Alexander M R, Schoeder C T, Brown J A, Smart C D, Moth C, Wikswo J P, Capra J A, Meiler J, Chen W, Madhur M S
bioRxiv. 2020 Jul 10:2020.07.09.194563. doi: 10.1101/2020.07.09.194563.
In only a few months, the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic, leaving physicians, scientists, and public health officials racing to understand, treat, and contain this zoonotic disease. SARS-CoV-2 has made the leap from animals to humans, but little is known about variations in species susceptibility that could identify potential reservoir species, animal models, and the risk to pets, wildlife, and livestock. While there is evidence that certain species, such as cats, are susceptible, the vast majority of animal species, including those in close contact with humans, have unknown susceptibility. Hence, methods to predict their infection risk are urgently needed. SARS-CoV-2 spike protein binding to angiotensin converting enzyme 2 (ACE2) is critical for viral cell entry and infection. Here we identified key ACE2 residues that distinguish susceptible from resistant species using in-depth sequence and structural analyses of ACE2 and its binding to SARS-CoV-2. Our findings have important implications for identification of ACE2 and SARS-CoV-2 residues for therapeutic targeting and identification of animal species with increased susceptibility for infection on which to focus research and protection measures for environmental and public health.
在短短几个月内,新型冠状病毒严重急性呼吸综合征冠状病毒2(SARS-CoV-2)就引发了一场全球大流行,使得医生、科学家和公共卫生官员竞相去了解、治疗和控制这种人畜共患疾病。SARS-CoV-2已从动物传播到人类,但对于物种易感性的差异知之甚少,而这些差异可能有助于确定潜在的宿主物种、动物模型以及对宠物、野生动物和家畜的风险。虽然有证据表明某些物种,如猫,是易感的,但绝大多数动物物种,包括那些与人类密切接触的物种,其易感性尚不清楚。因此,迫切需要预测它们感染风险的方法。SARS-CoV-2刺突蛋白与血管紧张素转换酶2(ACE2)的结合对于病毒进入细胞和感染至关重要。在此,我们通过对ACE2及其与SARS-CoV-2结合的深入序列和结构分析,确定了区分易感物种和抗性物种的关键ACE2残基。我们的研究结果对于确定用于治疗靶点的ACE2和SARS-CoV-2残基,以及确定易感性增加的动物物种具有重要意义,从而可以针对这些物种开展研究并采取环境保护和公共卫生方面的保护措施。