tetano
Editor, Senior Moderator
Mol Divers. 2015 Dec 21. [Epub ahead of print]
[h=1]Discovery of Influenza A virus neuraminidase inhibitors using support vector machine and Na?ve Bayesian models.[/h] Lian W[SUP]1[/SUP], Fang J[SUP]1[/SUP], Li C[SUP]1[/SUP], Pang X[SUP]1[/SUP], Liu AL[SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Du GH[SUP]5,[/SUP][SUP]6,[/SUP][SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Neuraminidase (NA) is a critical enzyme in the life cycle of influenza virus, which is known as a successful paradigm in the design of anti-influenza agents. However, to date there are no classification models for the virtual screening of NA inhibitors. In this work, we built support vector machine and Na?ve Bayesian models of NA inhibitors and non-inhibitors, with different ratios of active-to-inactive compounds in the training set and different molecular descriptors. Four models with sensitivity or Matthews correlation coefficients greater than 0.9 were chosen to predict the NA inhibitory activities of 15,600 compounds in our in-house database. We combined the results of four optimal models and selected 60 representative compounds to assess their NA inhibitory profiles in vitro. Nine NA inhibitors were identified, five of which were oseltamivir derivatives with large C-5 substituents exhibiting potent inhibition against H1N1 NA with [Formula: see text] values in the range of 12.9-185.0 nM, and against H3N2 NA with [Formula: see text] values between 18.9 and 366.1 nM. The other four active compounds belonged to novel scaffolds, with [Formula: see text] values ranging 39.5-63.8 [Formula: see text]M against H1N1 NA and 44.5-114.1 [Formula: see text]M against H3N2 NA. This is the first time that classification models of NA inhibitors and non-inhibitors are built and their prediction results validated experimentally using in vitro assays.
[h=4]KEYWORDS:[/h] H1N1; H3N2; Influenza virus; Na?ve Bayesian; Neuraminidase inhibitor; SVM; Support vector machine; Virtual screening
PMID: 26689205 [PubMed - as supplied by publisher]
[h=1]Discovery of Influenza A virus neuraminidase inhibitors using support vector machine and Na?ve Bayesian models.[/h] Lian W[SUP]1[/SUP], Fang J[SUP]1[/SUP], Li C[SUP]1[/SUP], Pang X[SUP]1[/SUP], Liu AL[SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Du GH[SUP]5,[/SUP][SUP]6,[/SUP][SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Neuraminidase (NA) is a critical enzyme in the life cycle of influenza virus, which is known as a successful paradigm in the design of anti-influenza agents. However, to date there are no classification models for the virtual screening of NA inhibitors. In this work, we built support vector machine and Na?ve Bayesian models of NA inhibitors and non-inhibitors, with different ratios of active-to-inactive compounds in the training set and different molecular descriptors. Four models with sensitivity or Matthews correlation coefficients greater than 0.9 were chosen to predict the NA inhibitory activities of 15,600 compounds in our in-house database. We combined the results of four optimal models and selected 60 representative compounds to assess their NA inhibitory profiles in vitro. Nine NA inhibitors were identified, five of which were oseltamivir derivatives with large C-5 substituents exhibiting potent inhibition against H1N1 NA with [Formula: see text] values in the range of 12.9-185.0 nM, and against H3N2 NA with [Formula: see text] values between 18.9 and 366.1 nM. The other four active compounds belonged to novel scaffolds, with [Formula: see text] values ranging 39.5-63.8 [Formula: see text]M against H1N1 NA and 44.5-114.1 [Formula: see text]M against H3N2 NA. This is the first time that classification models of NA inhibitors and non-inhibitors are built and their prediction results validated experimentally using in vitro assays.
[h=4]KEYWORDS:[/h] H1N1; H3N2; Influenza virus; Na?ve Bayesian; Neuraminidase inhibitor; SVM; Support vector machine; Virtual screening
PMID: 26689205 [PubMed - as supplied by publisher]