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氧化锌-绿原酸纳米结构复合物抑制新冠病毒发病机制并提高羟氯喹疗效。

ZnO-chlorogenic acid nanostructured complex inhibits Covid-19 pathogenesis and increases hydroxychloroquine efficacy.

作者信息

Abomughaid Mosleh M, Nofal Mohammed S, Ghaleb Khaled I, Seadawy Mohamed G, AbdEl-Wahab Miral G, Hegazy Alaa S, Ghareeb Doaa A

机构信息

Medical Laboratory Sciences Department, College of Applied Medical Sciences, University of Bisha, Bisha, Saudi Arabia.

Center of Excellency for Drug Preclinical Studies (CE-DPS), Pharmaceutical and Fermentation Industries Development Centre, City of Scientific Research and Technological Applications (SRTA-City), New Borg El-Arab, Alexandria, Egypt.

出版信息

J King Saud Univ Sci. 2022 Nov;34(8):102296. doi: 10.1016/j.jksus.2022.102296. Epub 2022 Aug 30.

Abstract

OBJECTIVE

The study purpose was to compare the anti- novel coronavirus disease 2019 (COVID-19) property of chlorogenic acid (CGA) and Zinc oxide nanoparticles (ZnO-NP) with the new valid synthesized complex of ZnO /CGA-NPs.

METHODS

The facile mixing method was utilized to prepare ZnO/CGA-NPs. The effect of different ZnO/CGA-NPs concentrations on papain-like protease (PL) and spike protein- receptor-binding domain (RBD) was measured by ELISA technique. The compounds effects on SARS-CoV2 were determined on viral entry, replication, and assembly by using plaque reduction assay, qPCR, and ELISA techniques. Their individual effects or mixed with hydroxychloroquine (HCQ) on erythrocytes (RBCs) and leukocytes (WBCs) were evaluated by routine cell culture technique. Finally, turbidity and agar well diffusion assays were done to evaluate their antimicrobial properties against , , , and .

RESULTS

The results confirmed that the uniformly dispersed ZnO-NPs were converted to aggregated form of ZnO/CGA-NPs upon the addition of CGA. The inhibitory concentration 50 (IC) of ZnO /CGA-NPs against RBD, angiotensin-converting enzyme 2 (ACE2) and PL were 1647.7, 323.3 µg/mL and 38.7 µg/mL, respectively. Also, it inhibited E-gene, RdRp gene, E-protein, and spike protein with an IC of 0.11, 0.13, 0.48, and 0.37 µg/mL, respectively. It acted as an antimicrobial against all tested organisms with a minimum inhibitory concentration (MIC) of 26 µg/mL. Finally, ZnO/CGA-NPs Complex (0.1 IC) prevented the cytotoxic effect of HCQ on RBCs and WBC by 92.3 and 90 %, respectively.

CONCLUSION

ZnO/CGA-NPs Complex can be considered as a new anti- severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) compound.

摘要

目的

本研究旨在比较绿原酸(CGA)、氧化锌纳米颗粒(ZnO-NP)与新合成的有效复合物ZnO/CGA-NPs对2019年新型冠状病毒病(COVID-19)的抗病毒特性。

方法

采用简便混合法制备ZnO/CGA-NPs。通过酶联免疫吸附测定(ELISA)技术检测不同浓度的ZnO/CGA-NPs对木瓜样蛋白酶(PL)和刺突蛋白受体结合域(RBD)的影响。利用噬斑减少试验、定量聚合酶链反应(qPCR)和ELISA技术,测定这些化合物对严重急性呼吸综合征冠状病毒2(SARS-CoV2)在病毒进入、复制和组装方面的作用。通过常规细胞培养技术评估它们单独或与羟氯喹(HCQ)混合对红细胞(RBC)和白细胞(WBC)的影响。最后,进行浊度和琼脂孔扩散试验,以评估它们对金黄色葡萄球菌、大肠杆菌、铜绿假单胞菌和白色念珠菌的抗菌性能。

结果

结果证实,加入CGA后,均匀分散的ZnO-NPs转变为ZnO/CGA-NPs的聚集形式。ZnO/CGA-NPs对RBD、血管紧张素转换酶2(ACE2)和PL的半数抑制浓度(IC50)分别为1647.7、323.3 μg/mL和38.7 μg/mL。此外,它对E基因、RNA依赖性RNA聚合酶(RdRp)基因、E蛋白和刺突蛋白的IC50分别为0.11、0.13、0.48和0.37 μg/mL。它对所有测试微生物均有抗菌作用,最低抑菌浓度(MIC)为26 μg/mL。最后,ZnO/CGA-NPs复合物(0.1 IC50)分别使HCQ对RBC和WBC的细胞毒性作用降低了92.3%和90%。

结论

ZnO/CGA-NPs复合物可被视为一种新型抗SARS-CoV2化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/9425706/1e8a72cb58da/gr1_lrg.jpg

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