Inhibition of SARS-CoV-2 wild-type (Wuhan-Hu-1) and Delta (B.1.617.2) strains by marine sulfated glycans.
Inhibition of SARS-CoV-2 wild-type (Wuhan-Hu-1) and Delta (B.1.617.2) strains by marine sulfated glycans.
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DOI：
10.1093/glycob/cwac042
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发表时间：
2022-09-19
期刊：
影响因子：
4.3
通讯作者：
中科院分区：
文献类型：
--
作者：
冠状病毒大流行已将全球治疗研究的努力转向发现潜在的抗严重急性呼吸综合征冠状病毒（SARS-CoV-2）分子。病毒刺突糖蛋白（s蛋白）通过与宿主细胞表面硫酸肝素蛋白聚糖（HSPG）和血管紧张素转换酶-2结合的能力，在SARS-CoV-2感染中已明确确立其作用。针对这两种病毒受体的抗病毒策略目前正在深入研究中。然而，SARS-CoV-2基因组的快速进化导致了s蛋白的大量突变，这给s蛋白靶向抑制剂的设计带来了重大挑战。例如，SARS-CoV-2 Delta变体（B.1.617.2）中s蛋白受体结合域（RBD）的两个关键突变L452R和T478K使其与宿主上皮细胞的结合更加紧密。海洋硫酸聚糖（MSGs）通过竞争性破坏s蛋白RBD-HSPG相互作用，对SARS-CoV-2表现出良好的抑制活性，因此有可能发展成为有效的预防和治疗分子。本研究利用野生型（Wuhan-Hu-1）或Delta (B.1.617.2) s蛋白包被的SARS-CoV-2假病毒，对7种不同的msg抗SARS-CoV-2活性进行了评估。虽然所有测试的味精对两种病毒都有很强的抑制活性，但没有发现味精结构特征与病毒抑制之间的相关性。尽管如此，目前的研究为msg维持对进化中的SARS-CoV-2菌株的抑制活性提供了证据。
The Coronavirus disease pandemic has steered the global therapeutic research efforts toward the discovery of potential anti-severe acute respiratory syndrome coronavirus (SARS-CoV-2) molecules. The role of the viral spike glycoprotein (S-protein) has been clearly established in SARS-CoV-2 infection through its capacity to bind to the host cell surface heparan sulfate proteoglycan (HSPG) and angiotensin-converting enzyme-2. The antiviral strategies targeting these 2 virus receptors are currently under intense investigation. However, the rapid evolution of the SARS-CoV-2 genome has resulted in numerous mutations in the S-protein posing a significant challenge for the design of S-protein-targeted inhibitors. As an example, the 2 key mutations in the S-protein receptor-binding domain (RBD), L452R, and T478K in the SARS-CoV-2 Delta variant (B.1.617.2) confer tighter binding to the host epithelial cells. Marine sulfated glycans (MSGs) demonstrate excellent inhibitory activity against SARS-CoV-2 via competitive disruption of the S-protein RBD-HSPG interactions and thus have the potential to be developed into effective prophylactic and therapeutic molecules. In this study, 7 different MSGs were evaluated for their anti-SARS-CoV-2 activity in a virus entry assay utilizing a SARS-CoV-2 pseudovirus coated with S-protein of the wild-type (Wuhan-Hu-1) or the Delta (B.1.617.2) strain. Although all tested MSGs showed strong inhibitory activity against both strains, no correlations between MSG structural features and virus inhibition could be drawn. Nevertheless, the current study provides evidence for the maintenance of inhibitory activity of MSGs against evolving SARS-CoV-2 strains.
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DOI：
10.1016/j.jbc.2021.101207
发表时间：
2021-10
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Dwivedi R;Samanta P;Sharma P;Zhang F;Mishra SK;Kucheryavy P;Kim SB;Aderibigbe AO;Linhardt RJ;Tandon R;Doerksen RJ;Pomin VH
通讯作者：
Pomin VH
影响因子：
--
作者：
Goher SS;Ali F;Amin M
通讯作者：
Amin M
影响因子：
11.2
作者：
Chen, Shiguo;Xue, Changhu;Chai, Wengang
通讯作者：
Chai, Wengang
影响因子：
4.8
作者：
Farias, WRL;Valente, AP;Mourao, PAS
通讯作者：
Mourao, PAS
影响因子：
6.7
作者：
Mycroft-West, Courtney J.;Su, Dunhao;Skidmore, Mark A.
通讯作者：
Skidmore, Mark A.