학술논문
Nanoparticles of ZnO/Berberine complex contract COVID-19 and respiratory co-bacterial infection in addition to elimination of hydroxychloroquine toxicity
Document Type
Article
Author
Ghareeb Doaa A.; Saleh Samar R.; Seadawy Mohamed G.; Nofal Mohammed S.; Abdulmalek Shaymaa A.; Hassan Salma. F.; Khedr Shaimaa M.; AbdElwahab Miral G.; Sobhy Ahmed A.; Abdel-Hamid Ali saber Ali; Yassin Abdelrahman Mohamed; Elmoneam Alshimaa A. Abd; Masoud Aliaa A.; Kaddah Mohamed M. Y.; El-Zahaby Sally A.; Al-mahallawi Abdulaziz Mohsen; El-Gharbawy Alaa M.; Zaki Ahmed; Seif Inas K.; Kenawy Marwa Y.; Amin Magdy; Amer Khaled; El Demellawy Maha Adel
Source
Journal of Pharmaceutical Investigation, 51(6), pp.735-757 Nov, 2021
Subject
Language
English
ISSN
2093-6214
2093-5552
2093-5552
Abstract
Purpose A novel coronavirus (COVID-19) that has not been previously identified in humans and has no specific treatment has recently spread. Treatment trials using antiviral and immune-modulating drugs such as hydroxychloroquine (HCQ) were used to control this viral outbreak however several side effects have emerged. Berberine (BER) is an alkaloid that has been reported to reveal some pharmacological properties including antioxidant and antimicrobial activities. Additionally, Zinc oxide nanoparticles (ZnO-NPs) possess potent antioxidant and anti-inflammatory properties. Therefore, this study was undertaken to estimate the efficiency of both BER and synthetic ZnO/BER complex as an anti-COVID-19 therapy. Methods First, the ZnO/BER complex was prepared by the facile mixing method. Then in vitro studies on the two compounds were conducted including VeroE6 toxicity, anti-COVID-19 activity, determination of inhibitory activity towards papain-like proteinase (PL pro) and spike protein- and receptor- binding domain (RBD) as well as assessment of drug toxicity on RBCs. Results The results showed that ZnO/BER complex acts as an anti-COVID-19 by inhibiting spike protein binding with angiotensin-converting enzyme II (ACE II), PL pro activity, spike protein and E protein levels, and expression of both E-gene and RNA dependent RNA polymerase (RdRp) at a concentration lower than that of BER or ZnO-NPs alone. Furthermore, ZnO/BER complex had antioxidant and antimicrobial properties where it prevents the auto oxidation of 2,2-Diphenyl- 1-picrylhydrazyl (DPPH) and the culture of lower respiratory system bacteria that affected Covid 19 patients. The ZnO/BER complex prevented as well the HCQ cytotoxic effect on both RBC and WBC (in vitro) and hepatotoxicity, nephrotoxicity and anemia that occurred after HCQ long administration in vivo. Conclusion The ZnO/BER complex can be accounted as promising anti-COVID 19 candidate because it inhibited the virus entry, replication, and assembly. Furthermore, it could be used to treat a second bacterial infection that took place in hospitalized COVID 19 patients. Moreover, ZnO/BER complex was found to eliminate the toxicity of long-term administration of HCQ in vivo.