Can a scorpion’s sting destroy superbugs — the multidrug-resistant microorganisms (MDRO) that completely defy antibiotics?
WHO estimates that MDROs account for 700,000 deaths every year. It is the frequent overuse of antibiotics that has led to the evolution of superbugs. In its 2020 report, the Indian Council of Medical Research (ICMR) categorised pathogens causing serious infections into three groups based on their drug resistance capacity. The group 1 pathogens were resistant even to antibiotics used as a last resort.
Researchers at the Department of Biophysics, Panjab University, Chandigarh — in collaboration with the Department of Materials Science and Engineering, Yonsei University, South Korea — have been working with an antimicrobial peptide (AMP) found in scorpion venom that is seen effective against viruses, bacteria, parasites, and cancer cells.
AMPs are emerging as promising alternatives to antibiotics. (Peptides, like proteins, are chains of amino acids, only much shorter.)
Positively charged, AMPs act as the first line of defence against microorganisms in most living beings. While antibiotics act against pathogenic microorganisms with the help of the body’s innate immune system, AMPs kill microbes by targeting their plasma membrane, metabolic sites, and/or intracellular sites.
“To fight superbugs, AMPs either bind to the negatively charged plasma membrane (outer layer) of the microbes via electrostatic attraction or inhibit the intercellular processes (DNA, RNA and protein synthesis), eventually killing the microbes,” says Dr Ravi Pratap Barnwal, who heads the Punjab University research team.
Modern researchers have been looking at stabilised alpha-helical peptides (the alpha helix is a common pattern in the secondary structure of amino acids) as next-generation therapeutics. But such peptides were found to have limited functionality and stability due to their small size.
The Indo-Korean research has, on the other hand, focused on alpha-helical ligands (any molecule or atom that irreversibly binds to a receptor molecule) based on proteins that can make “steric clashes” with targets due to their large size. Notes Dr Barnwal, “Peptide-based alpha-helical ligands are good drug candidates for the regulation of biomolecular interactions due to their structural compactivity and design. Our current work involves developing a system where a pseudo-isolated alpha helix can exist in a monomeric (stable) state.
“This alpha helix can efficiently interact with deep and narrow targets from different pathogens (HIV, SARS-COV) and other diseases.”
The alpha helix ligands designed in this system do not require chemical modifications, have high thermal stability, and make favourable interactions just like isolated peptides.
“These peptides have the potential to replace conventional treatment approaches that involve antibiotics,” he adds.
But how did they zero in on scorpion venom? “The idea was inspired by the MP-1 peptide obtained from the venom of the Brazilian wasp. Venoms are a rich source of antimicrobial peptides.”
The AMPs in scorpion venom can enter microbial membranes by creating pores, and serve as antibiotic to help scorpions clean the biological conduits that carry venom to their stingers. Apart from anti-bacterial activity, scorpion AMPs have also been found to possess anti-viral, anti-cancer, anti-fungal, and anti-parasitic properties. The low toxicity of scorpion AMP also made it an ideal candidate for research, says Dr Gurpal Singh, another lead research member on the Indian side.
The research team for the antimicrobial peptide work included Dr Barnwal, Akshita Thakur, Akanksha Sharma, Dr Hema K Alajangi, and Dr Gurpal Singh (all from Panjab University), and Prof Yong-beom Lim and his team from Yonsei University. While for the alpha-helical peptides work, the team included Dr Barnwal, Mandeep Kaur, and Prof Lim and his team.
Dr Barnwal has so far not been contacted by any pharmaceutical company for AMP/helical ligand in India. But Prof Lim is in talks with some pharma companies for product development in South Korea.
September 18, 2022