不同來(lái)源的凝集素已被證明可通過(guò)抑制病毒病原體的感染從而顯示出強(qiáng)大的抗病毒特性。凝集素抗病毒活性在很大程度上是由于其可以與病毒包膜聚糖(envelope glycans)直接結(jié)合而阻止病毒進(jìn)入細(xì)胞。特別是對(duì)甘露糖和N-乙酰氨基葡萄糖(GlcNAc)糖基有親和力的植物凝集素,已被確定為預(yù)防人類免疫缺陷病毒(HIV)和冠狀病毒(SARS-CoV和MERS-CoV)病毒傳播的潛在治療藥物。
冠狀病毒是有包膜的單鏈RNA病毒,其至少含有四種結(jié)構(gòu)蛋白:膜蛋白(M)、包膜蛋白(E)、刺突蛋白(S)和核衣殼蛋白(N)。高度糖基化的病毒S蛋白介導(dǎo)病毒與細(xì)胞間的結(jié)合和融合。甘露糖結(jié)合凝集素通過(guò)S蛋白與高甘露糖型SARS-CoV N-聚糖結(jié)合,干擾冠狀病毒的進(jìn)入,阻止病毒附著于宿主細(xì)胞上。?
冠狀病毒S蛋白上的N-聚糖可能引起下游的抗病毒先天免疫應(yīng)答的激活。N-連接糖基化在甘露糖結(jié)合凝集素與SARS-CoV S蛋白的特異性相互作用中扮演重要角色。這種相互作用也會(huì)抑制冠狀病毒的受體結(jié)合。?
Vector是有許多植物凝集素產(chǎn)品的老牌制造商,已有文獻(xiàn)證實(shí),這些植物凝集素可以作為闡明抑制病毒活性方面的重要工具。以下是甘露糖特異性和甘露糖/葡萄糖特異性凝集素的列表。
??Galanthus nivalis
??Hippeastrum hybrid
??Narcissus pseudonarcissus
??Concanavalin A
??Lens culinaris
??Musa paradisiaca
??Pisum sativum
基于之前對(duì)冠狀病毒(如SARS-CoV和MERS-CoV)的研究,甘露糖特異性植物凝集素可用于研究引起COVID-19的新型冠狀病毒(SARS-CoV-2)的抗病毒特性。
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凝集素對(duì)受體結(jié)合和病毒融合的影響
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上圖為植物凝集素GNL和HHL在MHV-EFLM病毒感染LR7細(xì)胞過(guò)程中不同階段的抗病毒活性,實(shí)驗(yàn)采用熒光素酶測(cè)定法進(jìn)行評(píng)估。
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用于冠狀病毒研究的凝集素
產(chǎn)品 | 貨號(hào) | 規(guī)格 |
Galanthus Nivalis Lectin (GNL) |
Unconjugated | L-1240 | 5 mg |
Fluorescein Labeled | FL-1241 | 2?mg |
Agarose Bound (3 mg lectin/ml gel) | AL-1243 | 2 ml, 5 ml |
Biotin Labeled | B-1245 | 2 mg |
Hippeastrum Hybrid (Amaryllis) Lectin (HHL, AL) |
Unconjugated | L-1380 | 5 mg |
Biotin Labeled | B-1385 | 2 mg |
Narcissus Pseudonarcissus (Daffodil) Lectin (NPL, NPA, DL) |
Unconjugated | L-1370 | 5 mg |
Biotin Labeled | B-1375 | 2 mg |
Concanavalin A (Con A) |
Unconjugated | L-1000 | 500 mg |
Fluorescein Labeled | FL-1001 | 25 mg |
Rhodamine Labeled | RL-1002 | 25 mg |
Agarose Bound (6 mg lectin/ml gel) | AL-1003 | 10 ml, 100 ml |
Biotin Labeled | B-1005 | 5 mg |
Lens Culinaris Agglutinin (LCA, LcH) |
Unconjugated | L-1040 | 10 mg, 25 mg |
Fluorescein Labeled | FL-1041 | 5 mg |
DyLight 649 Labeled | DL-1048 | 1 mg |
Rhodamine Labeled | RL-1042 | 5 mg |
Agarose Bound (3 mg lectin/ml gel) | AL-1043 | 10 ml |
Biotin Labeled | B-1045 | 5 mg |
Musa Paradisiaca Lectin (BanLec) |
Unconjugated | L-1410 | 5 mg |
Pisum Sativum Agglutinin (PSA) |
Unconjugated | L-1050 | 10 mg |
Biotin Labeled | B-1055 | 5 mg |
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參考文獻(xiàn)
1. Mitchell, C. et al. Antiviral Lectins: Selective Inhibitors of Viral Entry. Antiviral Res. 2017 Jun; 142: 37–54. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414728/)
2. Keyaerts, E. et al. Plant lectins are potent inhibitors of coronaviruses by interfering with two targets in the viral replication cycle. Antiviral Res. 2007 Sep;75(3):179-87.?(https://www.sciencedirect.com/science/article/pii/S0166354207002380?via%3Dihub)
3. Ritchie, G., et al. Identification of N-linked carbohydrates from severe acute respiratory syndrome (SARS) spike glycoprotein. Virology. 2010 Apr 10;399(2):257-69. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412594/)
4. Fung, S. and Liu, DX. Post-translational modifications of coronavirus proteins: roles and function. Future Virol. (2018) 13(6), 405–430. (https://www.futuremedicine.com/doi/full/10.2217/fvl-2018-0008)
5. F. J. U. M. van der Meer, et al. The carbohydrate-binding plant lectins and the non-peptidic antibiotic pradimicin A target the glycans of the coronavirus envelope?glycoproteins. J Antimicrob Chemother. 2007 Oct; 60(4): 741–749. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110056/)
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