New Method Identifies Venoms for Therapeutic Uses
Specific venoms may lead to targeted therapies for conditions such as multiple sclerosis, rheumatoid arthritis, and other inflammatory disorders.
Researchers in a recent study created a method to identify venoms that specifically target parts of the body in order to optimize the venoms for therapeutic use.
Potent molecules in venoms have the potential to be adapted into medications, but they are difficult to isolate and study using current methods.
The researchers created a new method that can be used to identify venoms that block a protein on T cells. This protein is related to multiple sclerosis, rheumatoid arthritis, and other inflammatory disorders, according to the study published in Angewandte Chemie International Edition.
The researchers were able to use their method to find a variant of a venom that blocks this protein, which resulted in reduced inflammation in mice.
"Until now, we haven't had a way to seriously harness venoms' vast therapeutic potential," said lead researcher Richard A. Lerner, MD.
A low dose of venom in the right place can be very beneficial. The drug ziconotide (Prialt) is a painkiller derived from the venom used by cone-snails to immobilize their prey. Venoms are also very potent and selective.
The method used is quick and extracts only the information from the venom. The researchers gathered data from animal toxin databases and created a list of 589 venoms. Researchers then synthesized the venoms’ genes and placed them inside of viruses that deliver the genes to the cells.
A common target of venoms is the potassium ion-channel protein Kv1.3, which facilitates the proliferation and migration of T cells that drive inflammatory disorders, according to the study.
The researchers were able to use a cell-based selection system to screen their data for venoms that block Kv1.3. Researchers then created a culture of Kv1.3-contaning test cells that would switch on a red florescence gene if there was a strong interaction between the cells and the venom.
Researchers were able to find 27 likely Kv1.3-blocking venoms through this selection process. They identified scorpion venom (CIITx1) as a potassium-channel blocker, as well as another venom only suspected to be a blocker. The other 25 venoms were already confirmed blockers.
This method could be useful for screening artificial variants (analogs) of venom to discover those with optimal pharmaceutical properties, according to the study.
Researchers generated approximately 1 million analogs of a protein based on a sea anemone toxin that blocks Kv1.3 (ShK). The analogs were put through 3 rounds of selection and resulted in the researchers choosing S1-2, which was able to block Kv1.3 and reduced inflammation in a rodent model.
"This analog appears to be very potent against Kv1.3 and has no off-target effects on closely related ion channels," said Hongkai Zhang, co-first author of the study.
Researchers plan to use this method to find more drug candidates using much larger datasets.
"We're particularly interested in finding venoms that block sodium ion channels involved in pain," Dr Lerner concluded.