Immunogenetics and Transplantation Laboratory, Department of Surgery, University of California San Francisco, San Francisco, CA, USA.
BioExIn, Delhi, India.
Sci Rep. 2023 Feb 9;13(1):2351. doi: 10.1038/s41598-022-20773-9.
The high magnitude zoonotic event has caused by Severe Acute Respitarory Syndrome CoronaVirus-2 (SARS-CoV-2) is Coronavirus Disease-2019 (COVID-19) epidemics. This disease has high rate of spreading than mortality in humans. The human receptor, Angiotensin-Converting Enzyme 2 (ACE2), is the leading target site for viral Spike-protein (S-protein) that function as binding ligands and are responsible for their entry in humans. The patients infected with COVID-19 with comorbidities, particularly cancer patients, have a severe effect or high mortality rate because of the suppressed immune system. Nevertheless, there might be a chance wherein cancer patients cannot be infected with SARS-CoV-2 because of mutations in the ACE2, which may be resistant to the spillover between species. This study aimed to determine the mutations in the sequence of the human ACE2 protein and its dissociation with SARS-CoV-2 that might be rejecting viral transmission. The in silico approaches were performed to identify the impact of SARS-CoV-2 S-protein with ACE2 mutations, validated experimentally, occurred in the patient, and reported in cell lines. The identified changes significantly affect SARS-CoV-2 S-protein interaction with ACE2, demonstrating the reduction in the binding affinity compared to SARS-CoV. The data presented in this study suggest ACE2 mutants have a higher and lower affinity with SARS-Cov-2 S-protein to the wild-type human ACE2 receptor. This study would likely be used to report SARS-CoV-2 resistant ACE2 mutations and can be used to design active peptide development to inactivate the viral spread of SARS-CoV-2 in humans.
由严重急性呼吸系统综合症冠状病毒 2 型（SARS-CoV-2）引起的高幅度人畜共患病事件是冠状病毒病 2019（COVID-19）疫情。这种疾病在人类中的传播率高于死亡率。人类受体血管紧张素转换酶 2（ACE2）是病毒刺突蛋白（S 蛋白）的主要靶位，作为结合配体，负责它们在人类中的进入。患有合并症的 COVID-19 患者，特别是癌症患者，由于免疫系统受到抑制，会产生严重影响或高死亡率。然而，由于 ACE2 中的突变，癌症患者可能无法感染 SARS-CoV-2，这可能使其具有抵抗物种间溢出的能力。本研究旨在确定人类 ACE2 蛋白序列中的突变及其与 SARS-CoV-2 的分离，这可能会阻止病毒的传播。进行了计算机模拟方法来确定与 ACE2 突变相关的 SARS-CoV-2 S 蛋白的影响，这些突变在患者中发生，并在细胞系中报告。鉴定出的变化显著影响 SARS-CoV-2 S 蛋白与 ACE2 的相互作用，与 SARS-CoV 相比，显示出结合亲和力的降低。本研究中提出的数据表明，ACE2 突变体与 SARS-Cov-2 S 蛋白的亲和力高于野生型人类 ACE2 受体，也低于野生型人类 ACE2 受体。本研究可能用于报告对 SARS-CoV-2 具有抗性的 ACE2 突变，并可用于设计活性肽开发以抑制 SARS-CoV-2 在人类中的病毒传播。
