CORona Drug InTEractions database
A multi-stage virtual screening of FDA-approved drugs reveals potential inhibitors of SARS-CoV-2 main protease
Yasmine M. Mandour, Darius P. Zlotos, M. Alaraby Salem
Abstract
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health emergency. Repurposing of approved pharmaceutical drugs for COVID-19 treatment represents an attractive approach to quickly identify promising drug candidates. SARS-CoV-2 main protease (Mpro) is responsible for the maturation of viral functional proteins making it a key antiviral target. Based on the recently revealed crystal structures of SARS-CoV-2 Mpro, we herein describe a multi-stage virtual screening protocol including pharmacophore screening, molecular docking and protein-ligand interaction fingerprints (PLIF) post-docking filtration for efficient enrichment of potent SARS-CoV-2 Mpro inhibitors. Potential hits, along with a cocrystallized control were further studied via molecular dynamics. A 150-ns production trajectory was followed by RMSD, free energy calculation, and H-bond analysis for each compound. The applied virtual screening protocol led to identification of five FDA-approved drugs with promising binding modes to key subsites of the substrate-binding pocket of SARS-CoV-2 Mpro. The identified compounds belong to different pharmaceutical classes, including several protease inhibitors, antineoplastic agents and a natural flavonoid. The drug candidates discovered in this study present a potential extension of the recently reported SARS-CoV-2 Mpro inhibitors that have been identified using other virtual screening protocols and may be repurposed for COVID-19 treatment.
Source: PubMed
Related molecules
Related interactions
| Target | Drug | Type | Result |
|---|---|---|---|
| 3C-like protease | Boceprevir | ||
| 3C-like protease | Nelfinavir | ||
| 3C-like protease | Rutin | ||
| 3C-like protease | Epirubicin | ||
| 3C-like protease | Thymopentin | ||
| 3C-like protease | Bortezomib |
| Target | Target affiliation | Drug | Type | Result |
|---|---|---|---|---|
| Target | Target affiliation | Drug | Type | Result |
| Name | Synonyms | Genes | Origin |
|---|---|---|---|
| Name | Synonyms | Genes | Origin |
| Name | Synonyms | PubChem | DrugBank | RCSB PDB | ATC |
|---|---|---|---|---|---|
| Name | Synonyms | PubChem | DrugBank | RCSB PDB | ATC |
| Title | Authors | DOI | Source | Article type | Date |
|---|---|---|---|---|---|
| Title | Authors | DOI | Source | Article type | Date |
| Title | Status | Phases | Start Date | Prim. Comp. Date | Comp. Date | First Post. Date |
|---|---|---|---|---|---|---|
| Title | Status | Phases | Start Date | Prim. Comp. Date | Comp. Date | First Post. Date |
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