Database Commons

a catalog of worldwide biological databases

Helicases have emerged as promising targets in antiviral drug development but remain largely undrugged. To support the focused development of viral helicase inhibitors we identified, collected, and integrated all chemogenomics data for all helicases annotated in the ChEMBL database. After thoroughly curating and enriching the data with accurate annotations we have created a derivative database of helicase inhibitors which we dubbed Heli-SMACC (Helicase-targeting SMAll Molecule Compound Collection). Heli-SMACC contains 13,597 molecules, 29 proteins, and 20,431 bioactivity entries for viral, human, and bacterial helicases. We selected 30 compounds with promising viral helicase activity and tested them in a SARS-CoV-2 NSP13 ATPase assay. Twelve compounds demonstrated ATPase inhibition and a consistent dose-response curve. While Heli-SMACC provides a rich resource for identifying candidate inhibitors, cross-species compound transferability remains a significant challenge. In particular, inhibitory activity observed against viral helicases often does not translate well to human or bacterial homologs and vice versa due to differences in binding site composition, helicase structure, and cofactor dependencies. Despite these limitations, Heli-SMACC offers a valuable starting point for structure-based optimization and target-specific inhibitor design. The Heli-SMACC database may serve as a reference for virologists and medicinal chemists working on the development of novel helicase inhibitors. Heli-SMACC is publicly available at https://smacc.mml.unc.edu.

The recent severe acute respiratory syndrome coronavirus 2 pandemic has clearly exemplified the need for broad-spectrum antiviral (BSA) medications. However, previous outbreaks show that about one year after an outbreak, interest in antiviral research diminishes and the work toward an effective medication is left unfinished. Martin et al. endeavored to support the early stages of focused BSA development by creating the Small Molecule Antiviral Compound Collection (SMACC), which is publicly available online at https://smacc.mml.unc.edu. SMACC is a highly curated database with over 32,500 entries of chemical compounds tested in both phenotypic and target-based assays across 13 viruses from the NIAID's list of emerging infectious diseases/pathogens. The authors advise judicious use of knowledge collections such as SMACC and recommend users critically evaluate retrieved data and resulting hypotheses prior to experimental testing. When used correctly, SMACC-like databases may serve as a reference for medicinal chemists and virologists working to develop novel BSA medications. To summarize, we emphasize the importance of data curation for both novel outbreak prediction and development of BSAs against these outbreaks.

Diseases caused by new viruses cost thousands if not millions of human lives and trillions of dollars. We have identified, collected, curated, and integrated all chemogenomics data from ChEMBL for 13 emerging viruses that hold the greatest potential threat to global human health. By identifying and solving several challenges related to data annotation accuracy, we developed a highly curated and thoroughly annotated database of compounds tested in both phenotypic and target-based assays for these viruses that we dubbed SMACC (Small Molecule Antiviral Compound Collection). The pilot version of the SMACC database contains over 32,500 entries for 13 viruses. By analyzing data in SMACC, we have identified ∼50 compounds with polyviral inhibition profile, mostly covering flavi- and coronaviruses. The SMACC database may serve as a reference for virologists and medicinal chemists working on the development of novel BSA agents in preparation for future viral outbreaks. SMACC is publicly available at https://smacc.mml.unc.edu.

Diseases caused by new viruses costs thousands if not millions of human lives and trillions of dollars in damage to the global economy. Despite the rapid development of vaccines for SARS-CoV-2, the lack of small molecule antiviral drugs that work against multiple viral families (broad-spectrum antivirals; BSAs) has left the entire world’s human population vulnerable to the infection between the beginning of the outbreak and the widespread availability of vaccines. Developing BSAs is an attractive, yet challenging, approach that could prevent the next, inevitable, viral outbreak from becoming a global catastrophe. To explore whether historical medicinal chemistry efforts suggest the possibility of discovering novel BSAs, we (i) identified, collected, curated, and integrated all chemical bioactivity data available in ChEMBL for molecules tested in respective assays for 13 emerging viruses that, based on published literature, hold the greatest potential threat to global human health; (ii) identified and solved the challenges related to data annotation accuracy including assay description ambiguity, missing cell or target information, and incorrect BioAssay Ontology (BAO) annotations; (iii) developed a highly curated and thoroughly annotated database of compounds tested in both phenotypic (21,392 entries) and target-based (11,123 entries) assays for these viruses; and (iv) identified a subset of compounds showing BSA activity. For the latter task, we eliminated inconclusive and annotated duplicative entries by checking the concordance between multiple assay results and identified eight compounds active against 3-4 viruses from the phenotypic data, 16 compounds active against two viruses from the target-based data, and 35 compounds active in at least one phenotypic and one target-based assay. The pilot version of our SMACC (Small Molecule Antiviral Compound Collection) database contains over 32,500 entries for 13 viruses. Our analysis indicates that previous research yielded very small number of BSA compounds. We posit that focused and coordinated efforts strategically targeting the discovery of such agents must be established and maintained going forward. The SMACC database publicly available at https://smacc.mml.unc.edu may serve as a reference for virologists and medicinal chemists working on the development of novel BSA agents in preparation for future viral outbreaks.