Evaluation of drug-resistant mutations using the Boltzmann distribution and docking simulation

Abstract

Emergence of drug resistant viruses caused by treatments of viral infections is inevitable and the rapid evaluation of drug resistance is a significant subject as a countermeasure. Previously, we developed a novel method for evaluating drug resistance abilities of pathogenic viruses by a docking study, using known crystal structures and the mutation information. In this study, we applied this method to evaluate the abilities of atazanavir as well as oseltamivir in order to extend the scope of this method. First, we tried to evaluate the resistance abilities of atazanavir against 30 kinds of HIV-1 proteases, including a wild type and 29 variants. As a result, it was shown that our method was able to correctly evaluate the highly resistant protease. Secondly, we also applied this method to subtypes H1N1, H3N2, and H5N1 as well as type B neuraminidase, which include the wild type, low-level and high-level resistant variants. Then it was shown that our method was also able to correctly evaluate the highly resistant variants of subtype H1N1 and type B neuraminidase.