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Published on: July 15, 2019
Cyclophilin A: a possible host modulator in Chandipura virus infection
Daya V Pavitrakar1, Nitin M Atre1, Anuradha S Tripathy1
1ICMR-National Institute of Virology, 130/1 Sus Road, Pashan, Pune, 411021, India.
Insights
Chandipura virus (CHPV) causes severe pediatric encephalitis. Inhibiting cyclophilin A (CypA) with cyclosporin A significantly reduced CHPV replication, suggesting CypA as a therapeutic target for CHPV infection.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Chandipura virus (CHPV) is a significant cause of pediatric encephalitis in India with high mortality.
- No vaccines or therapeutics are currently available for CHPV infection, necessitating novel treatment strategies.
Purpose of the Study:
- To investigate the potential of targeting host proteins for CHPV antiviral therapy.
- To evaluate the effect of inhibiting cyclophilin A (CypA) on CHPV replication.
Main Methods:
- In vitro inhibition of CypA using cyclosporin A.
- Quantification of CHPV titer and CypA levels.
- In silico molecular docking and dynamics simulations of CHPV nucleoprotein and human CypA interaction.
Main Results:
- Cyclosporin A treatment resulted in a 3-log reduction in CHPV titer.
- CypA levels were undetectable after treatment.
- In silico analysis confirmed stable interactions between CHPV nucleoprotein and human CypA.
Conclusions:
- Cyclophilin A plays a role in facilitating CHPV replication.
- CypA is a potential host factor for future antiviral drug development against CHPV.
Abstract:
Chandipura virus (CHPV), belonging to the genus Vesiculovirus of the family Rhabdoviridae, has been identified as one of the causes of pediatric encephalitis in India. Currently, neither vaccines nor therapeutic drugs are available against this agent. Considering that the disease progresses very fast with a high mortality rate, working towards the development of potential therapeutics against it will have a public health impact. Although the use of viral inhibitors as antiviral agents is the most common way to curb virus replication, the mutation-prone nature of viruses results in the development of resistance to antiviral agents. The recent development of proteomic platforms for analysis of purified viral agents has allowed certain upregulated host proteins that are involved in the morphogenesis and replication of viruses to be identified. Thus, the alternative approach of inhibition of host proteins involved in the regulation of virus replication could be explored for their therapeutic effectiveness. In the current study, we have evaluated the effect of inhibition of cyclophilin A (CypA), an immunophilin with peptidyl-prolyl cis/trans-isomerase activity, on the replication of CHPV. Treatment with cyclosporin A, used in vitro for the inhibition of CypA, resulted in a 3-log reduction in CHPV titer and an undetectable level of CypA in comparison to an untreated control. An in silico analysis of the interaction of the CHPV nucleoprotein with the human CypA protein showed stable interaction in molecular docking and molecular dynamics simulations. Overall, the results of this study suggest a possible role of CypA in facilitating CHPV replication, thus making it one of the potential host factors to be explored in future antiviral studies.
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