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Carbohydrate-Binding Agents: Potential of Repurposing for COVID-19 Therapy.
Current Protein & Peptide Science ( IF 2.8 ) Pub Date : 2020-09-18 , DOI: 10.2174/1389203721666200918153717
Rajesh Kumar Gupta 1 , Girish R Apte 1 , Kiran Bharat Lokhande 2 , Satyendra Mishra 3 , Jayanta K Pal 1
Affiliation  

With the emergence of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the whole world is suffering from atypical pneumonia which resulted in more than 559,047 deaths worldwide. In this time of crisis and urgency, the only hope comes from new candidate vaccines and potential antivirals. However, formulating new vaccines and synthesizing new antivirals is a laborious task. Therefore, considering the high infection rate and mortality due to COVID-19, utilization of previous information, and repurposing of existing drugs against valid viral targets has emerged as a novel drug discovery approach in this challenging time. The transmembrane spike (S) glycoprotein of coronaviruses (CoVs) which facilitates virus entry into the host cells, exists as homotrimeric form and is covered with N-linked glycans. S glycoprotein is known as the main target of antibodies having neutralizing potency and is also considered as an attractive target for therapeutic or vaccine development. Similarly, targeting of N-linked glycans of S glycoprotein envelop of CoV via carbohydrate-binding agents (CBAs) could serve as an attractive therapeutic approach for developing novel antivirals. CBAs from natural sources like lectins from plants, marine algae and prokaryotes and lectin mimics like Pradimicin-A (PRM-A) have shown antiviral activities against CoV and other enveloped viruses. However, the potential use of CBAs specifically lectins was limited due to unfavorable responses like immunogenicity, mitogenicity, hemagglutination, inflammatory activity, cellular toxicity, etc. Here, we have reviewed the current scenario of CBAs as antivirals against CoVs, presented strategies to improve the efficacy of CBAs against CoVs; and studied the molecular interactions between CBAs (lectins and PRM-A) with Man9 by molecular docking for potential repurposing against CoVs in general and the SARS-CoV-2 in particular.

中文翻译:

碳水化合物结合剂:重新应用COVID-19疗法的潜力。

随着新型严重急性呼吸系统综合症冠状病毒2(SARS-CoV-2)的出现,整个世界都在遭受非典型肺炎的折磨,全世界范围内共有559,047例死亡。在危机和紧急时刻,唯一的希望来自新的候选疫苗和潜在的抗病毒药。但是,配制新疫苗和合成新抗病毒药是一项艰巨的任务。因此,考虑到由于COVID-19导致的高感染率和高死亡率,利用现有信息以及针对有效病毒靶点重新利用现有药物已成为在这一具有挑战性的时代出现的新型药物发现方法。冠状病毒(CoVs)的跨膜尖峰(S)糖蛋白,可促进病毒进入宿主细胞,以同源三聚体形式存在,并被N-连接的聚糖覆盖。S糖蛋白被称为具有中和力的抗体的主要靶标,并且也被认为是治疗或疫苗开发的有吸引力的靶标。同样,通过碳水化合物结合剂(CBA)靶向CoV的S糖蛋白包膜的N-连接聚糖可以作为开发新型抗病毒剂的有吸引力的治疗方法。天然来源的CBA(例如植物,海藻和原核生物的凝集素)和Pradimicin-A(PRM-A)等凝集素模拟物已显示出对CoV和其他包膜病毒的抗病毒活性。但是,由于诸如免疫原性,促有丝分裂性,血细胞凝集性,炎性活性,细胞毒性等不良反应,CBAs特异性凝集素的潜在用途受到限制。提出了提高CBA对抗CoV效力的策略;并通过分子对接研究了CBA(凝集素和PRM-A)与Man9之间的分子相互作用,以潜在地针对CoV,尤其是针对SARS-CoV-2。
更新日期:2020-09-18
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