重组凝集素作为抗COVID-19的先锋抗病毒药物

Dr. Ashraf Abdullah Saad
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引用次数: 2

摘要

针对导致2019冠状病毒病(COVID-19)的致命严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)的疫苗设计和抗病毒治疗的主要目标是冠状病毒表面刺突(S)糖蛋白。与其他包膜病毒一样,S糖蛋白被宿主源性聚糖的致密糖“外衣”所掩盖,通过分子模仿介导免疫逃避,从而屏蔽宿主免疫应答的免疫原性表面蛋白。矛盾的是,同样的保护性聚糖屏蔽可以使这些糖包被病毒容易受到先天免疫系统可溶性凝集素的免疫攻击,而先天免疫系统仍然能够识别这些聚糖为病原体相关分子模式(PAMPs),从而导致补体激活。实际上,靶向病毒相关聚糖的重组凝集素有可能被用作抗病毒药物;因此,重组凝集素与病毒的结合可能代表了病毒感染治疗的范式转变。同样,SARS-CoV-2相关聚糖可以作为创新的抗sarscov -2药物,为重组凝集素提供新的靶点。不幸的是,目前的药理学障碍限制了重组凝集素进入临床试验,但对这些药物的潜在有用修饰进行更积极的研究,可以真正开发出基于抗病毒凝集素的治疗方法的新领域。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Recombinant lectins as pioneering anti-viral agents against COVID-19
The primary target for vaccine design and anti-viral therapeutics for the deadly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) is the coronavirus surface spike (S) glycoprotein. Like other enveloped viruses, S glycoproteins are masked by a dense sugar “coat” of host-derived glycans that mediate immune evasion by molecular mimicry through shielding the immunogenic surface proteins from host immune responses. Paradoxically, this same protective glycan shield can make these sugar-coated viruses vulnerable to immune attack by soluble lectins of the innate immune system that are still able to recognise these glycans as pathogen-associated molecular patterns (PAMPs) leading to complement activation. In reality, recombinant lectins that target virus-associated glycans have the potential to be used as anti-viral agents; and therefore, binding of recombinant lectins to viruses could represent a paradigm shift for viral infection therapy. Likewise, SARS-CoV-2- associated glycans can offer novel targets for recombinant lectins as innovative anti-SARSCoV-2 agents. Unfortunately, pharmacological hurdles currently constrain the entry of recombinant lectins into clinical trials but more vigorous research into potentially useful modifications of these agents can truly develop a new landscape of anti-viral lectin-based therapeutics.
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