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. 2023 Jun;9(6):e17177.
doi: 10.1016/j.heliyon.2023.e17177. Epub 2023 Jun 19.

Synthesis and spectroscopic study of novel mixed ligand formula "Artemisinin/Zn" and assessment of its inhibitory effect against "SARS-CoV-2″

Fawziah A Al-Salmi  1 , Samy M El-Megharbel  2   3 , Reham Z Hamza  1   4
Affiliations

Synthesis and spectroscopic study of novel mixed ligand formula "Artemisinin/Zn" and assessment of its inhibitory effect against "SARS-CoV-2″

Fawziah A Al-Salmi et al. Heliyon. 2023 Jun.

Abstract

Background: Herein, a newly synthesised mixed ligand artemisinin/zinc (Art/Zn) is chemically characterised and examined against SARS-CoV-2.

Methods: The synthesised complex was thoroughly characterised using various spectroscopic methods (FT-IR, UV and XRD). Its surface morphology and chemical purity were investigated using transmission electron microscopy (TEM), scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX) analysis. The synthesised Art/Zn complex was tested for its inhibitory effects against SARS-CoV-2 using inhibitory concentration 50 (IC50) and cytotoxicity concentration 50 (CC50).

Results: The results reveal that the Art/Zn complex exhibits a moderate in vitro inhibitory effects against SARS-CoV-2, with a CC50 index of 213.6 μg/ml and an IC50 index of 66.79 μg/ml. Notably, it exhibits the inhibitory effect (IC50 = 66.79 μg/ml) at a very low concentration without any observable cytotoxic effects on host cells (CC50 = 213.6 μg/ml). Its mode of action against SARS-CoV-2 involves inhibiting the viral replication. The predicted target classes that Art/Zn may affect include kinases, which can regulate and inhibit the viral replication and binding to the angiotensin-converting enzyme-2 (ACE2) receptor and the main protease inhibitor (MPro), thereby inhibiting the activity of SARS-CoV-2 and proved by the molecular dynamics simulation.

Conclusion: We recommend using the Art/Zn complex owing to its moderate inhibitory and antiviral effects against the SARS-CoV-2 with a low cytotoxic effect on host (Vero E6) cells. We suggest conducting further prospective studies to investigate the biological effects of Art/Zn in animal models at different concentrations for testing its clinical efficacy and safety in inhibiting SARS-CoV-2 activities.

