Hybrid Machine Learning and Experimental Studies of Antiviral Potential of Ionic Liquids against P100, MS2, and Phi6.

Viruses are a group of widespread organisms that are often responsible for very dangerous diseases, as most of them follow a mechanism to multiply and infect their hosts as quickly as possible. Pathogen viruses also mutate regularly, with the result that measures to prevent virus transmission and recover from the disease caused are often limited. The development of new substances is very time-consuming and highly budgeted and requires the sacrifice of many living organisms. Computational chemistry methods allow faster analysis at a much lower cost and, most importantly, reduce the number of living organisms sacrificed experimentally to a minimum. Ionic liquids (ILs) are a group of chemical compounds that could potentially find a wide range of applications due to their potential virucidal activity. In our study, we conducted a complex computational analysis to predict the antiviral activity of ionic liquids against three surrogate viruses: two nonenveloped viruses, Listeria monocytogenes phage P100 and Escherichia coli phage MS2, and one enveloped virus, Pseudomonas syringae phage Phi6. Based on experimental data of toxic activity (logEC90), we assigned activity classes to 154 ILs. Prediction models were created and validated according to the Organization for Economic Co-operation and Development (OECD) recommendations using the Classification Tree method. Further, we performed an external validation of our models through virtual screening on a set of 1277 theoretically generated ionic liquids and then selected 10 active ionic liquids, which were synthesized to verify their activity against the analyzed viruses. Our study proved the effectiveness and efficiency of computational methods to predict the antiviral activity of ionic liquids. Thus, computational models are a cost-effective alternative approach compared with time-consuming experimental studies where live animals are involved.

How the Structure of Per- and Polyfluoroalkyl Substances (PFAS) Influences Their Binding Potency to the Peroxisome Proliferator-Activated and Thyroid Hormone Receptors-An In Silico Screening Study.

In this study, we investigated PFAS (per- and polyfluoroalkyl substances) binding potencies to nuclear hormone receptors (NHRs): peroxisome proliferator-activated receptors (PPARs) α, ß, and γ and thyroid hormone receptors (TRs) α and ß. We have simulated the docking scores of 43 perfluoroalkyl compounds and based on these data developed QSAR (Quantitative Structure-Activity Relationship) models for predicting the binding probability to five receptors. In the next step, we implemented the developed QSAR models for the screening approach of a large group of compounds (4464) from the NORMAN Database. The in silico analyses indicated that the probability of PFAS binding to the receptors depends on the chain length, the number of fluorine atoms, and the number of branches in the molecule. According to the findings, the considered PFAS group bind to the PPARα, ß, and γ only with low or moderate probability, while in the case of TR α and ß it is similar except that those chemicals with longer chains show a moderately high probability of binding.