Design and Identification of Lead Compounds Targeting Nipah G Attachment Glycoprotein by In Silico Approaches
Jainey P. James *
Department of Pharmaceutical Chemistry, Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Deralakatte, Mangaluru-575018, India.
. Apoorva
Department of Pharmaceutical Chemistry, Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Deralakatte, Mangaluru-575018, India.
Shreya Renita Monteiro
Department of Pharmaceutical Chemistry, Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Deralakatte, Mangaluru-575018, India.
K. B. Sukesh
Department of Pharmaceutical Chemistry, Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Deralakatte, Mangaluru-575018, India.
A. Varun
Department of Pharmaceutical Chemistry, Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Deralakatte, Mangaluru-575018, India.
*Author to whom correspondence should be addressed.
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.
Keywords: Nipah virus, Favipiravir, Molecular docking, Physicochemical & ADMET properties