Chemical and spectroscopic characterization of (Artemisinin/Querctin/ Zinc) novel mixed ligand complex with assessment of its potent high antiviral activity against SARS-CoV-2 and antioxidant capacity against toxicity induced by acrylamide in male rats
Samy M El-Megharbel, Safa H Qahl, Bander Albogami, Reham Z Hamza
PeerJ, doi:10.7717/peerj.15638
A novel Artemisinin/Quercetin/Zinc (Art/Q/Zn) mixed ligand complex was synthesized, tested for its antiviral activity against coronavirus (SARS-CoV-2), and investigated for its effect against toxicity and oxidative stress induced by acrylamide (Acy), which develops upon cooking starchy foods at high temperatures. The synthesized complex was chemically characterized by performing elemental analysis, conductance measurements, FT-IR, UV, magnetic measurements, and XRD. The morphological surface of the complex Art/Q/Zn was investigated using scanning and transmission electron microscopy (SEM and TEM) and energy dispersive X-ray analysis (XRD). The in vitro antiviral activity of the complex Art/Q/Zn against SARS-CoV-2 and its in vivo activity against Acy-induced toxicity in hepatic and pulmonary tissues were analyzed. An experimental model was used to evaluate the beneficial effects of the novel Art/Q/Zn novel complex on lung and liver toxicities of Acy. Forty male rats were randomly divided into four groups: control, Acy (500 mg/Kg), Art/Q/Zn (30 mg/kg), and a combination of Acy and Art/Q/Zn. The complex was orally administered for 30 days. Hepatic function and inflammation marker (CRP), tumor necrosis factor, interleukin-6 (IL-6), antioxidant enzyme (CAT, SOD, and GPx), marker of oxidative stress (MDA), and blood pressure levels were investigated. Histological and ultrastructure alterations and caspase-3 variations (immunological marker) were also investigated. FT-IR spectra revealed that Zn (II) is able to chelate through C=O and C-OH (Ring II) which are the carbonyl oxygen atoms of the quercetin ligand and carbonyl oxygen atom C=O of the Art ligand, forming Art/Q/Zn complex with the chemical formula The novel complex exhibited a potent anti-SARS-CoV-2 activity even at a low concentration (IC 50 = 10.14 µg/ml) and was not cytotoxic to the cellular host (CC 50 = 208.5 µg/ml). Art/Q/Zn may inhibit the viral replication and binding to the angiotensin-converting enzyme-2 (ACE2) receptor and the main How to cite this article El-Megharbel SM, Qahl SH, Albogami B, Hamza RZ. 2024. Chemical and spectroscopic characterization of (Artemisinin/Querctin/ Zinc) novel mixed ligand complex with assessment of its potent high antiviral activity against SARS-CoV-2 and antioxidant capacity against toxicity induced by acrylamide in male rats. PeerJ 12:e15638 http://doi.org/10.7717/peerj.15638 protease inhibitor (M Pro ), thereby inhibiting the activity of SARS-CoV-2 and this proved by the molecular dynamics simulation. It alleviated Acy hepatic and pulmonary toxicity by improving all biochemical markers. Therefore, it can be concluded that the novel formula Art/Q/Zn complex is an effective antioxidant agent against the oxidative stress series, and it has high inhibitory effect against SARS-CoV-2.
ADDITIONAL INFORMATION AND DECLARATIONS Funding The researchers were funded by the Deanship of Scientific Research, Taif University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Grant Disclosures The following grant information was disclosed by the authors: The Deanship of Scientific Research, Taif University.
Competing Interests The authors declare there are no competing interests.
