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Kokum to the rescue


A molecule in the popular spice can help prevent the spread of the AIDS virus in the human body.
The fight against the deadly human immuno deficiency virus (HIV) is all set to get a desi flavour. Indian researchers have isolated a compound from kokum  a berry widely used as a flavouring agent in Goan cuisine ” that has a remarkable anti-HIV potential. But the compound may have to cross several hurdles before it becomes a potent weapon in the war against AIDS, an epidemic that has already killed millions and may kill several millions more in the near future.

Tapas Kundu and his team at Bangalores Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) knew for at least three years that the rind of kokum (Garcinia indica, a plant indigenous to the Western Ghats) contains a wonder molecule called garcinol. Kokum is also used as a substitute for tamarind in Konkani cuisine and select dishes in Maharashtra, Gujarat and Kerala. In addition to garnishing curries and soups, it is used for its astringent, cardio-tonic, anti-allergic and digestive properties. Kokum seeds yield a unique fat that is used in making ointments, suppositories, lipsticks and chocolates.

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In 2004, Kundu’s team showed for the first time that garcinol has a unique property of impeding a human enzyme that, incidentally, is marshalled by the HIV virus for its own proliferation in the human body. So if one has a compound that inhibits this protein, called p300, one can substantially curb the multiplication of the dreaded virus to such an extent that the human immune cells can take over from there. Garcinol does possess this capability, but there is one problem: it is toxic to normal human cells which in its presence die in a few hours.

It is here that Kundu’s grounding in biochemistry was of help. Kundu, who has a doctorate in biochemistry from the Indian Institute of Science, Bangalore, chemically tweaked garcinol to create what is known as isogarcinol. Further chemical modification yielded 50 different compounds and one of these   LTK-14   was found to spare human cells but block p300.

“What is remarkable about their work is that they modified this natural molecule in such a way that it has become cell friendly,  says Udaykumar Ranga, a molecular virologist at JNCASR who specialises in HIV. Besides, LTK-14   unlike its parent compound — has the ability to cross the cell membrane with ease, he observes.

According to Kundu, the newly derived molecule was found to reduce the viral load by up to 80 per cent in the infected cells. The work was recently reported in Chemistry & Biology.  We have found that the compound inhibits all p300-mediated gene expressions,  Kundu, who has a basic degree in agriculture from Bidhan Chandra Agricultural University in Nadia, told Know How.

However, Ranga  also a co-author of the paper   thinks it’s too early to be upbeat. The molecule’s action is radically different from that of existing drugs. While anti-viral medicines target the virus itself, this one is trying to destroy a molecule in human cells whose mechanism the virus hijacks to proliferate.  It’s quite like bombing a neighbourhood where enemies are holing up. The bomb has to be dropped in such a way that it kills the maximum number of enemies with bare minimum damage to others,” Ranga explains.

A histone acetyltransferase protein, p300 has several functions in cells. A molecular switch that turns on or off a number of genes inside the cell, it’s pivotal for several key functions such as cell growth, differentiation and its eventual death. “Living cells are remarkable. Our studies have shown that when p300 is absent, others within the cells take over and carry out these tasks,” Kundu observes. On the other hand, the prominent HIV protein — known as TAT — that ensures the virus’ multiplication in the human cells can do so only if p300 is available.

Developing drugs against viruses as wily as HIV is tricky. “They are like volcanoes,” says Ranga. “While some erupt and explode, others lay latent and wait for an opportune time. No weapon in our arsenal today is capable of tackling a dormant virus.

Source: The Telegraph (Kolkata, India)