CORona Drug InTEractions database
Metal-Bound Methisazone; Novel Drugs Targeting Prophylaxis and Treatment of SARS-CoV-2, a Molecular Docking Study
Ahmed Abdelaal Ahmed Mahmoud M. Alkhatip, Michail Georgakis, Lucio R. Montero Valenzuela, Mohamed Hamza, Ehab Farag, Jaqui Hodgkinson, Hisham Hosny, Ahmed M. Kamal, Mohamed Wagih, Amr Naguib, Hany Yassin, Haytham Algameel, Mohamed Elayashy, Mohamed Abdelhaq, Mohamed I. Younis, Hassan Mohamed, Mohammed Abdulshafi, Mohamed A. Elramely
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.
Source: PMC
Related molecules
Related interactions
Target | Drug | Type | Result |
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Spike glycoprotein | Methisazone | ||
Papain-like proteinases 1/2 | Methisazone |
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CORDITE (CORona Drug InTEractions database) collects and aggregates data from PubMed, MedRxiv, BioRxiv, ChemRxiv and PMC for SARS-CoV-2. Its main focus is set on drug interactions either addressing viral proteins or human proteins that could be used to treat COVID. It collects and provides up-to-date information on computational predictions, in vitro, as well as in vivo study data.
The information provided is for research only and we cannot guarantee the correctness of the data.
Please contact dominik.heider@uni-muenster.de for further information.
Programmable access
There is an open API for access programmatically to the database. The API will print a JSON output:
- Interactions
https://cordite-api.uni-muenster.de/api.php?action=list&table=interaction
- Targets
https://cordite-api.uni-muenster.de/api.php?action=list&table=target
- Drugs
https://cordite-api.uni-muenster.de/api.php?action=list&table=drug
- Publications
https://cordite-api.uni-muenster.de/api.php?action=list&table=publication
- Clinical trials
https://cordite-api.uni-muenster.de/api.php?action=list&table=clinical_trial