A novel bat coronavirus with a polybasic furin-like cleavage site

The current pandemic of COVID-19 caused by a novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), threatens human health around the world. Of particular concern is that bats are recognized as one of the most potential natural hosts of SARS-CoV-2; however, coronavirus ecology in bats is still nascent. Here, we performed a degenerate primer screening and next-generation sequencing analysis of 112 bats, collected from Hainan Province, China. Three coronaviruses, namely bat betacoronavirus (Bat CoV) CD35, Bat CoV CD36 and bat alphacoronavirus CD30 were identified. Bat CoV CD35 genome had 99.5% identity with Bat CoV CD36, both sharing the highest nucleotide identity with Bat Hp-betacoronavirus Zhejiang2013 (71.4%), followed by SARS-CoV-2 (54.0%). Phylogenetic analysis indicated that Bat CoV CD35 formed a distinct clade, and together with Bat Hp-betacoronavirus Zhejiang2013, was basal to the lineage of SARS-CoV-1 and SARS-CoV-2. Notably, Bat CoV CD35 harbored a canonical furin-like S1/S2 cleavage site that resembles the corresponding sites of SARS-CoV-2. The furin cleavage sites between CD35 and CD36 are identical. In addition, the receptor-binding domain of Bat CoV CD35 showed a highly similar structure to that of SARS-CoV-1 and SARS-CoV-2, especially in one binding loop. In conclusion, this study deepens our understanding of the diversity of coronaviruses and provides clues about the natural origin of the furin cleavage site of SARS-CoV-2.