S2 Subunit of SARS-CoV-2 Spike Protein Induces Domain Fusion in Natural Pulmonary Surfactant Monolayers
S2 Subunit of SARS-CoV-2 Spike Protein Induces Domain Fusion in Natural Pulmonary Surfactant Monolayers
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DOI：
10.1021/acs.jpclett.2c01998
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发表时间：
2022-08
期刊：
影响因子：
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通讯作者：
Xiaojie Xu;Guangle Li;Bingbing Sun;Y. Zuo
中科院分区：
文献类型：
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作者：
Xiaojie Xu;Guangle Li;Bingbing Sun;Y. Zuo
肺表面活性物质已被尝试作为治疗COVID-19的支持疗法。虽然它是机械上接受的S蛋白的S2亚基中的融合肽在介导病毒与宿主细胞膜融合中起着主导作用，它仍然是未知的S2亚基如何与天然表面活性剂膜相互作用。结合生物物理化学分析和原子力显微镜成像，发现S2亚基抑制表面活性剂的生物物理性质，并诱导表面活性剂单层中的微区融合。表面活性剂的抑制作用归因于其融合肽介导的S2亚基的插入所引起的膜流化。这些发现可能为理解表面活性剂与SARS-CoV-2相互作用的生物物理化学机制提供新的见解，并可能对COVID-19患者的表面活性剂替代疗法的进一步开发具有翻译意义。
Pulmonary surfactant has been attempted as a supportive therapy to treat COVID-19. Although it is mechanistically accepted that the fusion peptide in the S2 subunit of the S protein plays a predominant role in mediating viral fusion with the host cell membrane, it is still unknown how the S2 subunit interacts with the natural surfactant film. Using combined bio-physicochemical assays and atomic force microscopy imaging, it was found that the S2 subunit inhibited the biophysical properties of the surfactant and induced microdomain fusion in the surfactant monolayer. The surfactant inhibition has been attributed to membrane fluidization caused by insertion of the S2 subunit mediated by its fusion peptide. These findings may provide novel insight into the understanding of bio-physicochemical mechanisms responsible for surfactant interactions with SARS-CoV-2 and may have translational implications in the further development of surfactant replacement therapy for COVID-19 patients.