56 66.61 66.82 59.38 63.9 63.12\nPhascolarctos cinereus 70.38 71.66 69.68 71.17 71.66 71.05 72.65 71.79 72.04 71.42 70.67 66.61 81.92 60.7 67.08 64.83\nSarcophilus harrisii 69.84 71.63 70.02 71.01 70.89 71.13 72.25 72.12 71.38 71.01 69.65 66.82 81.92 60.9 64.62 63.84\nTiger Snake 59.21 59.6 58.61 61.09 59.6 61.21 59.6 61.34 60.84 61.09 60.59 59.38 60.7 60.9 64.5 63.71\nParus major 65.6 67.44 65.11 66.95 67.44 67.2 67.81 67.2 66.09 66.09 68.8 63.9 67.08 64.62 64.5 82.2\nGallus gallus 64.13 66.3 65.19 65.56 65.07 66.17 66.79 66.42 65.44 65.31 66.42 63.12 64.83 63.84 63.71 82.2\nAccession numbers: human (NP_068576.1), monkey (AY996037.1), civet (AAX63775.1), bat (R.sinicus) (AGZ48803.1), swine (NP_001116542.1), Malayan pangolin (XP_017505752.1), mouse (NP_001123985.1), cat (NP_001034545.1), camel (XP_010991717.1), goat (NP_001277036.1), Bos mutus (XP_005903173.1), Erinaceus europaeus (XP_007538670.1), Phascolarctos cinereus (XP_020863153.1), Sarcophilus harrisii (XP_031814825.1), tiger Snake (XP_026530754.1), Parus major (XP_015486815.1), Gallus gallus (QEQ50331.1).\nFig. 2 Phylogenetic analysis of ACE2 from humans and 18 other animals. The tree was constructed based on the complete amino acid sequences of ACE2s derived from humans and other animals by using the neighbor-joining (NJ) method with 1000 bootstrap. The accession numbers were as the same as Table 2. Bootstrap values above 50 were 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