October 13, 2010
School of Engineering, Coimbatore
An Amrita research paper titled Homology Modeling and Protein Ligand Interaction to Identify Potential Inhibitor for E1 Protein of Chikungunya was recently published in the international journal Information and Communication Technologies – Communications in Computer and Information Sciences (Springer).
This paper by the Computational Chemistry Group at Amrita’s Coimbatore campus highlighted the findings of the research team with regard to inhibiting Chikungunya using medicinal plants.
An overwhelming, but non-fatal viral illness that has recently seen an outbreak in many parts of India, Chikungunya remains a challenge for the medical community. Although several drugs are available to counteract the disease, none are fully effective and all have undesirable side effects.
“Our country is blessed with medicinal plants,” explained Dr. Krishnan Namboori, who led the study. “It was in these plants that our research team sought their answers.”
The research team focused on identifying and developing effective potential drug molecules to counteract Chikungunya. The team studied the characteristics of the Chikungunya virus, its structure and its response to various chemicals and phytochemicals from medicinal plants.
“This was done to gain an insight into a suitable inhibitor for the Chikungunya E1 envelope protein that would prevent binding of the virus with the host cells,” further explained Dr. Namboori.
“Arthropod-borne viruses (arboviruses) are the causative agents of most of the budding infectious diseases and are reasons for major public health concerns.”
The team successfully identified inhibitory activity of nine phytochemicals as a result of interaction studies carried out between various phytochemicals and the target proteins.
Of the nine phytochemicals, a promising inhibitor, Osltamivir, was identified. The team found that this could potentially stop the binding of the Q1El92_CHIKV virus with the host.
Further clinical analysis is required before the compound can be used on a commercial scale.
“It was interpreted that Osltamivir could be a promising inhibitor for E1 domain of Q1El92_CHIKV virus as the drug target yet pharmacological studies have to confirm it,” summed up the paper abstract.
In addition to research associates of the Computational Chemistry group, participants in the research study included M.Sc. (Bioinformatics) graduates from the Amritapuri campus as well as final-year M.Tech. (Biomedical Engineering) students from Coimbatore campus.
PAPER DETAILS
C. S. Vasavi, Saptharshi, R. Radhika Devi, Lakshmi Anand, Megha. P. Varma and P. K. Krishnan Namboori, Homology Modeling and Protein Ligand Interaction to Identify Potential Inhibitor for E1 Protein of Chikungunya
Abstract
Chikungunya fever is an overwhelming, but non-fatal viral illness that has been reported in many parts of the country. The E1 domain of Q1El92_CHIKV virus that helps in binding with the host has been determined by using comparative homology modeling program MODELLER based on crystal structure of the homotrimer of fusion glycoprotein E1 from Semliki Forest virus as a template protein and it had 63% sequence identity. The modeled structure‘s energy was minimized and validated using structure validation server in which 82.8% of the residues were present in the most favored regions of the Ramachandran plot. Disulphide bonds which help in protein folding of the proteins were analyzed and it was found to be conserved for both the homologous and the modeled structures. The ion pairs which contribute to fusion of viral membranes and that help in solvent protein interactions were analyzed. Docking studies was carried out with various phytochemicals and it was found that osltamivir had the most stable interaction with the E1 domain of the Q1El92_CHIKV virus. Thus from the complex scoring and binding ability it was interpreted that Osltamivir could be a promising inhibitor for E1 domain of Q1El92_CHIKV virus as the drug target yet pharmacological studies have to confirm it.
