Targeting the Human Influenza a Virus: The Methods, Limitations, and Pitfalls of Virtual Screening for Drug-like Candidates Including Scaffold Hopping and Compound Profiling.

ABSTRACT: In this study, we describe the input data and processing steps to find antiviral lead compounds by a virtual screen. Two-dimensional and three-dimensional filters were designed based on the X-ray crystallographic structures of viral neuraminidase co-crystallized with substrate sialic acid, substrate-like DANA, and four inhibitors (oseltamivir, zanamivir, laninamivir, and peramivir). As a result, ligand-receptor interactions were modeled, and those necessary for binding were utilized as screen filters. Prospective virtual screening (VS) was carried out in a virtual chemical library of over half a million small organic substances. Orderly filtered moieties were investigated based on 2D- and 3D-predicted binding fingerprints disregarding the "rule-of-five" for drug likeness, and followed by d

SUBMITTER: Scior T 

PROVIDER: S-EPMC10221779 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature