期刊名称：Computational and Structural Biotechnology Journal
印刷版ISSN：2001-0370
出版年度：2021
卷号：19
页码：3133-3148
DOI：10.1016/j.csbj.2021.05.037
出版社：Computational and Structural Biotechnology Journal
摘要：The world is facing the COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Likewise, other viruses of the Coronaviridae family were responsible for causing epidemics earlier. To tackle these viruses, there is a lack of approved antiviral drugs. Therefore, we have developed robust computational methods to predict the repurposed drugs using machine learning techniques namely Support Vector Machine, Random Forest, k -Nearest Neighbour, Artificial Neural Network, and Deep Learning. We used the experimentally validated drugs/chemicals with anticorona activity (IC 50 /EC 50 ) from ‘DrugRepV’ repository. The unique entries of SARS-CoV-2 (142), SARS (221), MERS (123), and overall Coronaviruses (414) were subdivided into the training/testing and independent validation datasets, followed by the extraction of chemical/structural descriptors and fingerprints (17968). The highly relevant features were filtered using the recursive feature selection algorithm. The selected chemical descriptors were used to develop prediction models with Pearson’s correlation coefficients ranging from 0.60 to 0.90 on training/testing. The robustness of the predictive models was further ensured using external independent validation datasets, decoy datasets, applicability domain, and chemical analyses. The developed models were used to predict promising repurposed drug candidates against coronaviruses after scanning the DrugBank. Top predicted molecules for SARS-CoV-2 were further validated by molecular docking against the spike protein complex with ACE receptor. We found potential repurposed drugs namely Verteporfin, Alatrofloxacin, Metergoline, Rescinnamine, Leuprolide, and Telotristat ethyl with high binding affinity. These ‘anticorona' computational models would assist in antiviral drug discovery against SARS-CoV-2 and other Coronaviruses.
关键词：Coronaviruses ; COVID-19 ; SARS-CoV-2 ; Drug repurposing ; Machine learning ; AI ; Chemical descriptors
