RT Journal Article SR Electronic T1 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 JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.03.02.974139 DO 10.1101/2020.03.02.974139 A1 Hong Zhou A1 Xing Chen A1 Tao Hu A1 Juan Li A1 Hao Song A1 Yanran Liu A1 Peihan Wang A1 Di Liu A1 Jing Yang A1 Edward C. Holmes A1 Alice C. Hughes A1 Yuhai Bi A1 Weifeng Shi YR 2020 UL http://biorxiv.org/content/early/2020/03/11/2020.03.02.974139.abstract 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.