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(L.) 林(Lam),药物研发的前沿,应对寨卡病毒和微生物感染-体外和计算视角。

(L.) Lam. at the Forefront of Pharma to Confront Zika Virus and Microbial Infections-An In Vitro and In Silico Perspective.

机构信息

Department of Health Sciences, Faculty of Medicine and Health Sciences, University of Mauritius, Réduit 80837, Mauritius.

Unité Mixte Processus Infectieux en Milieu Insulaire Tropical, Plateforme Technologique CYROI, Université de la Réunion, INSERM U1187, CNRS UMR 9192, IRD UMR 249, 94791 Sainte Clotilde, La Réunion, France.

出版信息

Molecules. 2021 Sep 23;26(19):5768. doi: 10.3390/molecules26195768.

Abstract

The recent emergence of Zika virus (ZIKV) in Brazil and the increasing resistance developed by pathogenic bacteria to nearly all existing antibiotics should be taken as a wakeup call for the international authority as this represents a risk for global public health. The lack of antiviral drugs and effective antibiotics on the market triggers the need to search for safe therapeutics from medicinal plants to fight viral and microbial infections. In the present study, we investigated whether a mangrove plant, (L.) Lam. () collected in Mauritius, possesses antimicrobial and antibiotic potentiating abilities and exerts anti-ZIKV activity at non-cytotoxic doses. Microorganisms ATCC 25922, ATCC 27853, ATCC 70603, methicillin-resistant ATCC 43300 (MRSA), ATCC 13076, ATCC 9341, ATCC 25933, ATCC 11778 and ATCC 26555 were used to evaluate the antimicrobial properties. Ciprofloxacin, chloramphenicol and streptomycin antibiotics were used for assessing antibiotic potentiating activity. ZIKV (ZIKV) was used for assessing anti-ZIKV activity. In silico docking (Autodock 4) and ADME (SwissADME) analyses were performed on collected data. Antimicrobial results revealed that twig ethyl acetate (BTE) was the most potent extract inhibiting the growth of all nine microbes tested, with minimum inhibitory concentrations ranging from 0.19-0.39 mg/mL. BTE showed partial synergy effects against MRSA and when applied in combination with streptomycin and ciprofloxacin, respectively. By using a recombinant ZIKV-expressing reporter GFP protein, we identified both root aqueous and fruit aqueous extracts as potent inhibitors of ZIKV infection in human epithelial A549 cells. The mechanisms by which such extracts prevented ZIKV infection are linked to the inability of the virus to bind to the host cell surface. In silico docking showed that ZIKV E protein, which is involved in cell receptor binding, could be a target for cryptochlorogenic acid, a chemical compound identified in . From ADME results, cryptochlorogenic acid is predicted to be not orally bioavailable because it is too polar. Scientific data collected in this present work can open a new avenue for the development of potential inhibitors from to fight ZIKV and microbial infections in the future.

摘要

寨卡病毒(ZIKV)最近在巴西出现,致病性细菌对几乎所有现有抗生素的耐药性不断增强,这应该引起国际社会的警惕,因为这对全球公共卫生构成了威胁。市场上缺乏抗病毒药物和有效的抗生素,这促使人们需要从药用植物中寻找安全的治疗方法来对抗病毒和微生物感染。在本研究中,我们研究了从毛里求斯采集的一种红树林植物()是否具有抗菌和抗生素增效作用,并在非细胞毒性剂量下发挥抗 ZIKV 活性。使用微生物 ATCC 25922、ATCC 27853、ATCC 70603、耐甲氧西林金黄色葡萄球菌(MRSA)ATCC 43300、ATCC 13076、ATCC 9341、ATCC 25933、ATCC 11778 和 ATCC 26555 来评估抗菌性能。使用环丙沙星、氯霉素和链霉素抗生素来评估抗生素增效活性。使用 ZIKV(ZIKV)来评估抗 ZIKV 活性。对收集的数据进行了计算机对接(Autodock 4)和 ADME(SwissADME)分析。抗菌结果表明,树枝乙酸乙酯(BTE)是最有效的提取物,抑制了所有 9 种微生物的生长,最小抑菌浓度范围为 0.19-0.39mg/mL。BTE 对 MRSA 和 显示出部分协同作用,当分别与链霉素和环丙沙星联合使用时。通过使用表达重组 ZIKV 的 GFP 蛋白报告器,我们确定了根水提物和果水提物均为有效抑制人上皮 A549 细胞中 ZIKV 感染的抑制剂。这些提取物阻止 ZIKV 感染的机制与病毒无法与宿主细胞表面结合有关。计算机对接表明,参与细胞受体结合的 ZIKV E 蛋白可能是隐绿原酸的一个靶点,隐绿原酸是在 中发现的一种化合物。根据 ADME 结果,隐绿原酸由于极性太大,预计不能口服生物利用。本研究收集的科学数据为未来从 中开发潜在的 ZIKV 和微生物抑制剂开辟了新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6af/8510246/5ae2488346b0/molecules-26-05768-g001.jpg

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