Data_Sheet_4_Systematic Tracing of Susceptible Animals to SARS-CoV-2 by a Bioinformatics Framework.FASTA

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型（SARS-CoV-2）暴发以来，中华菊头蝠便被视为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。为实现该高传染性疾病的监测与防控，追踪易感动物并预测病毒刺突蛋白与宿主血管紧张素转换酶2（ACE2）蛋白结合区域的潜在突变所带来的影响，至关重要。本研究提出了一种全新的生物信息学框架，可系统性追踪SARS-CoV-2的易感动物，并预测易感动物体内突变/未突变ACE2受体与病毒的结合亲和力。通过对ACE2蛋白与病毒刺突蛋白进行分子对接分析，本研究鉴定出若干存在SARS-CoV-2感染潜在风险的动物。部分物种与病毒的结合亲和力弱于人类，但强于中华菊头蝠。本研究同时发现，人类ACE2蛋白或病毒刺突蛋白上的若干点突变可显著提升二者的结合亲和力，对公共卫生构成巨大潜在威胁。奥密克戎毒株的祖先可能通过在宿主感染过程中积累突变而快速演化，并实现跨物种传播至人类。上述研究结果表明，若疫情进一步扩散，可能会出现“人-动物-人”的传播链条，进而加大疾病防控的难度。