Author Contributions • Samy M. El-Megharbel conceived and designed the experiments, performed the experiments, analyzed the data, prepared figures and/or tables, authored or reviewed drafts of the article, and approved the final draft. • Safa H. Qahl conceived and designed the experiments, performed the experiments, analyzed the data, prepared figures and/or tables, authored or reviewed drafts of the article, and approved the final draft. • Bander Albogami conceived and designed the experiments, performed the experiments, analyzed the data, prepared figures and/or tables, authored or reviewed drafts of the article, and approved the final draft. • Reham Z. Hamza conceived and designed the experiments, performed the experiments, analyzed the data, prepared figures and/or tables, authored or reviewed drafts of the article, and approved the final draft.
Animal Ethics The following information was supplied relating to ethical approvals (i.e., approving body and any reference numbers): The Zagazig University ethical..
References
Abo, None
Abubakar, Ukwuani, Mande, Antihypertensive activity of Hibiscus Sabdariffa aqueous calyx extract in Albino rats, Sky Journal of Biochemistry Research
Aebi, Catalase in vitro, Methods in Enzymology
Al-Thubaiti, El-Megharbel, Albogami, Hamza, Synthesis, spectroscopic, chemical characterizations, anticancer capacities against HepG-2, antibacterial and antioxidant activities of cefotaxime metal complexes with Ca (II), Cr (III), Zn (II), Cu (II) and Se (IV), Antibiotics,
doi:10.3390/antibiotics11070967Anand, Ziebuhr, Wadhwani, Mesters, Hilgenfeld, Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs, Science
Augustin, Staines, Kamarulzaman, Platteeuw, Artesunate may attenuate the effects of cytokine release syndrome (CRS) in Covid-19 disease by targeting Interleukin-6 and associated inflammatory response pathways, OSF Preprints,
doi:10.31219/osf.io/qgkcvBabcock, Esshaki, Thomas, Ambrosino, Amino acids 270 to 510 of the severe acute respiratory syndrome coronavirus spike protein are required for interaction with receptor, Journal of Virology
Badraoui, Saoudi, Hamadou, Elkahoui, Siddiqui et al., Antivirial effects of Artemisinin and it's derivatives against SARS-CoV-2 main proteases: computational evidences and interactions with ACE2 allelic variants, Pharmaceuticals,
doi:10.3390/ph15020129Bellamy, The infrared spectra of complex molecules
Charisiadis, Kontogianni, Tsiafoulis, Tzakos, Siskos et al., None
Daina, Michielin, Zoete, SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules, Nucleic Acids Research,
doi:10.1093/nar/gkz382Dean, Sullivan, Soe, OpenEpi: open-source epidemiologic statistics for public health
Dhawan, Priyanka, Op, Omicron SARS-CoV-2 variant: reasons of emergence and lessons learnt, International Journal of Surgery,
doi:10.1016/j.ijsu.2021.106198Dimitrov, The secret life of ACE2 as a receptor for the SARS virus, Cell
Efferh, Beyond malaria: the inhibition of viruses by artemisinin-type compounds, Biotechnology Advances
El-Megharbel, 41/47 hydrogen bonds of phenol-containing natural products and model compounds, Molecules
El-Megharbel, Alsawat, Al-Salmi, Hamza, Utilizing of (Zinc Oxide nano-spray) for disinfection against SARS-CoV-2' and testing its biological effectiveness on some biochemical parameters during (COVID-19 Pandemic) ZnO nanoparticles have antiviral activity against (SARS-CoV-2), Coatings,
doi:10.3390/coatings11040388El-Megharbel, Hamza, Synthesis, spectroscopic characterizations, conductometric titration and investigation of potent antioxidant activities of gallic acid complexes with Ca (II), Cu (II), Zn(III), Cr(III) and Se (IV) metal ions, Journal of Molecular Liquids,
