Abstract

COVID‑19, a new human respiratory disease that has killed nearly 3 million people in a year since the start of the pandemic, is a global public health challenge. Its infectious agent, SARS‑CoV‑2, differs from other coronaviruses in a number of structural features that make this virus more pathogenic and transmissible. In this review, we discuss some important characteristics of the main SARS‑CoV‑2 surface antigen, the spike (S) protein, such as (i) ability of the receptor-binding domain (RBD) to switch between the “standing-up” position (open pre-fusion conformation) for receptor binding and the “lying-down” position (closed pre-fusion conformation) for immune system evasion; (ii) advantage of a high binding affinity of the RBD open conformation to the human angiotensin-converting enzyme 2 (ACE2) receptor for efficient cell entry; and (iii) S protein preliminary activation by the intracellular furin-like proteases for facilitation of the virus spreading across different cell types. We describe interactions between the S protein and cellular receptors, co-receptors, and antagonists, as well as a hypothetical mechanism of the homotrimeric spike structure destabilization that triggers the fusion of the viral envelope with the cell membrane at physiological pH and mediates the viral nucleocapsid entry into the cytoplasm. The transition of the S protein pre-fusion conformation to the post-fusion one on the surface of virions after their treatment with some reagents, such as β-propiolactone, is essential, especially in relation to the vaccine production. We also compare the COVID‑19 pathogenesis with that of severe outbreaks of “avian” influenza caused by the A/H5 and A/H7 highly pathogenic viruses and discuss the structural similarities between the SARS‑CoV‑2 S protein and hemagglutinins of those highly pathogenic strains. Finally, we touch on the prospective and currently used COVID‑19 antiviral and anti-pathogenetic therapeutics, as well as recently approved conventional and innovative COVID‑19 vaccines and their molecular and immunological features.

中文翻译：

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COVID-19：神话与现实

 抽象的

COVID-19 是一种新的人类呼吸道疾病，自大流行开始以来一年内已导致近 300 万人死亡，是一项全球公共卫生挑战。其传染源 SARS-CoV-2 与其他冠状病毒的许多结构特征不同，这些特征使该病毒更具致病性和传播性。在这篇综述中，我们讨论了主要 SARS-CoV-2 表面抗原——刺突 (S) 蛋白的一些重要特征，例如 (i) 受体结合结构域 (RBD) 在“直立”和“直立”之间切换的能力。用于受体结合的“位置（开放的融合前构象）和用于逃避免疫系统的“躺下”位置（闭合的融合前构象）； (ii) RBD 开放构象与人血管紧张素转换酶 2 (ACE2) 受体的高结合亲和力的优势，可有效进入细胞； (iii) S蛋白被细胞内弗林蛋白酶样蛋白酶初步激活，以促进病毒在不同细胞类型之间传播。我们描述了 S 蛋白与细胞受体、共受体和拮抗剂之间的相互作用，以及同源三聚体尖峰结构不稳定的假设机制，该机制在生理 pH 下触发病毒包膜与细胞膜融合并介导病毒核衣壳进入细胞质。在用一些试剂（例如β-丙内酯）处理后，病毒粒子表面的S蛋白融合前构象向融合后构象的转变是至关重要的，特别是在疫苗生产方面。 我们还将 COVID-19 的发病机制与 A/H5 和 A/H7 高致病性病毒引起的“禽”流感严重爆发的发病机制进行了比较，并讨论了 SARS-CoV-2 S 蛋白与高致病性病毒的血凝素之间的结构相似性。致病菌株。最后，我们讨论了前瞻性和当前使用的 COVID-19 抗病毒和抗病原体疗法，以及最近批准的传统和创新的 COVID-19 疫苗及其分子和免疫学特征。