Elfiky Abdo A, Ibrahim Ibrahim M, Elgohary Alaa M
Biophysics Department, Faculty of Science, Cairo University, Giza, Egypt.
Int J Pept Res Ther. 2022;28(5):146. doi: 10.1007/s10989-022-10450-w. Epub 2022 Aug 22.
Different SARS-CoV-2 new variants emerged and spread during the past few months, sparking infections and death counts. The new variant B.1.617 (delta variant) sparked in India in the past few months, causing the highest records. The B.1.617 variant of SARS-CoV-2 has the double mutations E484Q and L452R on its spike Receptor Binding Domain (RBD). The first mutation is like the reported South African and the Brazilian variants (501.V2 and B.1.1.248). This mutation lies in the region C480-C488, which we predicted before to be recognized by the host-cell receptor; Glucose Regulated Protein 78 (GRP78). In the current study, we test the binding affinity of the host-cell receptor GRP78 to the delta variant spike RBD using molecular docking and molecular dynamics simulations of up to 100 ns. Additionally, the ACE2-RBD is tested by protein-protein docking. The results reveal equal average binding affinities of the GRP78 against wildtype and delta variant spikes. This supports our previous predictions of the contribution of GRP78 in SARS-CoV-2 spike recognition as an auxiliary route for entry.
在过去几个月里，出现了不同的新冠病毒新变种并传播开来，引发了感染和死亡病例数的增加。新变种B.1.617（德尔塔变种）在过去几个月里在印度出现，导致了最高纪录。新冠病毒的B.1.617变种在其刺突受体结合域（RBD）上有E484Q和L452R双重突变。第一个突变类似于已报道的南非和巴西变种（501.V2和B.1.1.248）。这个突变位于C480 - C488区域，我们之前预测该区域会被宿主细胞受体；葡萄糖调节蛋白78（GRP78）识别。在本研究中，我们使用分子对接和长达100纳秒的分子动力学模拟来测试宿主细胞受体GRP78与德尔塔变种刺突RBD的结合亲和力。此外，通过蛋白质 - 蛋白质对接测试ACE2 - RBD。结果显示GRP78对野生型和德尔塔变种刺突的平均结合亲和力相等。这支持了我们之前关于GRP78在新冠病毒刺突识别中作为辅助进入途径的贡献的预测。
