Data_Sheet_1_Systematic Tracing of Susceptible Animals to SARS-CoV-2 by a Bioinformatics Framework.CSV

Since the outbreak of SARS-CoV-2 in 2019, the Chinese horseshoe bats were considered as a potential original host of SARS-CoV-2. In addition, cats, tigers, lions, mints, and ferrets were naturally or experimentally infected with SARS-CoV-2. For the surveillance and control of this highly infectious disease, it is critical to trace susceptible animals and predict the consequence of potential mutations at the binding region of viral spike protein and host ACE2 protein. This study proposed a novel bioinformatics framework to systematically trace susceptible animals to SARS-CoV-2 and predict the binding affinity between susceptible animals’ mutated/un-mutated ACE2 receptors. As a result, we identified a few animals posing a potential risk of infection with SARS-CoV-2 using the docking analysis of ACE2 protein and viral spike protein. The binding affinity of some of these species is weaker than that of humans but more potent than that of Chinese horseshoe bats. We also found that a few point mutations in human ACE2 protein or viral spike protein could significantly enhance their binding affinity, posing an enormous potential threat to public health. The ancestors of the Omicron may evolve rapidly through the accumulation of mutations in infecting the host and jumped into human beings. These findings indicate that if the epidemic expands, there may be a human-animal-human transmission route, which will increase the difficulty of disease prevention and control.

自2019年严重急性呼吸综合征冠状病毒2（SARS-CoV-2）暴发以来，中华菊头蝠（Chinese horseshoe bats）被认为是该病毒的潜在自然宿主。此外，猫、虎、狮、水貂及雪貂均已被证实可自然感染或经实验感染SARS-CoV-2。为对这一高传染性疾病开展监测与防控，溯源易感动物并预测病毒刺突蛋白（spike protein）与宿主血管紧张素转换酶2（ACE2，Angiotensin-converting enzyme 2）结合区域的潜在突变后果，具有至关重要的意义。本研究提出了一种全新的生物信息学框架，能够系统溯源SARS-CoV-2的易感动物，并预测易感动物体内突变/未突变的ACE2受体与病毒的结合亲和力。研究通过ACE2蛋白与病毒刺突蛋白的分子对接分析，鉴定出若干存在SARS-CoV-2感染潜在风险的动物。其中部分物种的结合亲和力弱于人类，但强于中华菊头蝠。我们还发现，人类ACE2蛋白或病毒刺突蛋白中的若干点突变可显著增强二者的结合亲和力，对公共卫生构成巨大潜在威胁。奥密克戎（Omicron）的祖先毒株可能通过在感染宿主过程中积累突变而快速演化，并跨物种传播至人类。上述研究结果表明，若疫情进一步扩散，或出现“人-动物-人”的传播途径，这将大幅提升疾病防控的难度。