Department of Microbiology and Molecular Genetics, University of California, Davis, CA, USA.
Department of Physics, University of California, Davis, USA.
Sci Rep. 2023 Jun 8;13(1):9319. doi: 10.1038/s41598-023-35861-7.
Establishing the host range for novel viruses remains a challenge. Here, we address the challenge of identifying non-human animal coronaviruses that may infect humans by creating an artificial neural network model that learns from spike protein sequences of alpha and beta coronaviruses and their binding annotation to their host receptor. The proposed method produces a human-Binding Potential (h-BiP) score that distinguishes, with high accuracy, the binding potential among coronaviruses. Three viruses, previously unknown to bind human receptors, were identified: Bat coronavirus BtCoV/133/2005 and Pipistrellus abramus bat coronavirus HKU5-related (both MERS related viruses), and Rhinolophus affinis coronavirus isolate LYRa3 (a SARS related virus). We further analyze the binding properties of BtCoV/133/2005 and LYRa3 using molecular dynamics. To test whether this model can be used for surveillance of novel coronaviruses, we re-trained the model on a set that excludes SARS-CoV-2 and all viral sequences released after the SARS-CoV-2 was published. The results predict the binding of SARS-CoV-2 with a human receptor, indicating that machine learning methods are an excellent tool for the prediction of host expansion events.
确定新型病毒的宿主范围仍然是一个挑战。在这里,我们通过创建一个从α和β冠状病毒的刺突蛋白序列及其与宿主受体结合的注释中学习的人工神经网络模型,来解决鉴定可能感染人类的非人类动物冠状病毒的挑战。所提出的方法产生了一个人类结合潜力(h-BiP)评分,该评分可以准确地区分冠状病毒之间的结合潜力。鉴定出三种以前未知与人类受体结合的病毒:蝙蝠冠状病毒 BtCoV/133/2005 和 Pipistrellus abramus 蝙蝠冠状病毒 HKU5 相关(均与 MERS 相关病毒),以及 Rhinolophus affinis 冠状病毒分离株 LYRa3(与 SARS 相关病毒)。我们进一步使用分子动力学分析了 BtCoV/133/2005 和 LYRa3 的结合特性。为了测试该模型是否可用于新型冠状病毒的监测,我们在一组排除 SARS-CoV-2 和 SARS-CoV-2 发布后发布的所有病毒序列的基础上重新训练了该模型。结果表明,SARS-CoV-2 可以与人类受体结合,这表明机器学习方法是预测宿主扩展事件的绝佳工具。