USE OF MOLECULAR IMPRINTS OF MICROBIAL PROTEINS AS AN ALTERNATIVE TO ANTIBIOTICS FOR COMBATING THE THREAT OF ANTI MICROBIAL RESISTANCE (AMR)

Antimicrobial resistance or the increasing ability of pathogenic microbes to withstand and challenge antibiotic treatment is one of the major concerns faced by modern medical science. A lot of drug resistant strains of dangerous microbes that are called superbugs have emerged. Many of the viruses, bacteria, fungi and protozoa that were earlier susceptible to antibiotic treatments are becoming and more resistant now. Major cause of this increasing antimicrobial resistance is the uncontrolled availability and inappropriate usage of antibiotics, especially broad spectrum antibiotics even in minor and common infections. Widespread use of antiseptics in sanitation is also a reason. Antibiotics used in cattle and poultry industry as well as in agricultural products also play a role.

Reducing the usage of antibiotics as far as possible, as well as developing viable alternatives to antibiotics is an essential step in countering the threat of antimicrobial resistance. Use of phytochemicals and their derivatives is one alternative to antibiotics. But high levels of toxicity, as well as the chances of developing unwanted residual effects are some of the hindering facts.

Here I am proposing a new idea that may be used in developing alternatives to antibiotics for countering the threat of antimicrobial resistance.

All of us would have heard about molecular imprinted polymers. This is a new area of research in modern polymer chemistry. A molecularly imprinted polymer (MIP) is a polymer that has been processed using the molecular imprinting technique which leaves cavities in the polymer matrix with an affinity for a chosen “template” molecule. The process usually involves initiating the polymerization of monomers through host-guest interactions in the presence of a template molecule that is extracted afterwards, leaving behind complementary cavities. These molecular imprinted cavities in polymers will have conformational affinity for the original molecules that were used as templates, and are used in applications such as chemical separations, catalysis, or molecular sensors.

It is obvious that currently available molecular imprinted polymers cannot be used as therapeutic agents, as they are not at all bio-friendly. But what I am saying is, if we could find out some substances having polymer-like properties in their supra-molecular level nanostructures, developing of bio-friendly molecular imprinted drugs will be a clear possibility. Once we could find a way to prepare bio-friendly molecular imprints that can act as artificial binding sites for pathogenic molecules, a whole new range of molecular imprinted drugs will evolve. I think it is a new research area that has to be explored by scientific community involved in working upon innovative drug designing techniques.
Molecular imprints prepared by using microbial glycoproteins as templates can obviously act as antimicrobial agents, since they can bind to concerned microbial glycoproteins and inhibit their interactions with biological molecules. If these molecular imprints of microbial proteins are used instead of antibiotics and other chemical antimicrobial agents, chances of developing antibiotic resistance will not arise. Substituting antibiotics with molecular imprints of concerned microbial proteins will surely reduce the threat of antimicrobial resistance to a big extent.

The biggest challenge encountered in developing a protocol for preparing bio-friendly molecular imprinted drugs is to find out an appropriate material that could be used as imprinting matrix. Various biological polymers such as globulin proteins, carbohydrates, and nucleic acids are potential candidates. It was observed that concentrated solutions containing sucrose and fructose in water act as a good molecular imprinting medium. As far as our studies at ICLRMID (International Center for Learning and Research in Molecular Imprinted Drugs) has gone, water-ethanol mixture possess somewhat polymer-like properties at nanoscale supra-molecular levels, which could be utilized for preparing bio-friendly molecular imprints that could be used as therapeutic agents. Through a specially designed process involving the interaction between microbial glycoprotein protein molecules as templates and water-ethanol matrix as imprinting medium, we can produce hydrogen-bonded “host-guest complexes” wherein templates are “guests” and imprinting matrix is “hosts”. Removal of “guest” molecules from “host-guest” complexes were attained through a peculiar technique consisting of agitation, cavitation, nanobubble formation and precipitation. As the template molecules are removed by this process, supra-molecular networks of water-alcohol molecules carrying the three-dimensional imprints of templates in the form of nanocavities will remain. These nanocavities act as molecular imprints of glycoprotein molecules used as templates. These molecular imprints will act as Artificial Ligand Binds (MIALBS) for the specific glycoprotein molecules due to the conformational affinity between them. If we use viral glycoproteins or other essential microbial proteins as templates for this molecular imprinting protocol, the molecular imprints thus prepared can act almost similar to antibiotics.

