A Theoretical Model to Study the Interaction of Erythro‐Noscapines with nsP3 protease of Chikungunya Virus

Abstract

For the better management and control of the viral replication, it is essential to discover a potential molecule to combat Chikungunya virus (CHIKV). The work aims to find a potential antiviral molecule via its interactions with the non-structural protease (nsP3) of CHIKV. It plays a crucial role in intracellular replication. The best molecular interaction is based on the minimum total binding energy of hydrogen bonding, electrostatic interaction and van der Waals forces. It was found that Erythro-noscapines showed good binding affinity with nsP3 protease of CHIKV (PDB ID: 3GPO) and minimum total binding energy (-149.964 kcal/mol) to form a more stable complex i. e. 109-nsP3 protease of CHIKV. Erythro-noscapines (109, one of the derivatives of erythro-noscapine) showed better interaction than the reported molecules by different reseach groups via docking. The parameters for bioactivity score and Lipinski "Rule of Five" were calculated to estimate the pharmacokinetic properties of antiviral Erythro-noscapines and compared to others. 109 can be considered as a good candidate for antiviral replication against nsP3 protease of CHIKV. Molecular dynamics simulations on nsP3 protease of CHIKV with or without 109 was performed and studied. Further, binding free energies of potential noscapine-nsP3 protease of CHIKV based on Molecular Mechanics-Generalized Born Suface Area (MM-GBSA) was calculated. Further, toxicity of top 10 noscapines and reported molecules by different research groups was determined and then, density functional theory was applied to understand the singlet and triplet states of the 109.

Selective Docking of Pyranooxazoles Against nsP2 of CHIKV Eluted Through Isothermally and Non‐Isothermally MD simulations

“…Based on biological activity value filtration was done and CMPD167 was selected for molecular docking in each drug sites and MD simulations …”

“…Researchers showed their interest in the finding of the small molecules targeting the nsP2. Previously, the research group has developed a theoretical model against the nsP3 protease of CHIKV . In the present study, develop a theoretical model to find potential candidate for the inhibition of nsP2 of CHIKV.…”

A Theoretical Model to Study the Interactions of Xanthene-1,2, 3-Triazolyl-N-Riboside and Xanthene-Piperidinyl-Benzisoxazole Based Conjugates With the Insulin: Design, Docking and ADME Studies

“…This binding is obtained by the electrostatic and van der Waals interaction along with the hydrogen bonding. Further, the molecular interactions of best five compounds with insulin at residues level were studied [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47].…”

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

“…Current therapies for CHIKV-infected patients with arthritis/arthralgia mainly involve management of pain and inflammation using non-steroid anti-inflammatory drugs (NSAIDs), as well with fluid intake to prevent dehydration. There is no licensed antivirals or vaccines available for CHIKF, therefore, there is a vital need for the development of novel and potent drugs against CHIKV [9,10,11]. Noscapine is benzylisoquinoline alkaloid belongs to plant family poppy.…”