Division of Cancer and Stem Cells, School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham NG7 2RD, U.K.
School of Pharmacy, Biodiscovery Institute, University of Nottingham, Nottingham NG7 2RD, U.K.
Biosci Rep. 2021 Jan 29;41(1). doi: 10.1042/BSR20203837.
ORF7a is an accessory protein common to SARS-CoV1 and the recently discovered SARS-CoV2, which is causing the COVID-19 pandemic. The ORF7a protein has a structural homology with ICAM-1 which binds to the T lymphocyte integrin receptor LFA-1. As COVID-19 has a strong immune component as part of the disease, we sought to determine whether SARS-CoV2 would have a similar structural interaction with LFA-1. Using molecular docking simulations, we found that SARS-CoV2 ORF7a has the key structural determinants required to bind LFA-1 but also the related leukocyte integrin Mac-1, which is also known to be expressed by macrophages. Our study shows that SARS-CoV2 ORF7a protein has a conserved Ig immunoglobulin-like fold containing an integrin binding site that provides a mechanistic hypothesis for SARS-CoV2's interaction with the human immune system. This suggests that experimental investigation of ORF7a-mediated effects on immune cells such as T lymphocytes and macrophages (leukocytes) could help understand the disease further and develop effective treatments.
ORF7a 是 SARS-CoV1 和最近发现的导致 COVID-19 大流行的 SARS-CoV2 共有的辅助蛋白。ORF7a 蛋白与 ICAM-1 具有结构同源性，ICAM-1 与 T 淋巴细胞整合素受体 LFA-1 结合。由于 COVID-19 是疾病的一个重要组成部分，具有强烈的免疫成分，我们试图确定 SARS-CoV2 是否与 LFA-1 具有类似的结构相互作用。通过分子对接模拟，我们发现 SARS-CoV2 ORF7a 具有与 LFA-1 结合所需的关键结构决定因素，但也具有与白细胞整合素 Mac-1 的相关结构决定因素，Mac-1 也已知由巨噬细胞表达。我们的研究表明，SARS-CoV2 ORF7a 蛋白具有保守的 Ig 免疫球蛋白样折叠，包含一个整合素结合位点，为 SARS-CoV2 与人类免疫系统的相互作用提供了一种机制假说。这表明对 ORF7a 介导的对 T 淋巴细胞和巨噬细胞（白细胞）等免疫细胞的影响进行实验研究，可能有助于进一步了解疾病并开发有效的治疗方法。
