Roorkee: Indian Institute of Technology Roorkee Researchers have identified a molecule that exhibits antiviral activity against Chikungunya virus. The antiviral activity achieved around 99 per cent reduction in the virus. At present, there are no drugs or vaccine available in the market to treat Chikungunya disease.
The Research Team led by Prof Shailly Tomar, Department of Biotechnology, IIT Roorkee, used structure-based studies of Chikungunya virus specific nsP2 protease to identify molecules — Pep-I and Pep-II — that exhibited protease inhibitory as well as antiviral activity.
Speaking about the importance of this Research, Prof. Shailly Tomar said, “The nsP2 protease is a strict viral enzyme. Means it is absent in humans, and thus, is an excellent antiviral drug target for chikungunya virus. Our research group has targeted nsP2 using biochemical and structure-based approach. We identified a molecule that not only possesses anti-nsP2 activity but also effectively kills the chikungunya virus in the cell based assays.”
The Research was funded by the grant from the Department of Biotechnology (DBT) and published recently in the Elsevier journal ‘Biochimie DOI:10.1016/j.biochi.2018.04.004
One of the two molecules — Pep-I — has higher antiviral activity against chikungunya virus. The PeP-I molecule inhibits the enzymatic activity of nsP2 viral protein and in cell based assay proves to be an effective antiviral molecule.
Speaking about the future work that is going to be done in this direction, Prof Shailly Tomar said, “Derivatives of PeP-I and PeP-I like molecules are being developed that will be tested for their antiviral potential in animal model”
According to the researchers, any molecule that inhibits nsP2 protease should possess antiviral activity. To test the hypothesis they carried out antiviral studies using cell lines. The Pep-II molecule showed reduced antiviral activity of only 50% even at a higher concentration of about 200 microMolar. The antiviral activity was tested by adding the molecules directly into the virus culture. The two molecules also reduced the viral RNA thus confirming the antiviral activity.
According to Mr. Rajat Mudgal, the research scholar from the Department of Biotechnology, IIT Roorkee, and one of the first authors of the paper, “Out of the two molecules, PeP-I is more effective as an antiviral molecule as no virus was detected in cultured cells at concentration as low as 10 mM. ”
According to Mr. Harvijay Singh, the research scholar from the Department of Biotechnology, IIT Roorkee, the other first author of the paper, “We developed a high throughput FRET based nsP2 protease assay and inhibitory activity of the two molecules PeP-I and Pep-II was confirmed using this biochemical assay”