SARS-CoV-2 spike protein predicted to form complexes with host receptor protein orthologues from a broad range of mammals.
SARS-CoV-2 spike protein predicted to form complexes with host receptor protein orthologues from a broad range of mammals.
复制标题
DOI：
10.1038/s41598-020-71936-5
复制
发表时间：
2020-10-05
影响因子：
4.6
通讯作者：
Orengo CA
中科院分区：
文献类型：
--
作者：
Lam SD;Bordin N;Waman VP;Scholes HM;Ashford P;Sen N;van Dorp L;Rauer C;Dawson NL;Pang CSM;Abbasian M;Sillitoe I;Edwards SJL;Fraternali F;Lees JG;Santini JM;Orengo CA
SARS-CoV-2具有人畜共患起源，并通过未确定的中间宿主传播给人类，导致人类和其他哺乳动物感染。为了进入宿主细胞，病毒刺突蛋白（S蛋白）与其受体ACE 2结合，然后由TMPRSS 2加工。虽然受体结合有助于病毒宿主范围，但来自其他动物的S-蛋白：ACE 2复合物尚未得到广泛研究。为了预测感染风险，我们对来自215种脊椎动物物种的S蛋白：ACE 2复合物进行了建模，计算了每个物种中突变引起的复合物相对于人类ACE 2的能量变化，并将这些变化与COVID-19感染数据相关联。我们还分析了结构相互作用，以更好地了解有助于亲和力的关键残基。我们预测突变在ACE 2中比TMPRSS 2更有害。最后，我们证明了人类SARS-CoV-2病毒株已在动物中分离。我们的研究结果表明，SARS-CoV-2可以感染广泛的哺乳动物，但很少有鱼类，鸟类或爬行动物。易感动物可能成为病毒的宿主，因此需要对动物进行持续的仔细管理和监测。
SARS-CoV-2 has a zoonotic origin and was transmitted to humans via an undetermined intermediate host, leading to infections in humans and other mammals. To enter host cells, the viral spike protein (S-protein) binds to its receptor, ACE2, and is then processed by TMPRSS2. Whilst receptor binding contributes to the viral host range, S-protein:ACE2 complexes from other animals have not been investigated widely. To predict infection risks, we modelled S-protein:ACE2 complexes from 215 vertebrate species, calculated changes in the energy of the complex caused by mutations in each species, relative to human ACE2, and correlated these changes with COVID-19 infection data. We also analysed structural interactions to better understand the key residues contributing to affinity. We predict that mutations are more detrimental in ACE2 than TMPRSS2. Finally, we demonstrate phylogenetically that human SARS-CoV-2 strains have been isolated in animals. Our results suggest that SARS-CoV-2 can infect a broad range of mammals, but few fish, birds or reptiles. Susceptible animals could serve as reservoirs of the virus, necessitating careful ongoing animal management and surveillance.