Keywords: Antiviral activity; Artemisinin; Cytotoxicity; SARS-CoV-2; Zinc metal.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
Chemical structure of Art.
Fig 2
Fig 2
Synthesis of Artemisinin/zinc complex.
Fig. 3
Fig. 3
Structure of (Art/Zn) novel complex.
Fig. 4
Fig. 4
IR of (A) Art, (B) Art/Zn complex.
Fig. 5
Fig. 5
XRD of Art/Zn novel complex.
Fig. 6
Fig. 6
SEM of (A) Art, (B) Art/Zn complex.
Fig. 7
Fig. 7
TEM of (A) Art, (B) Art/Zn complex.
Fig. 8
Fig. 8
Cytotoxicity concentration 50 (CC50) and inhibitory concentration 50 (IC50) values for (Art/Zn) metal complex formula revealing its moderate activity against SARS-CoV-2. IC50 was calculated by the best line drawn between log concentration and viral inhibition % (triplicate for each concentration) to evaluate the antiviral activity against SARS-CoV-2 [hCoV-19/Egypt/NRC-03/2020 (Accession Number on GSAID: EPI_ISL_430820)] using Vero E6 cells. *Graph of the cytotoxicity concentration 50 (CC50) of Vero E6 cells. *Graph of the inhibitory concentration 50 (IC50): antiviral activity against SARS-CoV-2.
Fig. 9
Fig. 9
3D pictures of the synthesised compound and scores of the binding interaction, the amino acids, and bonds of the synthesised Art/Zn inside the ACE2 receptor of SARS-CoV-2 (V: View) 4 views (frontal view, side view, dorsal view and ventral view), the positioning and the interactions at the SARS-CoV-2 ACE2 receptor, with the ligand formula (Art/Zn). (A) Co-crystallized formula formed H-bonds with (TYR520, ASN586,Glu 557, MET299, LEU 427 and ILE367). (B) Co-crystallized formula formed H-bonds with (TYR520, SER284, PRO407, ILG-1H6, LIG1.C19,ASP453, LIG1C9 and HSD543). (C) Co-crystallized formula formed H-bonds with (ILE73,Gly404,Lys368, GLN55, ASN277, ARG, LIG1C and LEU401). (D) Co-crystallized formula formed H-bonds with (TRP602, HSD153, PRO407, ILE270, ARG124, CYS152, ASP218).
Fig. 9
Fig. 9
3D pictures of the synthesised compound and scores of the binding interaction, the amino acids, and bonds of the synthesised Art/Zn inside the ACE2 receptor of SARS-CoV-2 (V: View) 4 views (frontal view, side view, dorsal view and ventral view), the positioning and the interactions at the SARS-CoV-2 ACE2 receptor, with the ligand formula (Art/Zn). (A) Co-crystallized formula formed H-bonds with (TYR520, ASN586,Glu 557, MET299, LEU 427 and ILE367). (B) Co-crystallized formula formed H-bonds with (TYR520, SER284, PRO407, ILG-1H6, LIG1.C19,ASP453, LIG1C9 and HSD543). (C) Co-crystallized formula formed H-bonds with (ILE73,Gly404,Lys368, GLN55, ASN277, ARG, LIG1C and LEU401). (D) Co-crystallized formula formed H-bonds with (TRP602, HSD153, PRO407, ILE270, ARG124, CYS152, ASP218).
Fig. 10
Fig. 10
3D picture of the synthesised compound and scores of interaction, amino acids, and bonds of the synthesised Art/Zn inside the Mpro receptor of SARS-CoV-2 (V: View) (frontal view, dorsal view, horizontal view, ventral view and side views), the main protease active site of SARS-CoV-2, the positioning and the interactions and at the SARS-CoV-2Mpro receptor, with the ligand formula (Art/Zn). (A) Co-crystallized formula formed H-bonds with different seven views. (B) Co-crystallized formula formed H-bonds with SER254,ASN51.CA, PHE291,VAL261,Gly146, PHE134,THR98 and PRO132. (C) Co-crystallized formula formed H-bonds with LYS102, MET235, Gly146,Val303, ASP176, LEU177, ALA255 and SER81.
Fig. 10
Fig. 10
3D picture of the synthesised compound and scores of interaction, amino acids, and bonds of the synthesised Art/Zn inside the Mpro receptor of SARS-CoV-2 (V: View) (frontal view, dorsal view, horizontal view, ventral view and side views), the main protease active site of SARS-CoV-2, the positioning and the interactions and at the SARS-CoV-2Mpro receptor, with the ligand formula (Art/Zn). (A) Co-crystallized formula formed H-bonds with different seven views. (B) Co-crystallized formula formed H-bonds with SER254,ASN51.CA, PHE291,VAL261,Gly146, PHE134,THR98 and PRO132. (C) Co-crystallized formula formed H-bonds with LYS102, MET235, Gly146,Val303, ASP176, LEU177, ALA255 and SER81.
Fig. 11
Fig. 11
Histogram for the tested ligand (Art/Zn) interactions with the SARS-CoV-2 receptors during the simulation (100 ns) for (A) ACE2, (B) MPro receptors.
Fig. 12
Fig. 12
Heat map for SARS-CoV-2 receptors and Art/Zn (Simulation 100 ns) for (A) ACE, (B) MPro.
Fig. 13
Fig. 13
Ligand properties during simulation (100 ns) for receptors (A) ACE2, (B) MPro.
Fig. 14
Fig. 14
The RMSD of the Art/Zn complex for the SARS-CoV receptor (A) ACE2 and (B) MPro and of RMSD of Cα atoms of the complexes against simulation (100 ns).
Fig. 15
Fig. 15
Ligand torsion profile with (A) ACE2 and (B) MPro.
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References

    1. Rahman M., Bibi S., Rahaman S., Rahman F., Islam F., Khan M.S., Hasan M.M., Parvez A., Hossain A., Maeesa S.K., Islam R., Najda A., Al-Malky H.S., Mohamed H.R.H., Al-Gwaiz H.I.M., Awaji A.A., Germoush M.O., Kensara O.A., Abdel-Daim M.M., Saeed M., Kamal M.A. Natural therapeutics and nutraceuticals for lung diseases: traditional significance, phytochemistry, and pharmacology. Biomed. Pharmacother. 2022;150 - PubMed
    1. Ito K., Ito M., Elliott W.M., Cosio B., Caramori G., Kon O.M., et al. Decreased histone deacetylase activity in chronic obstructive pulmonary disease. N. Engl. J. Med. 2005;352(19):1967–1976. - PubMed
    1. Prasher P., Sharma M., Mehta M., Paudel K.R., Satija S., Chellappan D.K., et al. Plants derived therapeutic strategies targeting chronic respiratory diseases: chemical and immunological perspective. Chem. Biol. Interact. 2020 - PMC - PubMed
    1. Murphy D.M., O'Byrne P.M. Recent advances in the pathophysiology of asthma. Chest. 2010;137(6):1417–1426. - PubMed
    1. Santana F.P.R., Pinheiro N.M., Mernak M.I.B., Righetti R.F., Martins M.A., Lago J.H., et al. Evidences of herbal medicine-derived natural products effects in inflammatory lung diseases. Mediat. Inflamm. 2016:2016. - PMC - PubMed

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