Protein Structure and Sequence Reanalysis of 2019-nCoV Genome Refutes Snakes as Its Intermediate Host and the Unique Similarity between Its Spike Protein Insertions and HIV-1.

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

Abstract

As the infection of 2019-nCoV coronavirus is quickly developing into a global pneumonia epidemic, the careful analysis of its transmission and cellular mechanisms is sorely needed. In this Communication, we first analyzed two recent studies that concluded that snakes are the intermediate hosts of 2019-nCoV and that the 2019-nCoV spike protein insertions share a unique similarity to HIV-1. However, the reimplementation of the analyses, built on larger scale data sets using state-of-the-art bioinformatics methods and databases, presents clear evidence that rebuts these conclusions. Next, using metagenomic samples from Manis javanica, we assembled a draft genome of the 2019-nCoV-like coronavirus, which shows 73% coverage and 91% sequence identity to the 2019-nCoV genome. In particular, the alignments of the spike surface glycoprotein receptor binding domain revealed four times more variations in the bat coronavirus RaTG13 than in the Manis coronavirus compared with 2019-nCoV, suggesting the pangolin as a missing link in the transmission of 2019-nCoV from bats to human.

Supporting text Virus Host Location
2019-nCoV 5 Malayan pangolins 1 metagenome assembly 1 spike protein 32 Host-Pathogen Interactions 55 Models, Molecular 99 Amino Acid Sequence 128 Animals 1949 Betacoronavirus 78 Coronavirus Infections 171 COVID-19 425 Eutheria 9 Genome, Viral 317 HIV-1 11 Humans 1441 Metagenome 4 Pandemics 108 Pneumonia, Viral 42 Protein Structure, Tertiary 29 SARS-CoV-2 453 Sequence Alignment 51 Sequence Analysis, Protein 9 Snakes 2 Spike Glycoprotein, Coronavirus 274

Evidence records

2 total
Zoonotic Surveillance
1 records · 1 evidence types
Evidence type
1 records
OVE3680
Key finding

A 2019-nCoV-like coronavirus genome was detected and assembled from metagenomic samples of Manis javanica with 73% coverage and 91% sequence identity to 2019-nCoV.

Virus
Host
Location
Not specified
Supporting text

Next, using metagenomic samples from Manis javanica, we assembled a draft genome of the 2019-nCoV-like coronavirus, which shows 73% coverage and 91% sequence identity to the 2019-nCoV genome.

Method
metagenomic sequencing | genome assembly
Sample type
metagenomic samples
Genomic Evolution
1 records · 1 evidence types
Evidence type
1 records
OVE3681
Key finding

Comparative sequence analysis suggests a coronavirus related to 2019-nCoV was transmitted between bats and pangolins.

Virus
Host
Location
Not specified
Supporting text

The alignments of the spike surface glycoprotein receptor binding domain revealed four times more variations in the bat coronavirus RaTG13 than in the Manis coronavirus compared with 2019-nCoV, suggesting the pangolin as a missing link in the transmission of 2019-nCoV from bats to human.

Analysis methods
sequence alignment | receptor binding domain comparison