Khan Abbas, Mohammad Anwar, Haq Inamul, Nasar Mohammad, Ahmad Waqar, Yousafi Qudsia, Suleman Muhammad, Ahmad Sajjad, Albutti Aqel, Khan Taimoor, Marafie Sulaiman K, Alshawaf Eman, Ali Syed Shujait, Abubaker Jehad, Wei Dong-Qing
Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
Department of Biochemistry and Molecular Biology, Dasman Diabetes Institute, Dasman 15462, Kuwait.
Microorganisms. 2021 Nov 11;9(11):2331. doi: 10.3390/microorganisms9112331.
Glucose-regulated protein 78 (GRP78) might be a receptor for SARS-CoV-2 to bind and enter the host cell. Recently reported mutations in the spike glycoprotein unique to the receptor-binding domain (RBD) of different variants might increase the binding and pathogenesis. However, it is still not known how these mutations affect the binding of RBD to GRP78. The current study provides a structural basis for the binding of GRP78 to the different variants, i.e., B.1.1.7, B.1.351, B.1.617, and P.1 (spike RBD), of SARS-CoV-2 using a biomolecular simulation approach. Docking results showed that the new variants bound stronger than the wild-type, which was further confirmed through the free energy calculation results. All-atom simulation confirmed structural stability, which was consistent with previous results by following the global stability trend. We concluded that the increased binding affinity of the B.1.1.7, B.1.351, and P.1 variants was due to a variation in the bonding network that helped the virus induce a higher infectivity and disease severity. Consequently, we reported that the aforementioned new variants use GRP78 as an alternate receptor to enhance their seriousness.
葡萄糖调节蛋白78（GRP78）可能是严重急性呼吸综合征冠状病毒2（SARS-CoV-2）结合并进入宿主细胞的受体。最近报道的不同变体受体结合域（RBD）特有的刺突糖蛋白突变可能会增加其结合能力和致病性。然而，这些突变如何影响RBD与GRP78的结合仍不清楚。本研究使用生物分子模拟方法，为GRP78与SARS-CoV-2的不同变体（即B.1.1.7、B.1.351、B.1.617和P.1（刺突RBD））的结合提供了结构基础。对接结果表明，新变体的结合比野生型更强，这通过自由能计算结果得到了进一步证实。全原子模拟证实了结构稳定性，这与之前遵循全局稳定性趋势的结果一致。我们得出结论，B.1.1.7、B.1.351和P.1变体结合亲和力的增加是由于键合网络的变化，这有助于病毒诱导更高的感染性和疾病严重程度。因此，我们报道上述新变体利用GRP78作为替代受体来增强其严重性。
