The global wound care market is on the rise with exorbitant costs incurred each year for skin wound care. Nature-derived drugs with wound healing properties that can be manufactured at a lower cost are presently a global requirement. Now, a study by scientists at Tezpur University has identified the country’s first wound-healing peptide from snake venom with anti-bacterial, anti-inflammatory and non-enzymatic properties.
If you have not already seen one, then you would have surely heard of it as one of India’s big four snakes. Widely distributed throughout the country, the Russell’s viper is (in)famous for its blood-clotting venom and for causing the maximum number of deaths among the venomous snakes of India.
There is a silver lining to this cloud, however. A recent study led by Ashis K Mukherjee, Professor at Tezpur University, Assam, has identified a peptide in Russell’s viper venom that can heal skin wounds by inducing the formation of new blood vessels, a process known as angiogenesis.
The wound healing drug market today is dominated by concoctions of enzyme-based agents which cleanse the wound of foreign material and dead tissue for faster healing. Drugs that facilitate wound-healing through angiogenesis are almost non-existent.
“Unfortunately, the availability of drugs from natural sources capable of cutaneous (skin) wound repair is still limited, although it can occupy a huge global market,” says Mukherjee.
The Russell’s viper venom is a cocktail of toxic and non-toxic proteins. RVVAP (Russell’s Viper Venom pro-Angiogenic Peptide) is a low molecular mass, non-enzymatic peptide found in Russell’s viper venom. Small peptides are easily absorbed by the skin and are not recognised as foreign entities, thereby having little to no side-effects.
As part of an attempt to develop drugs from natural sources, Mukherjee’s team had purified RVVAP from crude Russell’s viper venom in 2014. Intrigued by the small size and pro-angiogenic properties of this peptide, the researchers explored its role in wound healing. They prepared cream-based formulations of purified RVVAP and applied them topically twice daily to skin wounds created in rats. Freshly prepared Aloe vera extract served as a positive control, due to its well-known wound-healing and anti-bacterial properties.
The researchers monitored the wounds for a week by outlining the area of wound closure on tracing paper. To examine the anti-bacterial properties of these formulations, they streaked swabs from the treated wounds onto agar plates and checked if there was a reduction in the number of surviving bacterial colonies. Anti-bacterial properties in wound-healing creams reduce the risk of secondary infections.
Although RVVAP independently showed wound-healing and anti-bacterial properties, the best results were obtained with a formulation combining RVVAP and Aloe vera. RVVAP also reduced inflammation from skin injuries. RVVAP-treated mice had normal physical, behavioural and blood parameters and the peptide was non-toxic and non-lethal at a low dose.
Kartik Sunagar, Assistant Professor at the Evolutionary Venomics Lab, Indian Institute of Science, Bangalore, who was not associated with this research considers this a well-planned, proof-of-concept study that has added to the domain of wound-healing drug discovery from bioresources. He believes that many such components can be promising, but a follow-up study like this is absolutely essential. He says, “Discovery of this peptide is in itself very interesting. This study emphasizes that more research needs to be done on venoms from a perspective of drug discovery in human therapeutics, especially by venom biologists in India.”
“In future, we are planning to work on two aspects: First, deduce the primary structure of RVVAP so that it can be chemically synthesized or cloned and manoeuvred for better wound healing activity. Second, understand its mechanism of action in the presence of Aloe vera which may help in developing RVVAP as a prototype for peptide-based wound healing therapeutic agent.” says Mukherjee. He adds that the fact that RVVAP is non-enzymatic could mean that it would have a longer shelf-life compared to enzyme-based agents in the market, if developed into a drug prototype.
RVVAP is the first peptide reported from Russell’s viper venom with these unique properties and a role in wound healing. Although there have been previous reports of snake venom peptides with wound healing potency, this is the first such report from India. This study potentiates the longstanding history of snake venoms in therapeutics and has opened up a new avenue in the underexplored domain of Russell’s viper venom peptides in wound healing.
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