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解码新冠病毒变体:突变、病毒稳定性以及疫苗和治疗方法的突破

Decoding SARS-CoV-2 variants: Mutations, viral stability, and breakthroughs in vaccines and therapies.

作者信息

Abduljaleel Zainularifeen

机构信息

Faculty of Medicine, Department of Medical Genetics, Umm Al-Qura University, P.O. Box 715, Makkah 21955, Saudi Arabia.

出版信息

Biophys Chem. 2025 May-Jun;320-321:107413. doi: 10.1016/j.bpc.2025.107413. Epub 2025 Feb 20.

Abstract

This study investigates the infectivity of SARS-CoV-2 and its immune evasion mechanisms, particularly through mutations in the spike protein that enable the virus to escape host immune responses. As global vaccination efforts continue, understanding viral evolution and immune evasion strategies remains critical. This analysis focuses on fourteen key mutations (Arg346Lys, Lys417Asp, Leu452Glu, Leu452Arg, Phe456Leu, Ser477Asp, Thr478Lys, Glu484Ala, Glu484Lys, Glu484Gln, Gln493Arg, Gly496Ser, Glu498Arg, and His655Y) within the receptor-binding domain (RBD) of the spike protein. The results reveal consistent patterns of immune escape across various SARS-CoV-2 variants, with specific mutations influencing protein stability, binding affinity to the hACE2 receptor, and antibody recognition. These findings demonstrate how single-point mutations can destabilize the spike protein and reduce the efficacy of the immune response. By correlating expression levels and thermodynamic stability with immune evasion, this study provides valuable insights into the functional characteristics of the spike protein. The findings contribute to the understanding of immune escape variants and identify potential targets for enhancing vaccine efficacy and developing therapeutic approaches in response to the evolving SARS-CoV-2 landscape. SHORT SUMMARY: The study investigates the infectivity of SARS-CoV-2 and its implications for immune evasion. It focuses on fourteen key mutations within the spike protein's Receptor-Binding Domain (S-RBD) and reveals consistent patterns associated with immune escape in various SARS-CoV-2 variants. The research highlights the influence of factors such as protein fold stability, hACE2 binding, and antibody evasion on spike protein evolution. Single-point immune escape variants alter virus stability, impacting antibody response success. The study provides valuable insights into immune escape variants and suggests avenues for enhancing vaccine efficacy. It also opens the way for novel therapeutic approaches in the context of SARS-CoV-2 variants.

摘要

本研究调查了严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的传染性及其免疫逃逸机制,特别是通过刺突蛋白中的突变,这些突变使病毒能够逃避宿主免疫反应。随着全球疫苗接种工作的持续推进,了解病毒进化和免疫逃逸策略仍然至关重要。该分析聚焦于刺突蛋白受体结合域(RBD)内的十四个关键突变(精氨酸346突变为赖氨酸、赖氨酸417突变为天冬氨酸、亮氨酸452突变为谷氨酸、亮氨酸452突变为精氨酸、苯丙氨酸456突变为亮氨酸、丝氨酸477突变为天冬氨酸、苏氨酸478突变为赖氨酸、谷氨酸484突变为丙氨酸、谷氨酸484突变为赖氨酸、谷氨酸484突变为谷氨酰胺、谷氨酰胺493突变为精氨酸、甘氨酸496突变为丝氨酸、谷氨酸498突变为精氨酸以及组氨酸655突变为酪氨酸)。结果揭示了不同SARS-CoV-2变体中一致的免疫逃逸模式,特定突变会影响蛋白质稳定性、与人类血管紧张素转换酶2(hACE2)受体的结合亲和力以及抗体识别。这些发现表明单点突变如何使刺突蛋白不稳定并降低免疫反应的效力。通过将表达水平和热力学稳定性与免疫逃逸相关联,本研究为刺突蛋白的功能特性提供了有价值的见解。这些发现有助于理解免疫逃逸变体,并确定增强疫苗效力和针对不断演变的SARS-CoV-2形势开发治疗方法的潜在靶点。简短摘要:该研究调查了SARS-CoV-2的传染性及其对免疫逃逸的影响。它聚焦于刺突蛋白受体结合域(S-RBD)内的十四个关键突变,并揭示了不同SARS-CoV-2变体中与免疫逃逸相关的一致模式。该研究突出了蛋白质折叠稳定性、hACE2结合和抗体逃避等因素对刺突蛋白进化的影响。单点免疫逃逸变体会改变病毒稳定性,影响抗体反应的成效。该研究为免疫逃逸变体提供了有价值的见解,并提出了增强疫苗效力的途径。它还为针对SARS-CoV-2变体的新型治疗方法开辟了道路。

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