A drug to treat chikungunya virus infection is in the offing, and in vitro studies carried out by a team of researchers from the Indian Institute of Technology (IIT) Roorkee show promise.
Currently, there is no cure for the disease and treatment is focused more on relieving the symptoms.
Since the team led by Prof. Shailly Tomar from the Department of Biotechnology at IIT Roorkee used an existing drug piperazine, safety of the drug is already known and hence the trials on animals and humans will be more to understand the efficacy of the drug in treating chikungunya infection.
Piperazine is used for the treatment of worm infections.
The antiviral drug indinavir used for treating HIV positive people is a piperazine-based molecule.
The derivatives of piperazine are used as anti-histamines and anti-depressants drugs too.
Based on crystal structure, the researchers ascertained that the drug molecule binds to the hydrophobic pocket of capsid protein of Aura virus.
Drug binding studies were also carried out using chikungunya virus and it was found that the binding of the drug at the caspid protein was better in the case of chikungunya virus.
The function of capsid protein is essential for the virus budding and replication of virus.
On studying the antiviral activity of piperazine molecule against chikungunya, it was found that the molecule inhibits virus replication.
In the presence of this drug, the amount of virus released by infected cells is less. The drug showed very good antiviral activity.
Chikungunya viral load reduces significantly when treated with 3 millimolar (mM) of piperazine and has “barely detectable cell toxicity” when the dosage is doubled to 6mM.
Compared with controls, the inhibition of the virus replication was nearly 98% when 6mM of the drug was used.
Once the drug binds to the target, the capsid protein’s interaction with the enveloped protein of virus is inhibited and hence the virus release from infected cells is affected.
Virus replication and budding are correlated. The monkey cell lines were infected with very low virus concentration and then allowed to grow.
After 24 hours, the number of virus being released by the infected cells was studied. If the virus is able to replicate then should find more virus, which was not the case.
The chikungunya viral load had reduced by 98% at the end of 24 hours but increases at 48 hours indicating that inhibition of virus replication becomes less at the end of 48 hours compared with 24 hours.
This could be because the drug does not kill all the virus at the end of 24 hours and the drug supplied initially is already bound to the capsid protein target in the virus.
So when the virus reinfects nearby cells and replicates, there is not enough drug to bind to the new capsid protein molecules being produced.
The researchers are planning to carry out trials on animals.
Since the drug is already approved for use in humans, toxicity studies in animals will not be needed. But studies on animals to evaluate the antiviral activity and, hence, the efficacy has to be carried out.