PT  - JOURNAL ARTICLE
AU  - Hong Zhou
AU  - Xing Chen
AU  - Tao Hu
AU  - Juan Li
AU  - Hao Song
AU  - Yanran Liu
AU  - Peihan Wang
AU  - Di Liu
AU  - Jing Yang
AU  - Edward C. Holmes
AU  - Alice C. Hughes
AU  - Yuhai Bi
AU  - Weifeng Shi
TI  - A novel bat coronavirus reveals natural insertions at the S1/S2 cleavage site of the Spike protein and a possible recombinant origin of HCoV-19
AID  - 10.1101/2020.03.02.974139
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.03.02.974139
4099  - http://biorxiv.org/content/early/2020/03/06/2020.03.02.974139.short
4100  - http://biorxiv.org/content/early/2020/03/06/2020.03.02.974139.full
AB  - The unprecedented epidemic of pneumonia caused by a novel coronavirus, HCoV-19, in China and beyond has caused public health concern at a global scale. Although bats are regarded as the most likely natural hosts for HCoV-191,2, the origins of the virus remain unclear. Here, we report a novel bat-derived coronavirus, denoted RmYN02, identified from a metagenomics analysis of samples from 227 bats collected from Yunnan Province in China between May and October, 2019. RmYN02 shared 93.3% nucleotide identity with HCoV-19 at the scale of the complete virus genome and 97.2% identity in the 1ab gene in which it was the closest relative of HCoV-19. In contrast, RmYN02 showed low sequence identity (61.3%) to HCoV-19 in the receptor binding domain (RBD) and might not bind to angiotensin-converting enzyme 2 (ACE2). Critically, however, and in a similar manner to HCoV-19, RmYN02 was characterized by the insertion of multiple amino acids at the junction site of the S1 and S2 subunits of the Spike (S) protein. This provides strong evidence that such insertion events can occur in nature. Together, these data suggest that HCoV-19 originated from multiple naturally occurring recombination events among those viruses present in bats and other wildlife species.