Computer-Aided Drug Design of Neuraminidase Inhibitors and MCL-1 Specific Drugs

Abstract

Computational methods have been applied to many drug discovery projects. In this study computational methods were applied to: 1) develop pan neuraminidase inhibitors 2) analyze the role of rhodanine scaffold in selective inhibition of MCL-1.

Influenza is a contagious viral disease of respiratory tract with oseltamivir and zanamivir as only two FDA approved drugs. However, mutations like H274Y, N294S and R292K have resulted in resistance. In first phase of the study, QSAR model was developed to screen potential neuraminidase inhibitors (PNI). The PNI were later docked against group I/II, wild and mutant neuraminidase strains.

Apoptosis is mainly regulated by BCL2 protein family. BCL2 family can be divided into apoptotic or anti-apoptotic proteins. Anti-apoptotic protein like BCL-XL has been a target of number of anti-cancer drugs. However, MCL-1 overexpression has led to the resistance. Docking and molecular dynamics was performed to analyze the interactions of MCL-1 with compounds of different scaffolds.