doi:10.1016/j.molliq.2022.119196El-Megharbel, None, PeerJ
Elkhodary, Treatment of COVID-19 by controlling the activity of the nuclear factor-Kappa B, Cell Biology
Elmaaty, Eldehna, Khattab, Kutkat, Alnajjar et al., Anticoagulants as potential SARS-CoV-2 M pro inhibitors for COVID-19 patients: in vitro, molecular docking, molecular dynamics, DFT, and SAR studies, International Journal of Molecular Sciences,
doi:10.3390/ijms232012235Erdemli, Erdemli, Turkoz, Gul, Yigitcan et al., The effects of acrylamide and Vitamin E administration during pregnancy on adult rats' testis, Andrologia
Fa, El-Megharbel, Hamza, Synthesis and spectroscopic study of novel mixed ligand formula Artemisinin/Zn and assessment of its inhibitory effect against SARS-CoV-2, Heliyon
Gedik, Erdemli, Gul, Yigitcan, Bag et al., Hepatoprotective effects of crocin on biochemical and histopathological alterations following acrylamide-induced liver injury in Wistar rats, Biomedicine and Pharmacotherapy,
doi:10.1016/j.biopha.2017.08.139Gendrot, Duflot, Boxberger, Delandre, Jardot et al., Antimalarial artemisinin-based combination therapies (ACT) and COVID-19 in Africa: in vitro inhibition of SARS-CoV-2 replication by mefloquine-artesunate, International Journal of Infectious Diseases,
doi:10.1016/j.ijid.2020.08.032Hamza, Alaryani, Alotaibi, Al-Harthi, Alotaibi et al., Efficacy of Prednisolone/Zn metal complex and artemisinin either alone or in combination on lung functions after excessive exposure to electronic cigarettes aerosol with assessment of antibacterial activity, Crystals,
doi:10.3390/cryst12070972Hamza, Eh, Omar, The antioxidant activity of quercetin and its effect on acrylamide hepatotoxicity in liver of rats, Latin American Journal of Pharmacy
Hamza, Gobouri, Al-Yasi, Ta, Sm, New sterilization strategy using TiO 2 nanotubes for production of free radicals that eliminate viruses and application of a treatment strategy to combat infections caused by emerging SARS-CoV-2 during the COVID-19 pandemic, Coatings,
doi:10.3390/coatings11060680Hamza, Se, Malik, Protective and antioxidant role of selenium nanoparticles and vitamin c against acrylamide induced hepatotoxicity in male mice, International Journal of Pharmacology,
doi:10.3923/ijp.2019.664.674Hoffmann, Kleine-Weber, Schroeder, Krüger, Herrler et al., SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor, Cell,
doi:10.1016/j.cell.2020.02.052Iftekhar, Rahman, Monyck, Carl, Ulh, Artemisia annua L. and its derivatives: their antiviral effects on COVID-19 and possible mechanisms, Journal of Exploratory Research in Pharmacology
Iyengar, Study of crude drugs. 2nd edition, Manipal: College of Pharmaceutical Sciences
Joshi, Joshi, Sharma, Mathpal, Pundir et al., In silico screening of natural compounds against COVID-19 by targeting Mpro and ACE2 using molecular docking, European Review for Medical and Pharmacological Sciences
Kalalagh, Kashkooli, Babaei, Rezaei, Der Krol Ar, Artemisinins in combating viral infections like SARS-CoV-2, inflammation and cancers and options to meet increased global demand, Frontiers in Plant Science
Kapepula, Kabengele, Kingombe, Van Bambeke, Tulkens et al., Artemisia spp. derivatives for COVID-19 treatment: anecdotal use, political hype, treatment potential, challenges, and road map to randomized clinical trials, American Journal of Tropical Medicine and Hygiene
Kaptein, Efferth, Leis, Rechter, Auerochs et al., The anti-malaria drug artesunate inhibits replication of cytomegalovirus in vitro and in vivo, Antiviral Research
