Alsolami Ahmed, Dirar Amina I, Konozy Emadeldin Hassan E, Osman Makarim El-Fadil M, Ibrahim Mohanad A, Alshammari Khalid Farhan, Alshammari Fawwaz, Alazmi Meshari, Said Kamaleldin B
Department of Internal Medicine, College of Medicine, University of Ha'il, Ha'il 55476, Saudi Arabia.
Medicinal, Aromatic Plants and Traditional Medicine Research Institute (MAPTRI), National Center for Research, Mek Nimr Street, Khartoum 11111, Sudan.
Curr Issues Mol Biol. 2023 Jul 14;45(7):5879-5901. doi: 10.3390/cimb45070372.
Multidisciplinary research efforts on potential COVID-19 vaccine and therapeutic candidates have increased since the pandemic outbreak of SARS-CoV-2 in 2019. This search has become imperative due to the increasing emergences and limited widely available medicines. The presence of bioactive anti-SARS-CoV-2 molecules was examined from various plant sources. Among them is a group of proteins called lectins that can bind carbohydrate moieties. In this article, we present ten novel, chitin-specific Hevein-like lectins that were derived from v1.0's genome. The capacity of these lectin homologs to bind with the spike protein of SARS-CoV-2 was examined. Using the HDOCK server, 3D-modeled Hevein-domains were docked to the spike protein's receptor binding domain (RBD). The Smo446851, Smo125663, and Smo99732 interacted with Asn343-located complex -glycan and RBD residues, respectively, with binding free energies of -17.5, -13.0, and -26.5 Kcal/mol. The molecular dynamics simulation using Desmond and the normal-state analyses via torsional coordinate association for the Smo99732-RBD complex using iMODS is characterized by overall higher stability and minimum deformity than the other lectin complexes. The three lectins interacting with carbohydrates were docked against five individual mutations that frequently occur in major SARS-CoV-2 variants. These were in the spike protein's receptor-binding motif (RBM), while Smo125663 and Smo99732 only interacted with the spike glycoprotein in a protein-protein manner. The precursors for the Hevein-like homologs underwent additional characterization, and their expressional profile in different tissues was studied. These in silico findings offered potential lectin candidates targeting key -glycan sites crucial to the virus's virulence and infection.
自2019年严重急性呼吸综合征冠状病毒2（SARS-CoV-2）大流行爆发以来，针对潜在的COVID-19疫苗和治疗候选药物的多学科研究工作有所增加。由于新出现的病例不断增加且广泛可用的药物有限，这种探索变得势在必行。人们从各种植物来源中检测了具有生物活性的抗SARS-CoV-2分子。其中有一类称为凝集素的蛋白质，它们可以结合碳水化合物部分。在本文中，我们展示了十种新的、几丁质特异性的类橡胶素凝集素，它们来自v1.0基因组。研究了这些凝集素同源物与SARS-CoV-2刺突蛋白结合的能力。使用HDOCK服务器，将三维建模的橡胶素结构域对接至刺突蛋白的受体结合域（RBD）。Smo446851、Smo125663和Smo99732分别与位于Asn343的复合聚糖和RBD残基相互作用，结合自由能分别为-17.5、-13.0和-26.5千卡/摩尔。使用Desmond进行的分子动力学模拟以及通过iMODS对Smo99732-RBD复合物进行的基于扭转坐标关联的常态分析表明，与其他凝集素复合物相比，其总体稳定性更高，畸形程度最小。这三种与碳水化合物相互作用的凝集素针对主要SARS-CoV-2变体中经常出现的五个单独突变进行了对接。这些突变位于刺突蛋白的受体结合基序（RBM）中，而Smo125663和Smo99732仅以蛋白质-蛋白质的方式与刺突糖蛋白相互作用。对类橡胶素同源物的前体进行了进一步表征，并研究了它们在不同组织中的表达谱。这些计算机模拟结果提供了潜在的凝集素候选物，可靶向对病毒毒力和感染至关重要的关键聚糖位点。
