Exploring the antiviral activity of α-ketoamides compounds through electronic structure calculations: a structure-activity relationship study.

In recent years, the scientific community has worked intensively in the search and development of new drugs to suppress viral infections, such as COVID-19. In fact, a number of active compounds have been tested; however, the absence of significant structure-activity relationships hinders the production of optimized drugs. In this study, molecular modeling techniques were employed to investigate the electronic, structural and chemical reactivity properties of a set α-ketoamides whose antiviral activities have been reported in the literature, aiming to propose new promising derivatives. The local reactivity of the compounds was evaluated via condensed-to-atoms Fukui indexes and molecular electrostatic potential. Multivariate data analysis and random forests machine learning techniques were employed to correlate the antiviral properties and electronic and structural descriptors and identify relevant variables. A series of new derivatives were then proposed and evaluated via density functional theory-based calculations, and docking/molecular dynamics with the target protein of the virus. The results suggest that active derivatives present reduced reactivity towards electrophilic agents on the central core of the molecules and high reactivity on R1 ligands. Derivatives with higher predicted antiviral activities were proposed based on simple electronic descriptors, and their efficacies are reinforced by docking and molecular dynamics simulations.Communicated by Ramaswamy H. Sarma.

Objective evaluation of immediate reading skin prick test applying image planimetric and reaction thermometry analyses.

The skin prick test is used to diagnose patients' sensitization to antigens through a mediated IgE response. It is a practical and quick exam, but its diagnosis depends on instruments for measuring the allergic response and observer's interpretation. The conventional method for inferring about the allergic reaction is performed from the dimensions of the wheals, which are measured using a ruler or a caliper. To make this diagnosis less dependent on human interpretation, the present study proposes two alternative methods to infer about the allergic reaction: computational determination of the wheal area and a study of the temperature variation of the patient's skin in the puncture region. For this purpose, prick test using histamine was performed on 20 patients randomly selected. The areas were determined by the conventional method using the dimensions of the wheals measured with a digital caliper 30 min after the puncture. The wheal areas were also determined by a Python algorithm using photographs of the puncture region obtained with a smartphone. A variable named circularity deviation was also determined for each analyzed wheal. The temperature variation was monitored using an infrared temperature sensor, which collected temperature data for 30 min. All results were statistically compared or correlated. The results showed that the computational method to infer the wheal areas did not differ significantly from the areas determined by the conventional method (p-value = 0.07585). Temperature monitoring revealed that there was a consistent temperature increase in the first minutes after the puncture, followed by stabilization, so that the data could be adjusted by a logistic equation (R2 = 0.96). This adjustment showed that the optimal time to measure the temperature is 800 s after the puncture, when the temperature stabilization occurs. The results have also shown that this temperature stabilization has a significant positive correlation with wheal area (p-value = 0.0015). Thus, we concluded that the proposed computational method is more accurate to infer the wheal area when compared to the traditional method, and that the temperature may be used as an alternative parameter to infer about the allergic reaction.