An insight into SARS-CoV-2 membrane protein interaction with spike, envelope, and nucleocapsid proteins

Intraviral protein–protein interactions are crucial for replication, pathogenicity, and viral assembly. Among these, virus assembly is a critical step as it regulates the arrangements of viral structural proteins and helps in the encapsulation of genomic material. SARS-CoV-2 structural proteins play an essential role in the self-rearrangement, RNA encapsulation, and mature virus particle formation. In SARS-CoV, the membrane protein interacts with the envelope and spike protein in Endoplasmic Reticulum Golgi Intermediate Complex (ERGIC) to form an assembly in the lipid bilayer, followed by membrane-ribonucleoprotein (nucleocapsid) interaction. In this study, we tried to understand the interaction of membrane protein’s interaction with envelope, spike, and nucleocapsid proteins using protein–protein docking. Further, simulation studies were performed up to 100 ns to examine the stability of protein–protein complexes of Membrane-Envelope, Membrane-Spike, and Membrane-Nucleocapsid proteins. Prime MM-GBSA showed high binding energy calculations for the simulated structures than the docked complex. The interactions identified in our study will be of great importance, as it provides valuable insight into the protein–protein complex, which could be the potential drug targets for future studies. Communicated by Ramaswamy H. Sarma

病毒内蛋白质间相互作用对于病毒复制、致病性以及病毒组装均至关重要。其中，病毒组装是关键步骤，其可调控病毒结构蛋白的排布，并助力基因组物质的衣壳化。严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）的结构蛋白在自身重排、RNA衣壳化以及成熟病毒颗粒形成过程中发挥关键作用。在SARS冠状病毒中，膜蛋白在内质网-高尔基体中间区室（Endoplasmic Reticulum Golgi Intermediate Complex, ERGIC）内与包膜蛋白和刺突蛋白相互作用，于脂质双层中形成组装体，随后发生膜蛋白-核糖核蛋白（核衣壳）的相互作用。本研究通过蛋白质-蛋白质对接技术，探究了膜蛋白与包膜蛋白、刺突蛋白及核衣壳蛋白之间的相互作用。此外，本研究开展了时长高达100纳秒的模拟实验，以评估膜蛋白-包膜蛋白、膜蛋白-刺突蛋白及膜蛋白-核衣壳蛋白复合物的稳定性。Prime MM-GBSA分析显示，模拟得到的复合物结构相较于对接复合物，具有更高的结合能。本研究鉴定得到的相互作用具有重要意义，可为该蛋白质-蛋白质复合物提供宝贵的解析视角，而该复合物有望成为未来研究的潜在药物靶点。由Ramaswamy H. Sarma转交