Discovery of Potent Neuraminidase Inhibitors Using a Combination of Pharmacophore-Based Virtual Screening and Molecular Simulation Approach.

Discovery of Potent Neuraminidase Inhibitors Using a Combination of Pharmacophore-Based Virtual Screening and Molecular Simulation Approach.
Appl Biochem Biotechnol. 2017 Oct 23;:
Authors: K R, V S
Abstract
Neuraminidase (NA), a surface protein, facilitates the release of nascent virus and thus spreads infection. It has been renowned as a potential drug target for influenza A virus infection. The drugs such as oseltamivir, zanamivir, peramivir, and laninamivir are approved for the treatment of influenza infection. Additionally, investigational drugs namely MK2206, tamiphosphor, crenatoside, and dehydroepiandrosterone (DHEA) are also available for the treatment. However, recent outbreaks of highly pathogenic and drug-resistant influenza A strains highlighted the need to discover novel NA inhibitor. Keeping this in mind, in the current investigation, an effort was made to ascertain potent inhibitors using pharmacophore-based virtual screening and docking approach. A 3D pharmacophore model was generated based on the chemical features of approved and investigational NA inhibitors using PHASE module of Schrödinger suite. The model consists of two hydrogen bond acceptors (A), one hydrogen bond donor (D), and one positively charged group (P), AADP. Subsequently, molecules with same pharmacophoric features were screened from among the two million compounds available in the ZINC database using the generated pharmacophore hypothesis. Ligand f...

Source: Applied Biochemistry and Biotechnology - October 23, 2017 Category: Biochemistry Authors: K R, V S Tags: Appl Biochem Biotechnol Source Type: research