论文标题
SARS-COV-2组装的生物物理模型：基因组凝结和萌芽
Biophysical Modeling of SARS-CoV-2 Assembly: Genome Condensation and Budding
论文作者
论文摘要
由严重的急性呼吸综合症2（SARS-COV-2）引起的19009年大流行刺激了前所未有的全球研究，以减少和消除这种病原体。 SARS-COV-2具有四种结构蛋白：包膜（E），膜（M），Nucleocapsid（n）和Spike（S），它们通过从细胞内脂质膜上萌芽而自组装及其RNA与感染性病毒。在本文中，我们开发了一个模型，以探索通过结构蛋白，蛋白质低聚和细胞膜 - 蛋白质相互作用来控制RNA缩合的机制，从而控制了萌芽过程和最终的病毒结构。使用分子动力学模拟，我们已经解释了带正电的N蛋白如何相互作用并凝结的非常长的基因组RNA，从而通过脂质信封包装了其包装，该脂质包膜在宿主细胞内装饰有结构蛋白。此外，考虑到RNA的长度和病毒的大小，我们发现M蛋白的内在曲率对于病毒萌芽至关重要。尽管当前的大多数研究都集中在造成病毒的S蛋白上，并且由于需要开发有效的疫苗的需要，但通过这种关键蛋白质中突变的耐药性发展，这对于阐明病毒生命周期的细节以识别其他药物的其他药物对未来的治疗至关重要。我们的模拟将通过从头开始的病毒颗粒组装来洞悉病毒生命周期，并有可能确定未来药物发育的治疗靶标。
The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spurred unprecedented and concerted worldwide research to curtail and eradicate this pathogen. SARS-CoV-2 has four structural proteins: Envelope (E), Membrane (M), Nucleocapsid (N), and Spike (S), which self-assemble along with its RNA into the infectious virus by budding from intracellular lipid membranes. In this paper, we develop a model to explore the mechanisms of RNA condensation by structural proteins, protein oligomerization and cellular membrane-protein interactions that control the budding process and the ultimate virus structure. Using molecular dynamics simulations, we have deciphered how the positively charged N proteins interact and condense the very long genomic RNA resulting in its packaging by a lipid envelope decorated with structural proteins inside a host cell. Furthermore, considering the length of RNA and the size of the virus, we find that the intrinsic curvature of M proteins is essential for virus budding. While most current research has focused on the S protein, which is responsible for viral entry, and it has been motivated by the need to develop efficacious vaccines, the development of resistance through mutations in this crucial protein makes it essential to elucidate the details of the viral life cycle to identify other drug targets for future therapy. Our simulations will provide insight into the viral life cycle through the assembly of viral particles de novo and potentially identify therapeutic targets for future drug development.
