Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela.
Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Virus Res. 2020 Nov;289:198154. doi: 10.1016/j.virusres.2020.198154. Epub 2020 Sep 9.
Recent reports have shown that small and big felines could be infected by SARS-CoV-2, while other animals, like swines and mice, are apparently not susceptible to this infection. These findings raise the question of the role of cell factors associated with early stages of the viral infection in host selectivity. The cellular receptor for SARS-CoV-2 is the Angiotensin Converting Enzyme (ACE2). Transmembrane protease serine 2 (TMPRSS2) has been shown to prime the viral spike for its interaction with its receptor. GRP78 has also been proposed as a possible co-receptor. In this study, we used several bioinformatics approaches to bring clues in the interaction of ACE2, TMPRSS2, and GRP78 with SARS-CoV-2. We selected several mammalian hosts that could play a key role in viral spread by acting as secondary hosts (cats, dogs, pigs, mice, and ferrets) and evaluated their predicted permissiveness by in silico analysis. Results showed that ionic pairs (salt bridges, N-O pair, and long-range interactions) produced between ACE2 and the viral spike has an essential function in the host interaction. On the other hand, TMPRSS2 and GRP78 are proteins with high homology in all the evaluated hosts. Thus, these proteins do not seem to play a role in host selectivity, suggesting that other factors may play a role in the non-permissivity in some of these hosts. These proteins represent however interesting cell targets that could be explored in order to control the virus replication in humans and in the intermediary hosts.
最近的报告表明，小型和大型猫科动物可能会感染 SARS-CoV-2，而其他动物，如猪和老鼠，显然不易感染这种病毒。这些发现提出了一个问题，即与病毒感染早期阶段相关的细胞因子在宿主选择性中的作用。SARS-CoV-2 的细胞受体是血管紧张素转换酶（ACE2）。已表明跨膜丝氨酸蛋白酶 2（TMPRSS2）可使病毒刺突蛋白为与其受体相互作用做好准备。GRP78 也被提议为可能的共受体。在这项研究中，我们使用了几种生物信息学方法来揭示 ACE2、TMPRSS2 和 GRP78 与 SARS-CoV-2 的相互作用。我们选择了几种可能通过充当次要宿主（猫、狗、猪、老鼠和雪貂）在病毒传播中发挥关键作用的哺乳动物宿主，并通过计算机分析评估它们的预测易感性。结果表明，ACE2 和病毒刺突之间产生的离子对（盐桥、N-O 对和远程相互作用）在宿主相互作用中具有重要功能。另一方面，TMPRSS2 和 GRP78 是所有评估宿主中具有高度同源性的蛋白质。因此，这些蛋白质似乎在宿主选择性中不起作用，这表明其他因素可能在其中一些宿主的非许可性中起作用。然而，这些蛋白质代表了有趣的细胞靶标，可以探索它们以控制人类和中间宿主中的病毒复制。
