Tree-Based QSAR Model for Drug Repurposing in the Discovery of New Antibacterial Compounds Against Escherichia coli.

Drug repurposing appears as an increasing popular tool in the search of new treatment options against bacteria. In this paper, a tree-based classification method using Linear Discriminant Analysis (LDA) and discrete indexes was used to create a QSAR (Quantitative Structure-Activity Relationship) model to predict antibacterial activity against Escherichia coli. The model consists on a hierarchical decision tree in which a discrete index is used to divide compounds into groups according to their values for said index in order to construct probability spaces. The second step consists in the calculation of a discriminant function which determines the prediction of the model. The model was used to screen the DrugBank database, identifying 134 drugs as possible antibacterial candidates. Out of these 134 drugs, 8 were antibacterial drugs, 67 were drugs approved for different pathologies and 55 were drugs in experimental stages. This methodology has proven to be a viable alternative to the traditional methods used to obtain prediction models based on LDA and its application provides interesting new drug candidates to be studied as repurposed antibacterial treatments. Furthermore, the topological indexes Nclass and Numhba have proven to have the ability to group active compounds effectively, which suggests a close relationship between them and the antibacterial activity of compounds against E. coli.

Hepatitis E: latest developments in knowledge.

Hepatitis E, caused by Hepatitis E virus (HEV), is a highly prevalent disease in developing countries. In developed nations, autochthonous HEV infections seem to be an emergent disease. Its clinical manifestations and epidemiology are well known for endemic countries. It has been confirmed that hepatitis E is a zoonosis and that parenteral transmission can also occur. The molecular mechanisms of HEV replication are not fully understood, mostly because there are no efficient cell culture systems. HEV can cause chronic hepatitis in organ transplant recipients and immunocompetent patients. Cases with fulminant hepatitis and other extrahepatic manifestations have also been reported. The diagnosis is based on serological studies and detection of HEV RNA in blood and feces. Treatment with ribavirin and/or pegylated-IFN-α have proven to be successful in some cases. The recently approved/marketed vaccine is a good option in order to prevent this infection.