Why going back to the roots of medicine in nature could help fill the drug discovery gap
While humans evolved over a period of approximately 6 million yearsbreakthroughs in modern medicine as we know it today only began in 19th and 20th centuries. So how did humans manage to survive millions of years of sickness and disease without modern drugs and treatments?
This is a question I asked myself when the COVID-19 pandemic hit my family in India in April 2020, when access to vaccines and treatment was very limited. All my years of working like biomedical scientist, requiring empirical evidence and formal safety testing before using any treatment, took a back seat as I rushed to potential therapies from every source I could find, whether scientific or folklore articles. I was ready to try any experimental or traditional medicine that might have a chance of helping my father.
Fortunately, my father recovered. I can’t say for sure if any of the traditional medicines we used actually helped him recover. But as someone whose entire scientific career has been focused on discovering new drugs from chemical compounds found in nature, I wondered if there was a molecule in the traditional drugs we used that might be isolated and optimized to treat COVID-19.
Scientists like me have searched for new drugs for various diseases by purifying compounds that exist in nature instead of synthesizing new ones in the lab. Of COVID-19[feminine] at antibiotic resistanceI believe that past successes and new technologies show the enormous potential for developing new drugs from natural products.
The advantage of the natural product
Humans have co-evolved with the rest of nature over time, and obtaining medicine is perhaps one of the most important interactions people continue to have with the natural world. DNA analyzes have shown that early humans may have treated abscessed teeth with poplar, containing the active principle of aspirin, and Penicillium mold, containing the antibiotic penicillin.
Researchers call molecules like those that give poplar and Penicillium their biological effects natural products because they are produced by living organisms such as microbes, fungi, corals and plants. These natural products have evolved to become structurally “optimized“to perform particular biological functions, primarily to deter predators or gain a survival advantage in a particular environment and relative to other competitors.
Since natural products are already designed to work in living things, this makes them particularly attractive as a source of drug discovery. While proteins may look different in different organisms, many have similar structural features and functions across species. This may help facilitate the search for related proteins that work in humans.
Natural Products Hall of Fame
Natural products derived from microbes and plants are the greatest resource for drug discovery for modern medicine. For example, the discovery of the antibiotic penicillin in 1940 from Penicillium mold allowed doctors to treat previously deadly infections and started the era of antibiotics.
Since September 2019, more than 50% FDA-approved drugs currently available are directly or indirectly derived from natural products. One of the best-selling drugs of the past two decades, the cholesterol-lowering drug atorvastatin (Lipitor) is derived from a compound produced by the fungus Penicillium citrinum. From 1992 to 2017, sales of atorvastatin in the United States totaled US$94.67 billion.
Penicillin revolutionized medicine.
Other prominent examples of natural product-derived drugs currently in use today include the antifungal amphotericin Bisolated from soil bacteria Streptomyces nodosuschemotherapy taxolisolated from the bark of the Pacific yew, and the immunosuppressant cyclosporinefungus isolated Tolypocladium inflatum.
I believe that undiscovered treatments for a wide range of diseases lie right under our noses in natural products. In January 2021, the FDA approved voclosporin (Lupkynis)fungus isolated Tolypocladium inflatum, to treat lupus. Recently, researchers have focused on cannabidiol and other cannabinoid compounds as a potential way to prevent or treat COVID-19. The FDA has not yet authorized any CBD-containing drugs for COVID-19.
The Challenges of Natural Product Discovery
Researchers are increasingly able to use new screening technologies and methods to isolate hitherto unidentified natural products. Screening for natural products usually involves browsing through an extensive library of extracts from natural sources. The Natural Products Drug Discovery Corewhich I co-founded with my colleague David Sherman at the University of Michigan, for example, searches for potential drug targets in a library containing approximately 50,000 natural product extracts each containing 30 to 50 molecules to be tested.
However, drug discovery using natural products is not without its challenges. Since the 1980s, natural products have fallen out of favor due to a number of challenges. These include the difficulty of accessing expensive screening methods and the limitations of technology that is unable to fully analyze the complexity of natural products. There is also ecological and legal considerations, such as sustainable access to samples and the maintenance of biodiversity. Pharmaceutical companies have reduced their natural product drug discovery programsand federal funding is also in short supply due to limited profitability.
Finding new drugs in nature
New drugs are often needed for unprecedented health emergencies like COVID-19. They are also needed for a health emergency that began long before the pandemic – antibiotic resistance.
A September 2017 Report of the World Health Organization has reaffirmed that antibiotic resistance is a global health emergency that will seriously compromise the progress of modern medicine. If current antibiotics lose their effectiveness, common medical procedures like C-sections and cancer treatments can get incredibly risky. Transplantation could become virtually impossible. Antibiotic-resistant microbes were the direct cause of approximately 1.27 million deaths in 2019. Treating just six of the 18 microbes that pose a threat to antibiotic resistance would be expensive more than $4.6 billion per year in the United States only. The The COVID-19 pandemic has reversed earlier progress in addressing this issuewith a 15% increase in antimicrobial resistant infections from 2019 to 2020. In contrast, antimicrobial resistant infections had fallen by 27% from 2012 to 2017. Among the probable causes of this decline was the increase in the use of antibiotics, difficulty following infection control guidelines and longer hospital stays.
According to recent estimates, about 75% approved antibiotics are derived from natural products. There are thousands of microorganisms in the ocean remains to be explored as potential sources of drug candidates, let alone all those on earth. In the search for new drugs to combat antibiotic resistance, natural products may yet be the way forward.
on pharmaceuticals and drug manufacturing: