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

Due to the scarcity of experimental and clinical data, as well as the urgency to understand the infectivity of the deadly coronaviruses, we have been increasingly relying on computational analyses to study the 2019-nCoV virus in terms of protein structures, functions, phylogeny, and interactions at both molecular and organismal levels. Indeed, within less than a month of the publication of the 2019-nCoV genome in January 2020, multiple bioinformatics analyses regarding 2019-nCoV have been either published or posted as preprint. While such expeditious analyses provide much needed insights into the biology of the 2019-nCoV virus, there is a caution to avoid over-interpretation of the data at the absence of comprehensive benchmarks or follow-up experimental validations. In this report, we have investigated two recently published computational analyses regarding intermediate host identification and the analysis of spike protein insertions. In both cases, we found that the conclusions proposed by the original studies do not hold in the face of more comprehensive replications of these analyses. We hope our analysis presented herein can clarify some of the misinterpretations resulted from previous bioinformatics analyses for the 2019-nCoV virus. the protein, the DEMO pipeline 8 was then used to re-assembly the domains and to construct a complex structure consisting of spike trimer and the extracellular domain of human ACE2, using the ACE2-bound conformation 2 of SARS-CoV spike glycoprotein (PDB ID: 6ACJ) as a template. Our complex modeling did not use the template originally used in the Pradhan et al. study (PDB ID: 6ACD) because it did not include the ACE2 receptor.