Protein structure and sequence re-analysis of 2019-nCoV genome does not indicate snakes as its intermediate host or the unique similarity between its spike protein insertions and HIV-1

Chengxin Zhang; Wei Zheng; Xiaoqiang Huang; Eric W. Bell; Xiaogen Zhou; Yang Zhang

mber of identical residues divided by query length. Only the sequence portion aligned to the query is shown. In this table, we also list the closest BLAST hit from bat coronavirus, which is known to be closely related to 2019-nCoV 1 . Given that 3 out of the 4 insertion fragments are found in the bat coronavirus RaTG13, it is attempting to assume that these "insertions" may be directly inherited from bat coronaviruses. Currently, there are at least 7 known human coronaviruses (2019-nCoV, SARS-CoV, MERS-CoV, HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1), where many of them, including Severe Acute Respiratory Syndrome-related Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome-related Coronavirus (MERS-CoV), were shown to be transmitted from bat [10] [11] [12] [13] [14] (Figure 3A) . To further examine the evolutionary relationship between the 2019-nCoV genome and the bat coronavirus, in comparison with other human coronaviruses, in Figure 3B we created by MUSCLE a multiple sequence alignment (MSA) for all the 7 human coronaviruses and the bat coronavirus RaTG13 that is currently known to be the closest relative to 2019-nCoV 14 among known coronaviruses. Among the 4 "insertions" of the 2019-nCoV, IS1 has only 1 residue different from the bat coronavirus, and 3 out of 7 residues are identical with MERS-CoV. IS2 and IS3 are all identical to the bat coronavirus. For IS4, although the local sequence alignment by BLAST did not hit the bat coronavirus in Table 4 , it has a close evolutionary relation with the bat coronavirus in the MSA. In particular, the first 6 residues in the IS4 fragment "QTQTNSPRRA" from 2019-nCoV are identical to the bat CoV, while the last 4 residues, which were absent in the bat coronavirus or SARS-CoV, have at least 50% identity to MERS-CoV and HCoV-HKU1.