The novel coronavirus pneumonia COVID-19 infected by SARS-CoV-2 has attracted worldwide attention. It is urgent to find effective therapeutic strategies for stopping COVID-19. In this study, a Bounded Nuclear Norm Regularization (BNNR) method is developed to predict anti-SARS-CoV-2 drug candidates. First, three virus-drug association datasets are compiled. Second, a heterogeneous virus-drug network is constructed. Third, complete genomic sequences and Gaussian association profiles are integrated to compute virus similarities; chemical structures and Gaussian association profiles are integrated to calculate drug similarities. Fourth, a BNNR model based on kernel similarity (VDA-GBNNR) is proposed to predict possible anti-SARS-CoV-2 drugs. VDA-GBNNR is compared with four existing advanced methods under fivefold cross-validation. The results show that VDA-GBNNR computes better AUCs of 0.8965, 0.8562, and 0.8803 on the three datasets, respectively. There are 6 anti-SARS-CoV-2 drugs overlapping in any two datasets, that is, remdesivir, favipiravir, ribavirin, mycophenolic acid, niclosamide, and mizoribine. Molecular dockings are conducted for the 6 small molecules and the junction of SARS-CoV-2 spike protein and human angiotensin-converting enzyme 2. In particular, niclosamide and mizoribine show higher binding energy of −8.06 and −7.06 kcal/mol with the junction, respectively. G496 and K353 may be potential key residues between anti-SARS-CoV-2 drugs and the interface junction. We hope that the predicted results can contribute to the treatment of COVID-19.
【저자키워드】 SARS-CoV-2, virus-drug association, molecular docking, FDA-approved drugs, bounded nuclear norm regularization, 【초록키워드】 COVID-19, Treatment, Structure, Pneumonia, drugs, Remdesivir, Favipiravir, drug, docking, virus, anti-SARS-CoV-2, ribavirin, binding energy, Novel coronavirus, SARS-CoV-2 spike protein, dataset, small molecule, predict, therapeutic strategy, association, similarity, AUC, overlapping, profile, drug candidates, residue, human Angiotensin-converting enzyme, similarities, heterogeneous, datasets, norm, second, G496, genomic sequence, Complete, effective, K353, predicted, conducted, contribute, calculate, mizoribine, 【제목키워드】 COVID-19, drug, Screening, norm, Potential, Bound,