1. Introduction of MecDDI

In this study, a database entitled ‘MecDDI’ was introduced to systematically clarify the mechanisms underlying the existing DDIs. This database was unique in (a) clarifying, for the first time, the mechanism underlying over 110,000 DDIs by explicit description and graphic illustration, and (b) providing a systematic classification for all the collected DDIs based on the clarified mechanisms. Due to the long-lasting threats of DDI to public health, MecDDI could offer the medical scientists clear clarification of DDI mechanisms, prepare data for the algorithm scientists to predict new DDI, and support healthcare professionals to identify alternative therapeutics.

2. Search for Particular Drug

2.1 Search by Drug Name

For example, if users want to know detailed information on the particular drug, users can search by entering a drug name in “Search for Drug Interactions” box or by selecting a drug name in the “Search for Drug Entries” box.

2.2 Search by Disease Class

If users want to know detailed information on the particular drug for a disease, the user can search by selecting a disease and selecting a drug of this disease by “Search for Drug Entries by Disease Class”.

2.3 Search by Mechanism Class

If users want to know detailed information on a particular drug for a mechanism class, the user can search by selecting a mechanism and selecting a drug involved in this mechanism by using the " Search for Drug Entries by Mechanism Class".

2.4 Resulting webpage of Particular Drug

The resulting webpage displays a summary of general information about the drug matching the term "Apremilast". By clicking on the hyperlink "Drug Info" button, detailed information on Apremilast together with the list of DDIs for this drug can be recursively searched.

3. Detailed information on Drug page

The Drug page contains mainly “Drug General Information”, “Full list of drugs interacting with this drug” and “Drug-Drug Interaction Network” information. In the "Drug General Information" section, the general data of this drug was provided, including drug name, drug type, synonym, disease indications, therapeutic class, 3D and 2D molecular structures, formula, InChI, InChIKey, SMILES, as well as the external link to the existing databases: PubChem, CAS, ChEBI, TTD, VARIDT & INTEDE. In the "Full list of drugs interacting with this drug" section, the molecular information on these drugs (such as formula and compound ID) and the severity level of the DDI were also provided. Users can click on the ‘Inter Info' button to jump to a new page explicitly describing a particular DDI. In the "Drug-Drug Interaction Network" section, two interactive graphs based on classification were constructed to intuitively describe the distribution of mechanism and the correlation of all DDIs for a studied drug

4. Search for for DDIs

4.1 Search by drug name

All drugs that interact with a particular drug can be searched by entering a drug name in "Search for Drug-Drug Interaction" on the search page. The results page shows a list of DDIs matching "Amprenavir". By clicking on the hyperlinked "Interaction Info" button, corresponding DDI pages can be searched recursively.

4.2 Search by another drug

In “Search for Drug-Drug Interaction by another Drug”, select the name of a drug, and then select the name of another drug interacting with this drug. The results page shows the DDI for "Amprenavir" and "Citalopram". By clicking on the hyperlinked "Interaction Info" button, this DDI page can be searched recursively.

4.3 Search by Mechanism of DDI

In “Search for Drug-Drug Interaction by Mechanism”, select a mechanism of DDI, and then select a related drug pair. The results page shows the DDI for "Amprenavir" and "Citalopram". By clicking on the hyperlinked "Interaction Info" button, this DDI page can be searched recursively.

5. Detailed information on the Interaction page

By clicking the “Interaction info” button, the detailed information page of this DDI will be displayed. Taking the interaction between entacapone and solriamfetol as an example, the corresponding mechanism of this DDI was first described, and the different roles played by two drugs in this DDI were specified based on a comprehensive literature review. Then, the biological functions of any molecules playing essential roles in the mechanisms of this DDI, were explicitly described in the online DDI page, which included protein name, gene name, UniProt ID, KEGG ID, protein family, protein function, etc. In the meantime, both structures and sequences of these essential molecules were collected and provided via clicking ‘Structure’ and ‘Sequence’ buttons in blue dark background. Finally, the summary of the mechanism underlying each DDI was explicitly provided. Moreover, the graphic illustration of the identified mechanism was depicted for each DDI. In addition, the 'Recommended Action' section showed the guidance on the DDI management for the purpose of mitigating potential risks.

6. Browse page

The browse page displays a list of all drugs and a list of DDIs in the database. Click on “Drug info” or “Interaction info” to see more detailed information about a particular drug or DDI.

7. Download page

The Download page allows users to download all Full data from the database.