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Article

Metal-Bound Methisazone; Novel Drugs Targeting Prophylaxis and Treatment of SARS-CoV-2, a Molecular Docking Study

by
Ahmed Abdelaal Ahmed Mahmoud M. Alkhatip
1,2,*,
Michail Georgakis
3,
Lucio R. Montero Valenzuela
4,
Mohamed Hamza
5,
Ehab Farag
1,
Jaqui Hodgkinson
6,
Hisham Hosny
5,7,
Ahmed M. Kamal
5,
Mohamed Wagih
5,
Amr Naguib
5,
Hany Yassin
8,
Haytham Algameel
9,
Mohamed Elayashy
5,
Mohamed Abdelhaq
5,
Mohamed I. Younis
10,
Hassan Mohamed
5,11,
Mohammed Abdulshafi
12 and
Mohamed A. Elramely
13
1
Faculty of Medicine, Beni-Suef University, Beni Suef 62511, Egypt
2
Birmingham Children’s Hospital, Birmingham B4 6NH, UK
3
Sinodos Chemistry Company (SinodosChemistry.com), Tenedou 16 str, 54453 Thessaloniki, Greece
4
Instituto de Biotecnología, UNAM (ibt.unam.mx), 62210 Cuernavaca, Mexico
5
Faculty of Medicine, Cairo University, Giza 11562, Egypt
6
Jaqui Hodgkinson Communications, 3722JK Bilthoven, The Netherlands
7
Essex Cardiothoracic Centre, MSE Foundation Trust, Basildon SS16 5NL, UK
8
Faculty of Medicine, Fayoum University, Faiyum 63514, Egypt
9
Aberdeen Royal Infirmary Hospital, Aberdeen AB25 2ZN, UK
10
Cambridge University Hospital, Cambridge CB2 0QQ, UK
11
Leeds General Infirmary Hospital, Leeds LS1 3EX, UK
12
Imam Abdulrahman Bin Faisal University Hospital, University of Dammam, Dammam 34221, Saudi Arabia
13
National Cancer Institute, Cairo University, Giza 11796, Egypt
 
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*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(6), 2977; https://doi.org/10.3390/ijms22062977
Submission received: 18 February 2021 / Revised: 6 March 2021 / Accepted: 11 March 2021 / Published: 15 March 2021
(This article belongs to the Section Biochemistry)
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Abstract

SARS-CoV-2 currently lacks effective first-line drug treatment. We present promising data from in silico docking studies of new Methisazone compounds (modified with calcium, Ca; iron, Fe; magnesium, Mg; manganese, Mn; or zinc, Zn) designed to bind more strongly to key proteins involved in replication of SARS-CoV-2. In this in silico molecular docking study, we investigated the inhibiting role of Methisazone and the modified drugs against SARS-CoV-2 proteins: ribonucleic acid (RNA)-dependent RNA polymerase (RdRp), spike protein, papain-like protease (PlPr), and main protease (MPro). We found that the highest binding interactions were found with the spike protein (6VYB), with the highest overall binding being observed with Mn-bound Methisazone at −8.3 kcal/mol, followed by Zn and Ca at −8.0 kcal/mol, and Fe and Mg at −7.9 kcal/mol. We also found that the metal-modified Methisazone had higher affinity for PlPr and MPro. In addition, we identified multiple binding pockets that could be singly or multiply occupied on all proteins tested. The best binding energy was with Mn–Methisazone versus spike protein, and the largest cumulative increases in binding energies were found with PlPr. We suggest that further studies are warranted to identify whether these compounds may be effective for treatment and/or prophylaxis.
Keywords: COVID-19; SARS-CoV-2; molecular docking; treatment; prophylaxis COVID-19; SARS-CoV-2; molecular docking; treatment; prophylaxis

Share and Cite

MDPI and ACS Style

Abdelaal Ahmed Mahmoud M. Alkhatip, A.; Georgakis, M.; Montero Valenzuela, L.R.; Hamza, M.; Farag, E.; Hodgkinson, J.; Hosny, H.; Kamal, A.M.; Wagih, M.; Naguib, A.; et al. Metal-Bound Methisazone; Novel Drugs Targeting Prophylaxis and Treatment of SARS-CoV-2, a Molecular Docking Study. Int. J. Mol. Sci. 2021, 22, 2977. https://doi.org/10.3390/ijms22062977

AMA Style

Abdelaal Ahmed Mahmoud M. Alkhatip A, Georgakis M, Montero Valenzuela LR, Hamza M, Farag E, Hodgkinson J, Hosny H, Kamal AM, Wagih M, Naguib A, et al. Metal-Bound Methisazone; Novel Drugs Targeting Prophylaxis and Treatment of SARS-CoV-2, a Molecular Docking Study. International Journal of Molecular Sciences. 2021; 22(6):2977. https://doi.org/10.3390/ijms22062977

Chicago/Turabian Style

Abdelaal Ahmed Mahmoud M. Alkhatip, Ahmed, Michail Georgakis, Lucio R. Montero Valenzuela, Mohamed Hamza, Ehab Farag, Jaqui Hodgkinson, Hisham Hosny, Ahmed M. Kamal, Mohamed Wagih, Amr Naguib, and et al. 2021. "Metal-Bound Methisazone; Novel Drugs Targeting Prophylaxis and Treatment of SARS-CoV-2, a Molecular Docking Study" International Journal of Molecular Sciences 22, no. 6: 2977. https://doi.org/10.3390/ijms22062977

APA Style

Abdelaal Ahmed Mahmoud M. Alkhatip, A., Georgakis, M., Montero Valenzuela, L. R., Hamza, M., Farag, E., Hodgkinson, J., Hosny, H., Kamal, A. M., Wagih, M., Naguib, A., Yassin, H., Algameel, H., Elayashy, M., Abdelhaq, M., Younis, M. I., Mohamed, H., Abdulshafi, M., & Elramely, M. A. (2021). Metal-Bound Methisazone; Novel Drugs Targeting Prophylaxis and Treatment of SARS-CoV-2, a Molecular Docking Study. International Journal of Molecular Sciences, 22(6), 2977. https://doi.org/10.3390/ijms22062977

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