Karamoddini, Emami, Ghannad, Sani, Sahebkar, Antiviral activities of aerial subsets of Artemisia species against Herpes Simplex virus type 1 (HSV1) in vitro, Asian Biomedicine
Kerim, Recep, Aydin, Tuba, Emine, Evaluation of the protective effects of morin against acrylamide-induced lung toxicity by biomarkers of oxidative stress, inflammation, apoptosis, and autophagy, Journal of Food Biochemistry,
doi:10.1111/jfbc.14111Krishna, Ganapathi, Ster, Saeed, Cowan et al., Randomized, double blind, placebo-controlled pilot study of oral artesunate therapy for colorectal cancer, EbioMedicine
Lassi, Moin, Bhutta, Zinc supplementation for the prevention of pneumonia in children aged 2 months to 59 months, Cochrane Database of Systematic Reviews,
doi:10.1002/14651858.CD005978.pub3Lever, Inorganic electronic spectroscopy
Maret, Zinc in pancreatic islet biology, insulin sensitivity, and diabetes, Preventive Nutrition and Food Science
Mohammad, Prakash, Ranjan, Manjeet, Azaj et al., Structural investigations, Hirsfeld surface analyses, and molecular docking studies of a phenoxo-bridged binuclear Zinc(II) complex, Journal of Molecular Structure,
doi:10.1016/j.molstruc.2021.132039Mohammad, Saikh, Mahboob, Agata, Rafal et al., Design, structural investigations and antimicrobial activity of pyrazole nucleating copper and zinc complexes, Polyhedron. Polyhedron,
doi:10.1016/j.poly.2020.114991Mohapatra, Kandi, Sarangi, Verma, Tuli et al., a. The recently emerged BA.4 and BA.5 lineages of omicron and their global health concerns amid the ongoing wave of COVID-19 pandemic -correspondence, International Journal of Surgery,
doi:10.1016/j.ijsu.2022.106698Mohapatra, Kandi, Verma, Dhama, Challenges of the omicron (B.1.1.529) variant and its lineages: a global perspective, ChemBioChem,
doi:10.1002/cbic.202200059Mohapatra, Mahal, Kutikuppala, Pal, Kandi et al., Renewed global threat by the novel SARS-CoV-2 variants, Frontiers in Virology,
doi:10.3389/fviro.2022.1077155Mohapatra, Mohammad, Pranabk, Mohnad, Lina et al., Computational studies on potential new anti-Covid-19 agents with a multitarget mode of action, Journal of King Saud University -Science,
doi:10.1016/j.jksus.2022.102086Mohnad, Mohapatra, Ashish, Pranab, Eltayb et al., In silico studies on phytochemicals to combat the emerging COVID-19 infection, Journal of Saudi Chemical Society,
doi:10.1016/j.jscs.2021.101367Nakamoto, Infrared and Raman spectra of inorganic and coordination compounds
Nakamoto, Infrared spectra of inorganic and coordination compounds
Nasr, Badraoui, Approach of utilizing Artemisia herbs to treat COVID-19, Brazilian Journal of Pharmaceutical Sciences
Ohkawa, Ohishi, Yagi, Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction, Analytical Biochemistry
Olechnowicz, Tinkov, Skalny, Zinc status is associated with inflammation, oxidative stress, lipid, and glucose metabolism, The Journal of Physiological Sciences
Paglia, Valentive, Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase, Journal of Laboratory Clinical Medicine
Perlman, Netland, Coronaviruses post-SARS: update on replication and pathogenesis, Nature Reviews
Pimpin, Cortez-Pinto, Negro, Corbould, Lazarus et al., EASL HEPAHEALTH steering committee. Burden of liver disease in Europe: epidemiology and analysis of risk factors to identify prevention policies, Journal of Hepatology
Rajan, Deeksha, Premprakash, Bhanu, Vikas et al., Phytocompounds of Rheum emodi, Thymus serpyllum, and Artemisia annua inhibit spike protein of SARS-CoV-2 binding to ACE2 receptor: in silico approach, Current Pharmacology Reports
Ranjan, Satwik, Tarun, Venkataramana, Ajit et al., SARS-CoV-2 and its variants of concern including Omicron: a never ending pandemic, Chemical Biology and Drug Design
