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THE BATTLE WITH HIV

Down but not out?

Jayalakshmi K/DHNS

Amidst news that the HIV virus may be weakening, come reports of anti-viral activity of compounds derived from natural sources.

In a bid to survive and live longer, the HIV virus may have blunted its claw and decided to live amicably with its host, if one is to go by a recent study.

Reported in the journal AIDS, researchers from Case Western Reserve University in Cleveland and the Institute of Tropical Medicine in Antwerp compared genetically matching HIV samples from across a time span of 15 years and found that the virus had weakened. The virus potentially could stop causing disease within 60 years, they concluded.

Around 12 samples were taken from 1986-89 and studied with recent samples. Taken in petri dishes the samples replicated in the natural medium of white blood cells. Seventy-five percent of recent samples were found to be weaker on all counts.

What this means is that its capacity to reproduce inside the host has declined and consequently its ability to spread and infect. Such weakening trends have been shown earlier by the smallpox and syphillis virus.

Even if the study saw a weakening of the pathogen, there has been no evidence of a worldwide weakening. The time span is also being viewed cynically by some as too short a period for an aggressive and lethal microbe to have been tamed. Just because it does not spread does not mean it is any less dangerous, they warn. The pathogen that leads to AIDS still remains an aggressive and lethal microbe. It is a known fact that drug-resistant strains of HIV exist and are very lethal. The results on such a small sample cannot be regarded as definitive.

40 million infected

According to WHO almost 40 million people are infected with HIV globally and three million people died last year alone. In Asia alone some 1.2 million were infected in 2004.

One can take some hope from the study but not drop guard at any cost. The search for a drug against HIV has been gathering impetus and this is no time to get complacent. While most of the available drugs are costly and out of reach for many in developing nations, the good news is that work is progressing at a fast pace and India is not lagging. The focus here among other things is on developing anti-HIV agents from natural sources. Some of these are in the phase-II stage of clinical testing, according to a recent review that appeared in Current Science dated 25 July 2005. Basically how one gets infected is this: The HIV virus binds itself to the host cell at the CD4 receptor site found in the surface of lymphocytes (part of immune system). Studies have shown that a co-receptor is required to allow the HIV virus into the cell. Once in, the genetic material of the virus, its RNA undergoes reverse transcription into DNA. The process if facilitated by an enzyme in HIV called reverse transcriptase. Once the conversion is over the DNA integrates with the host genetic material in the cell nucleus and can stay there for years before becoming infectious.

The anti-HIV activity of many of the natural products work in various ways. Some inhibit the reverse transcriptase, some inhibit cell fusion, some prevent HIV replication. These could be extracts from root tubers, or alkaloids from leaves of plants, or fruits and twigs. A Malaysian company Sarawak already has the license to the calanolide class of compounds found to inhibit reverse transcriptase. The drug is in the phase II trail stage. Looking at the oxidative stress aspect of HIV flavanoids have proven to be good antioxidant agents with strong anti-viral activity in cell cultures and animal models. So also lignans. These are all isolated from plants such as Eucalyptus and the fruit rind of Terminalia bellerica, used commonly in Indian traditional medicine.

Plant compounds like tannins act by attaching to the proteins of the virus and reducing the viral adsorption, in short weakening its potency. Yellow pigments from the cotton plant have this property.

Quinones

Quinones show anti-HIV activity by acting in the last phase of viral replication cycle. Even carbohydrates from natural sources seem to have some potential by binding to the HIV protein. Marine organisms and microbes also are good sources of anti-HIV agents. By inhibiting the Tat protein of HIV required for replication and progression of the disease, ketones from microbes offer hope. Bovine milk contains proteins that inhibit the HIV transcriptase to various degrees. So also antifungal proteins found in legumes like mung bean, peanuts, cowpea, french bean. Lysozyme, a potent Aids-fighting protein is found in tears, saliva and the urine of pregnant women! It breaks done the virus working with another protein ribonuclease found in urine.

The good thing about these compounds are that they are mostly non-toxic and have specific activity, ruling out side effects. But more conclusive work alone will see how many of them reach the drug stage. As of now only three molecules have completed preclinical studies.