Identifying potential entry inhibitors for emerging Nipah virus by molecular docking and chemical-protein interaction network

Abstract

Nipah Virus (NiV) is a newly emergent paramyxovirus that has caused various outbreaks in Asian countries. Despite its acute pathogenicity and lack of approved therapeutics for human use, there is an urgent need to determine inhibitors against NiV. Hence, this work includes prospection of potential entry inhibitors by implementing an integrative structure-and network-based drug discovery approach. FDA-approved drugs were screened against attachment glycoprotein (NiV-G, PDB: 2VSM), one of the prime targets to inhibit viral entry, using a molecular docking approach that was benchmarked both on CCDC/ASTEX and known NIV-G inhibitor set. The predicted small molecules were prioritized on the basis of topological analysis of the chemical-protein interaction network, which was inferred by integrating the drug-target network, NiV-human interaction network, and human proteinprotein interaction network. A total of 17 drugs were predicted to be NiV-G inhibitors using molecular docking studies that were further prioritized to 3 novel leads À Nilotinib, Deslanoside and Acetyldigitoxin À on the basis of topological analysis of inferred chemical-protein interaction network. While Deslanoside and Acetyldigitoxin belong to an already known class of anti-NiV inhibitors, Nilotinib belongs to Benzenoids chemical class that has not been reported hitherto for developing anti-NiV inhibitors. These identified drugs are expected to be successful in further experimental evaluation and therefore could be used for anti-Nipah drug discovery. Apart, we also obtained various insights into the underlying chemical-protein interaction network, based on which several important network nodes were predicted. The applicability of our proposed approach was also demonstrated by prospecting for anti-NiV phytochemicals on an independent dataset.

Identification of CHRNB4 as a Diagnostic/Prognostic Indicator and Therapeutic Target in Human Esophageal Squamous Cell Carcinoma

“…Structure-based molecular docking is conceivably the most reliable and widely implemented approach in the early phase of drug discovery ( 46 ). In our docking results, the top 5 ranked small molecules including Nisin, Enalapril maleate (Vasotec), Mangafodipir Trisodium, Raltitrexed (Tomudex), and Iron sucrose had high docking score with CHRNB4 protein.…”

Computational Identification of Potential Multitarget Inhibitors of Nipah Virus by Molecular Docking and Molecular Dynamics

“…(3) molecular docking-all ligands were docked into the respective ligand-binding sites using the QuickVina v 2.0 [50] software, a docking tool that accelerates AutoDock Vina software [51] by implementing an already benchmarked (on CCDC/ASTEX dataset) molecular docking approach [37]. The small molecules that bind to all the three viral proteins (NiV-G ∩ NiV-F ∩ NiV-N) were considered multitarget inhibitors.…”

“…Our group has developed a resource of multitargeted putative therapeutics and epitopes for NiV drug discovery as well [35]. Additionally, several small-molecule inhibitors were identified by our group using QSAR [36] and molecular docking-based studies [37]. In our previous study [37], we have identified small-molecule FDA-approved drugs as potential inhibitors of NiV-G using an ensemble of molecular docking and analysis of the chemical-protein interaction network.…”

“…Additionally, several small-molecule inhibitors were identified by our group using QSAR [36] and molecular docking-based studies [37]. In our previous study [37], we have identified small-molecule FDA-approved drugs as potential inhibitors of NiV-G using an ensemble of molecular docking and analysis of the chemical-protein interaction network. Computational screening of small-molecule inhibitors/drugs is a useful approach for rapid screening of therapeutic molecules from a large chemical space; this motivated us to shortlist potential leads to meet the urgent demand for repurposing drugs for the treatment of NiV.…”

Targeting Envelope Proteins of Poxviruses to Repurpose Phytochemicals against Monkeypox: An In Silico Investigation

“…Due to their natural existence, easy availability, extensive antimicrobial, antiviral, antivirulence, and pharmacological properties, the application of plant-derived products and bioactive phytochemicals in modern medicine has gained momentum among researchers (Chadha et al, 2021;Chadha et al, 2022a). Numerous in silico and pharmacoinformatics-based reports have predicted the effectiveness of phytochemicals and other drugs against SARS-CoV-2, Ebola, and Nipah virus (Kwofie et al, 2019;Pathania et al, 2019;Choudhury et al, 2021;Kumar et al, 2021a). On similar lines, we employed a comprehensive in silico approach to identify phytochemicals that could potentially act as inhibitors against poxviruses for repurposing them against the MPXV.…”