Rasheed, Efferth, Asangani, Allgayer, First evidence that antimalarial drug artesunate inhibits invasion and in-vivo metastasis in lung cancer by targeting essential extracellular proteases, International Journal of Cancer
Refat, Hamza, Adam, Saad, Gobouri et al., Quercetin/Zinc complex and stem cells: a new drug therapy to ameliorate glycometabolic control and pulmonary dysfunction El-Megharbel et al, PLOS ONE,
doi:10.1371/journal.pone.0246265Rk, Ranjan, Manjeet, Mohammad, Hardeep et al., Synthesis, structural investigations, XRD, DFT, anticancer and molecular docking study of a series of thiazolebased Schiff base metal complexes, Journal of Molecular Structure,
doi:10.1016/j.molstruc.2022.134676Rolta, Salaria, Kumar, Sourirajan, Dev, Phytocompounds of Rheum emodi, Thymus serpyllum and Artemisia annua inhibit COVID-19 binding to ACE2 receptor in silico approach, Current Pharmacology Reports
Sanna, Ugone, Fadda, Micera, Garribba, Behavior of the potential antitumor V(IV)O complexes formed by flavonoid ligands. 3. Antioxidant properties and radical production capability, Journal of Inorganic Biochemistry
Sarin, Kumar, Eslam, George, Al-Mahtab et al., Liver diseases in the Asia-Pacifc region: a lancet gastroenterology & hepatology commission, The Lancet Gastroenterology and Hepatology
Scaccabarozzi, Signorini, Perego, Ilboudo, Ferrante, The use of antimalarial drugs against viral infection, Microorganisms
Shereen, Khan, Kazmi, Bashir, Siddique, COVID-19 infection: origin, transmission, and characteristics of human coronaviruses, Journal of Advanced Research
Sun, Oberley, Li, Simple method for clinical assay of superoxide dismutase, Clinical Chemistry
Ulrich, Pillat, CD147 as a target for COVID-19 treatment: suggested effects of azithromycin and stem cell engagement, Stem Cell Reviews and Reports
Ulrich, Pillat, a. CD147 as a target for COVID-19 treatment: suggested effects of azithromycin and stem cell engagement, Stem Cell Reviews and Reports
Vessal, Hemmati, Vasei, Antidiabetic effects of quercetin in streptozotocininduced diabetic rats, Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology
Wang, Chen, Zhang, Deng, Lian et al., CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells, Signal Transduction and Targeted Therapy,
doi:10.1038/s41392-020-00426-xWang, Fan, Zhang, Gao, Wang, The global burden of liver disease: the major impact of China, Hepatology
Wong, Li, Moore, Choe, Farzan, 193-amino acid fragment of the SARS coronavirus S protein efficiently binds angiotensin-converting enzyme 2, International Journal of Biological and Chemical Sciences
Xiao, Chakraborti, Dimitrov, Gramatikoff, Dimitrov, The SARS-CoV S glycoprotein: expression and functional characterization, Biochemical and Biophysical Research Communications
Xinyu, Huijun, Xiaozhen, Hongliang, Spike protein mediated membrane fusion during SARS-CoV-2 infection, Journal of Medical Virology
Ye, Jianrong, Anti-malarial drug: the emerging role of artemisinin and its derivatives in liver disease treatment, Chinese Medicine,
doi:10.1186/s13020-021-00489-0Zarezade, Moludi, Mostafazadeh, Mohammadi, Veisi, Antioxidant and hepatoprotective effects of Artemisia dracunculus against CCl4-induced hepatotoxicity in rats, Avicenna Journal of Phytomedicine
Zeynep, Erman, Harika, Eyup, Effects of acrylamide and crocin on rat lung tissue, Annals of Medical Research
Şevki, Volkan, Iqra, Azhar, Ameer et al., Caffeic acid derivatives (CAFDs) as inhibitors of SARS-CoV-2: CAFDs-based functional foods as a potential alternative approach to combat COVID-19, Phytomedicine,
doi:10.1016/j.phymed.2020.153310
