Researchers looked at secretions from the skin of a south Indian frog called Hydrophylax bahuvistara and found it contained a peptide which could kill certain flu viruses in the lab. They called this peptide “urumin” – after a curved sword that comes from the same region of India as the frog.
They also found that urumin was able to protect mice from the flu virus. Only 3 in 10 mice given urumin died from the infection, compared to 8 in 10 mice which weren’t treated with urumin.
Research into urumin is still at an early stage, too early to say that this is a “cure” for flu. While it was effective against several types of flu virus in the lab – including the one that caused the 2009 swine flu pandemic – it didn’t work against others.
Still, despite these limitations, this is welcome news. Current antivirals have proved to have limited effectiveness against flu, and there is always the concern that a new flu pandemic could emerge.
Researchers are likely to continue to study urumin and make sure it is effective and safe enough to be tested in humans.
There were suggestions in the media that the urumin peptide could be a possible “cure” for flu. This suggestion is probably unwarranted given that we already know it does not kill all strains of flu.
Flu virus has many different varieties, and the peptide seemed good at killing one particular sub-type of influenza A called H1N1 (which includes strains such as swine flu, and the infamous Spanish flu of 1918-19), but not other sub-types, such as H3N2 (which is another common cause of seasonal flu).
The body can break down peptides like the one tested in this study, so researchers will need to find a way to stop this happening.
This was a study carried out by researchers from Emory University and the Icahn School of Medicine at Mount Sinai in the US, and the Rajiv Gandhi Center for Biotechnology in India. The laboratory and animal research looked for new antiviral molecules in the skin secretions of a south Indian frog.
Frogs are known to secrete substances from their skin that protect them from bacteria and viruses. These substances – called peptides – can also destroy some human viruses in the lab. The researchers in the current study wanted to see if any of the peptides could destroy the human flu virus.
This type of research is useful for identifying new substances that might be effective as human medicines.
When these potential new drugs are found, they then need to go through a long period of testing to ensure they are safe and effective enough before they can be tested on humans. Once they reach this stage they have to go through clinical trials to confirm their safety and how well they work before they can be used more widely.
The researchers collected skin secretions from Hydrophylax bahuvistara, a type of south Indian frog, and then returned them to the wild unharmed. They analysed these secretions to identify the peptides (small chains of amino acids) they contained.
They then tested each peptide to see if it could kill the human flu virus in the lab. They also tested whether the peptide harmed human cells in the lab to make sure it was not toxic to human cells.
Once they identified a suitable peptide they tested whether it could treat live mice which had been infected with a large dose of the flu virus.
They gave one group of mice a dose of urumin and another group an inactive control liquid into their nasal passages five minutes before infecting them with the flu virus. They then gave them urumin or control daily for the next three days and compared how the infection affected the mice’s weight (as ill mice lose weight), how many mice died, and how much flu virus was present in their lungs.
The researchers identified 32 peptides in the mucus collected from the frogs' skin. They identified four peptides which could kill more than half of a sample of the human H1N1 flu virus in the lab.
They selected the peptide which was least harmful to human cells in the lab for further study, and they named it “urumin”.
They found that urumin was effective at killing different types of H1N1 flu viruses in the lab – including the type which caused the 2009 swine flu pandemic. Urumin killed at least 60% of each of the eight types of H1N1 tested. It was also good at killing seven strains of H1N1 that were resistant to antiviral medicines such as Tamiflu.
The researchers found that urumin did this by targeting the part of the virus’s structure that is shared across different “H1” strains, called the “stalk region”. However, urumin was not as good at killing a different strain of flu (H3N2), where it killed less than half of the four samples tested.
Urumin protected live mice against the flu virus. Infected mice treated with urumin lost less weight and had less flu virus in their lungs. Urumin also reduced deaths; 70% of the mice treated with urumin survived compared to only 20% of those given the inactive control.
The researchers found that urumin did not have an effect on the other human viruses they studied.
Researchers often turn to natural substances with known health-giving properties to find potential new drugs for humans. For example, aspirin was developed based on a compound found in willow bark – which had been used in traditional medicine for hundreds of years.
Some other drugs – such as some chemotherapy and anticlotting drugs – have also been developed from chemicals found in plants.
By isolating the substances that have an effect the researchers can make sure they are pure and adapt and them to make them as safe and effective as possible for human use. This is another example of this process, using an animal’s natural defences to identify substances that could help protect humans.
It also offers yet another compelling reason why we should make an effort to prevent different species, both animal and plants, from becoming extinct. Potential treatments for human disease could be lost forever if a species disappears.
As yet, tests on urumin are in the early stages. So far it has only been shown to be effective at killing some types of flu viruses in the lab but not others, and researchers will want to test it against a wider range of flu viruses.
The path to developing new drugs is long, and it will be a while before we know if urumin is suitable for testing in humans, and whether it will be successful in these tests.
Flu viruses are hard to combat, because they mutate and change so rapidly. Therefore it is important the researchers continue to do studies such as this, to look for ways that they can be treated.
Holthausen, David J. et al. An Amphibian Host Defense Peptide Is Virucidal for Human H1 Hemagglutinin-Bearing Influenza Viruses Immunity , Volume 46 , Issue 4 , 587 - 595
Image: Anna Tanczos, Wellcome Images