Design and Identification of Lead Compounds Targeting Nipah G Attachment Glycoprotein by In Silico Approaches

Abstract

Nipah virus (NiV) caused several outbreaks in Asian countries, including the latest one from the Kerala state of India. There is no drug available against NiV till now, despite its urgent requirement. There are reports about the anti-influenza viral drug Favipiravir, which has positively affected the Nipah virus in vitro models. In the current work, we have provided a computational screening for NiV inhibitors. Twenty-two designed compounds from favipiravir and Nipah glycoprotein, 3D11, were chosen and performed molecular docking to analyse the various conformations and interactions with the amino acids; further, their physicochemical and ADMET properties were also computed. The compound 5_Favipiravir have an excellent docking score (-6.16 kcal/mol), followed by compound 4_Favipiravir and 19_Favipiravir with docking score of -5.50 and -5.38 kcal/mol respectively. The three compounds had the respective heterocyclic moieties such as pyrazole, imidazole and pyrazinone. All the twenty-two designed compounds obey the Lipinski rule of five, which infer that they will not have problems with oral bioavailability. Thus, it is concluded that the incorporated heterocyclic groups in favipiravir can add to the anti-Nipah activity; hence it can act as future leads for the treatment for the disease caused by Nipah virus.

In Silico ADMET and Molecular Interaction Profiles of Phytochemicals from Medicinal Plants in Dakshina Kannada

“…26,27 With significant updates to functional modules, predictive models, explanations, and the user interface, ADMETlab 2.0 has a greater capacity to assist medicinal chemists in accelerating the drug research and development pro-cess. [28][29][30] The SMILES string of each compound was pasted separately and submitted. The evaluation results were then downloaded as a PDF file, and the scores were tabulated.…”

Are we ready to fight the Nipah virus pandemic? An overview of drug targets, current medications, and potential leads

“…Computational study related to favipiravir and its derivatives were also performed to check their effectiveness towards NiV-G protein [66]. Favipiravir shows a relatively good performance in the experimental work too [57].…”

“…The study indicated that piperazine-substituted favipiravir derivatives have a higher ability to bind than the original favipiravir structure. James et al studied 22 favipiravir derivatives by incorporating heterocyclic groups (moieties such as pyrazole, imidazole, and pyrazino) in favipiravir [66]. All derivatives were subjected to molecular docking for the Nipah G-protein (PDB ID:3D11) target followed by physical property evaluations and ADMET studies.…”