Abstract
Discovering efficient drugs and identifying target proteins are still an unmet but urgent need for curing coronavirus disease 2019 (COVID-19). Protein structure-based docking is a widely applied approach for discovering active compounds against drug targets and for predicting potential targets of active compounds. However, this approach has its inherent deficiency caused by e.g. various different conformations with largely varied binding pockets adopted by proteins, or the lack of true target proteins in the database. This deficiency may result in false negative results. As a complementary approach to the protein structure-based platform for COVID-19, termed as D3Docking in our previous work, we developed in this study a ligand-based method, named D3Similarity, which is based on the molecular similarity evaluation between the submitted molecule(s) and those in an active compound database. The database is constituted by all the reported bioactive molecules against the coronaviruses, viz., severe acute respiratory syndrome coronavirus (SARS), Middle East respiratory syndrome coronavirus (MERS), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human betacoronavirus 2c EMC/2012 (HCoV-EMC), human CoV 229E (HCoV-229E) and feline infectious peritonitis virus (FIPV), some of which have target or mechanism information but some do not. Based on the two-dimensional (2D) and three-dimensional (3D) similarity evaluation of molecular structures, virtual screening and target prediction could be performed according to similarity ranking results. With two examples, we demonstrated the reliability and efficiency of D3Similarity by using 2D × 3D value as score for drug discovery and target prediction against COVID-19. The database, which will be updated regularly, is available free of charge at https://www.d3pharma.com/D3Targets-2019-nCoV/D3Similarity/index.php.
Keywords: COVID-19; D3Similarity; database; target prediction; virtual screening.
【저자키워드】 COVID-19, Virtual screening, database, D3Similarity, target prediction, 【초록키워드】 coronavirus disease, SARS-CoV-2, Coronavirus disease 2019, Coronaviruses, coronavirus, Drug discovery, reliability, Virtual screening, Proteins, drug, docking, MERS, severe acute respiratory syndrome Coronavirus, virus, Betacoronavirus, Protein, HCoV, Middle East respiratory syndrome Coronavirus, drug target, protein structure, HCoV-229E, target, molecular, information, platform, mechanism, compounds, False negative, structures, similarity, Efficiency, complementary, Middle East, free of charge, Feline infectious peritonitis, deficiency, two-dimensional, acute respiratory syndrome, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, Compound, conformation, binding pocket, target proteins, respiratory syndrome coronavirus, target protein, false negative results, human CoV, charge, HCoV-EMC, approach, human betacoronavirus, human CoV 229E, performed, lack, caused, reported, applied, demonstrated, adopted, submitted, inherent, 【제목키워드】 drug target, approach,