SWEETLEAD: an In Silico Database of Approved Drugs, Regulated Chemicals, and Herbal Isolates for Computer-Aided Drug Discovery

Abstract

In the face of drastically rising drug discovery costs, strategies promising to reduce development timelines and expenditures are being pursued. Computer-aided virtual screening and repurposing approved drugs are two such strategies that have shown recent success. Herein, we report the creation of a highly-curated in silico database of chemical structures representing approved drugs, chemical isolates from traditional medicinal herbs, and regulated chemicals, termed the SWEETLEAD database. The motivation for SWEETLEAD stems from the observance of conflicting information in publicly available chemical databases and the lack of a highly curated database of chemical structures for the globally approved drugs. A consensus building scheme surveying information from several publicly accessible databases was employed to identify the correct structure for each chemical. Resulting structures are filtered for the active pharmaceutical ingredient, standardized, and differing formulations of the same drug were combined in the final database. The publically available release of SWEETLEAD (https://simtk.org/home/sweetlead) provides an important tool to enable the successful completion of computer-aided repurposing and drug discovery campaigns.

Crystal violet structural analogues identified by in silico drug repositioning present anti-Trypanosoma cruzi activity through inhibition of proline transporter TcAAAP069

“…Similarity screening search was performed using the CV structure as reference (query) compound (ZINC ID: 13763987). Structures (≈ 10,000) were obtained from the highly curated “Sweetlead” database of world’s approved medicines, illegal drugs, and isolates from traditional medicinal herbs (34). The screening was performed using the softwares LiSiCA v1.0 (35) (Ligand Similarity using Clique Algorithm), KCOMBU (36) (K(ch)emical structure COMparison using the BUild-up algorithm), ShaEP (37) (Molecular Overlay Based on Shape and Electrostatic Potential) v 1.1.2, and Shape-it v 1.0.1 (38) (Gaussian volumes as descriptor for molecular shape).…”

Crystal violet structural analogues identified by in silico drug repositioning present anti-Trypanosoma cruzi activity through inhibition of proline transporter TcAAAP069

“…Similarity screening search was performed using the CV structure as reference (query) compound (ZINC ID: 13763987). Structures (� 10,000) were obtained from the highly curated "Sweetlead" database of world's approved medicines, illegal drugs, and isolates from traditional medicinal herbs [39]. The screening was performed using the softwares LiSiCA v1.0 [40] (Ligand Similarity using Clique Algorithm), KCOMBU [41] (K(ch)emical structure COMparison using the BUild-up algorithm), ShaEP [42] (Molecular Overlay Based on Shape and Electrostatic Potential) v 1.1.2, and Shape-it v 1.0.1 [43] (Gaussian volumes as descriptor for molecular shape).…”

Targeting furin activity through in silico and in vitro drug repurposing strategy for SARS-CoV-2 spike glycoprotein cleavage repression

“…We rst generated a hand-curated database of approved and investigational drugs (small molecules). Over 20,000 non-unique approved and investigational compounds (experimental molecules were not included initially as we were interested in molecules that are approved or have entered clinical trials) were rst downloaded from the last released of DrugBank 25 , DrugCentral 26 , and SWEETLEAD 27 . 17449 additional molecules were extracted from Wikipedia Chemical Structures using utilities implemented in the DataWarrior package 28 .…”