Computational approach to study the synthesis of noscapine and potential of stereoisomers against nsP3 protease of CHIKV

Prashant Singh; Durgesh Kumar; Vijay Kumar Vishvakarma; Parul Yadav; Abhilash Jayaraj; Kamlesh Kumari

doi:10.1016/j.heliyon.2019.e02795

Computational approach to study the synthesis of noscapine and potential of stereoisomers against nsP3 protease of CHIKV

Heliyon. 2019 Dec 24;5(12):e02795. doi: 10.1016/j.heliyon.2019.e02795. eCollection 2019 Dec.

Authors

Prashant Singh¹, Durgesh Kumar^{1

2}, Vijay Kumar Vishvakarma^{1

2}, Parul Yadav³, Abhilash Jayaraj⁴, Kamlesh Kumari⁵

Affiliations

¹ Department of Chemistry, A.R.S.D. College, University of Delhi, New Delhi, India.
² Department of Chemistry, University of Delhi, Delhi, India.
³ Department of Chemistry, National Institute of Technology, Rourkela, Odisha, India.
⁴ SCFBio, Indian Institute of Technology, Delhi, India.
⁵ Department of Zoology, DDU College, Delhi University, Delhi, India.

Abstract

Chikungunya fever is a major public health issue in India affecting millions of people and occurs due to Chikungunya. Chikungunya virus (CHIKV) is a single stranded RNA virus from the family of Togaviridae and genus alpha virus. It contain three structural proteins: glycosylated E1 and E2, embedded in the viral envelope, and a non-glycosylated nucleocapsid protein. Till date, researchers are working on inhibition of CHIKV but till now no cheap and effective medicine is available in the market. Therefore, the authors of this work thought of isoquinoline based noscapine to inhibit the nsP3 protease of CHIKV. The aim of the work is to understand the mechanism for the synthesis of noscapine theoretically using DFT. Further study the potential of all four isomers of noscapines {(13 (S,R), 14 (R,R), 15 (R,S) and 16 (S,S)} against nsP3 protease of CHIKV with the help of docking and MD simulation. The integrated e-pharmacophore binding affinity based virtual screening, docking and molecular dynamics simulation recognized four hits isomers as inhibition nsP3 protease of CHIKV. The docking energies of all the isomers of noscapine (13-16) with nsP3 protease CHIKV was found out to be more negative than baicalin (-8.06 kcal/mol) on selected sites. Amongst the isomers of noscapine, CMPD 13 possessed best binding affinity with four hydrogen bonding interactions. Further, ADME properties and blood-brain barrier permeability properties have been calculated. DFT studies of all the isomers of noscapine was investigated.

Keywords: Docking; MD simulations; MM-GBSA; Noscapine; Stereochemistry; Theoretical chemistry; Virtual screening; nsP3 protease of CHIKV.