I would appeal the scientific community to take this innovative humble idea of mine forward, and develop a whole new range of molecular imprinted drugs that can substitute antibiotics and other potentially dangerous drug substances currently used as therapeutic agents or prophylactics. By this technology, I hope we can produce a whole range of target-specific molecular imprinted drugs against almost any disease. It will obviously reduce the use of antibiotics, and it ultimately it will be a great step in combating the challenges posed by antimicrobial resistance.

Author: Chandran Nambiar K C

I started practicing homeopathy in 1970, when I was 20 years old and studying for final year of BSc (Zoology) course. My interest in homeopathy happened very accidentally, through a constant relationship with a local practitioner who happened to be father of my classmate. I was a regular visitor in his clinic, where from I started reading BOERICKE MATERIA MEDICA and other homeopathic books, which helped me to cure myself my troublesome asthma that have been haunting me since my childhood days. I became a voracious reader of homeopathy. I was also deeply involved in studying marxism and dialectical materialism during my college days, which attracted me to political activities. MARXISM and HOMEOPATHY became two essential parts of my intellectual and practical life, which still continues so. Even though I joined DHMS course in a karnataka homeopathic college, I could not continue it due to my intense involvement in revolutionary political activities that resulted in jail life and a lot of criminal cases. Once that phase was over, I took a diploma in veterinary science and became a livestock inspector in animal husbandry department under govt of kerala. I have been continuing my study and practice of homeopathy all through these years. Since CCH act came into force only in 1976, and it contained provisions allowing existing practitioners to continue, my homeopathic practice went smoothly in parallel with my government job. In 1987, co-operating with some local homeopaths and social activists, I started Kannur District Homeopathic Hospital Sociey, which established a chain of hospitals and homeopathic clinics in different parts of Kannur district. After a few years I had to leave the society for some political reasons, and I established a 100 bedded well equipped homeopathic hospital in Taliparamba, employing a number of prominent homeopaths. That was ended up as a financial disaster for me due to many reasons, including my lack of skills as a money manager, and I was compelled to close down my dream project with in a short period. I lost huge money I invested, lost my reputation, and it pulled me into a debt trap. I learned a lot of valuabl lessons from this failure- about life, human psychology, relationships, and above all, about myself. I realized failure is the greatest teacher, if you are prepared learn from it. I learned how will power and determination to win will help us come back into life as a phoenix from our own ashes. I learned, one does not fail unless he stops fighting and accepts failure. My failure and the hardships that followed has moulded my personality in such a way that I can now withstand any disaster and fight back. I tell you, you will not know what life really is, unless you miserably fail at least once in your life. By this time, I left my government job also, and settled as a full time homeopathic practitioner. By this practice, I could repair my earlier financial losses, and establish well in life. It was during this period that I felt the need of developing a simple and user-friendly homeopathic software, that resulted in the evolution of SIMILIMUM, which was later upgraded into SIMILIMUM ULTRA. Similimum Ultra was well accepted by the profession, and it collected good revenues which continues even today. I stopped my practice a few years back , and concentrated in the study and research activities to evolve scientifically viable explanations to the so-called riddles of homeopathy. This unrelenting study resulted in MIT or Molecular Imprints Therapeutics, which provides a scientific and rational explanation for homeopathy. I started a homeopathic discussion group on facebook called HOMEOPATHY FOR TOTAL CURE, which has more than 35000 homeopaths as members. By this work on facebook, I could establish close relationship with many homeopaths around the world. It goes on. I could successfully convert facebook as my office and work place, from where I propagate my MIT ideas, co-ordinate my works for homeopathic community, and sell my Similimum Ultra Software. My years of hardwork in search of HOW HOMEOPATHY WORKS ultimately resulted in the publication of a book titled REDEFINING HOMEOPATHY (3000 pages, 3 volumes, hard bound, Rs 6000), in which I have compiled my articles regarding my scientific explanations of basic principles of homeopathy. These ideas are called MIT or MOLECULAR IMPRINTS THERAPEUTICS. MIT is now included in the syllabus of MD (HOM) course of prestigious DY PATIL DEEMED UNIVERSITY, PUNE, INDIA. Research department of SARADA KRISHNA HOMEOPATHIC COLLEGE, Kulashekharam, Tamilnadu, India, the only NAC accredited homeopathy college in India, has recently taken up certain reserch projects for proving the scientific explanations proposed by MIT. Based on MIT perspective of homeopathy, I had developed an MIT PROTOCOL for scientific homeopathy, and initiated a project for establishing a chain of MIT NETWORK CLINICS all over India, where MIT PROTOCOL will be practiced. More over, I have developed a whole range of 351 MIT FORMULATIONS, which are disease-specific combinations of post-avogadro diluted homeopathy drugs. NOW I AM IN 71st YEAR OF MY LIFE, AND STILL LOOKING FOR NEW HORRIZONS!

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