The surprising truth: Is ivermectin a natural product?

October 10, 2025 •

3 min read

First discovered from a microbe in a Japanese soil sample, the precursor to ivermectin is indeed a natural product. However, the final antiparasitic medication, ivermectin, is not purely natural but a semisynthetic derivative, created through a specific chemical modification process.

Quick Summary

Ivermectin is a semisynthetic antiparasitic agent, derived from the natural compound avermectin, which is produced via the fermentation of the soil bacterium Streptomyces avermitilis.

Key Points

Semisynthetic Origin: Ivermectin is not a natural product but a semisynthetic drug, created by chemically modifying a natural compound called avermectin.
Natural Precursor: The natural compound, avermectin, is produced by the soil-dwelling bacterium Streptomyces avermitilis, discovered in Japan.
Chemical Modification: The process involves a selective hydrogenation step to modify the avermectin structure and create ivermectin, enhancing its properties.
Nobel Prize Recognition: The discovery and development of avermectins and ivermectin earned Satoshi Ōmura and William Campbell the 2015 Nobel Prize in Medicine.
Distinct from Synthetic Drugs: As a semisynthetic, ivermectin occupies a middle ground, deriving from nature but requiring lab-based chemical synthesis, unlike purely synthetic drugs like aspirin.
Selective Mechanism: Ivermectin works by targeting specific glutamate-gated chloride ion channels found exclusively in parasites, explaining its safety profile in mammals.

The natural origin of avermectin

The journey of ivermectin begins with a remarkable discovery in the natural world. In the late 1970s, a team led by Japanese microbiologist Satoshi Ōmura at the Kitasato Institute isolated a new strain of bacteria from a soil sample found near a golf course in Japan. This microbe, named Streptomyces avermitilis, was found to produce a powerful new family of compounds with potent antiparasitic activity, which they named avermectins. Avermectins are secondary metabolites, compounds not essential for the organism's growth but produced to provide an advantage, such as defense against competing organisms.

This groundbreaking discovery was the result of a collaboration with American parasitologist William Campbell and his team at Merck & Co. The partnership allowed for the in-depth screening and testing of these novel compounds. The extraordinary effectiveness of avermectin against a wide range of parasites in animals quickly became apparent. For this work, Ōmura and Campbell were jointly awarded the Nobel Prize in Physiology or Medicine in 2015, recognizing the immense impact of this discovery on global health.

The semisynthetic creation of ivermectin

While avermectin is a natural product, ivermectin is not. Instead, it is a semisynthetic derivative, meaning it is a compound that is chemically modified from a naturally occurring substance. The process to create ivermectin from its natural precursor, avermectin, involves a crucial step called selective hydrogenation.

The chemical modification process

Fermentation: The process starts with the large-scale fermentation of the Streptomyces avermitilis bacteria, which produces the avermectin compounds. The resulting mixture contains several types of avermectins, primarily avermectin B1a and B1b.
Hydrogenation: The avermectin B1 compounds have a double bond at the C22-C23 position. During the semisynthetic process, this double bond is selectively hydrogenated, or reduced, turning it into a single bond.
Purification and Formulation: The resulting compound, a mixture of 22,23-dihydroavermectin B1a and B1b, is what we know as ivermectin. It is then purified and formulated into the final oral tablets or topical applications used in medicine today.

This chemical modification enhances the drug's effectiveness and safety profile. The semisynthetic approach allows manufacturers to produce a more consistent and potent product than the original natural extract alone.

Natural vs. Semisynthetic vs. Synthetic

To fully understand why ivermectin is not considered a natural product, it is helpful to compare it to other types of drugs.


Feature	Natural Product	Semisynthetic Drug	Synthetic Drug
Origin	Isolated directly from a natural source, such as a plant, animal, or microorganism.	Starts with a natural compound, but undergoes chemical modification in a laboratory.	Created entirely from man-made chemical reactions in a laboratory.
Source Example	Penicillin (from Penicillium fungus)	Ivermectin (from avermectin, which is from Streptomyces avermitilis)	Aspirin (acetylsalicylic acid, synthesized from salicylic acid)
Modification	No chemical alteration from its natural form.	Significant chemical changes made to improve its properties.	None, as it is constructed from scratch.
Benefits	Often complex and evolutionarily optimized structures.	Improved potency, safety, and stability compared to the natural starting material.	Greater control over the final structure and properties.

The pharmacology of a semisynthetic success

Ivermectin's success is rooted in its highly selective mechanism of action. It binds specifically to glutamate-gated chloride ion channels found in the nerve and muscle cells of many parasites and insects. This binding causes an influx of chloride ions, leading to paralysis and eventual death of the parasite.

Selective Target: These channels are exclusive to invertebrates, meaning they are not found in humans, giving ivermectin a wide margin of safety.
Wide Applicability: Its broad-spectrum efficacy against both internal and external parasites made it a game-changer for treating diseases like onchocerciasis (river blindness) and lymphatic filariasis.
Public Health Impact: For decades, ivermectin has been a cornerstone of global public health campaigns, especially in low-income countries where parasitic diseases are prevalent.

Conclusion: The complexity of a 'wonder drug'

In conclusion, while the initial active compounds were discovered from a soil microbe, is ivermectin a natural product? No, it is not. The modern medication is a product of sophisticated medicinal chemistry that refined a natural substance into a more potent and effective drug. The distinction highlights the innovative process of drug development, where inspiration from nature is combined with synthetic chemical techniques to create life-saving pharmaceuticals. The story of ivermectin is a testament to the powerful combination of natural discovery and scientific ingenuity. For more detail on the antiparasitic activity and research surrounding this drug, the ScienceDirect article "Antiparasitic activity of ivermectin" offers comprehensive information.

Frequently Asked Questions

Ivermectin originates from avermectin, a natural compound produced during the fermentation of the bacterium Streptomyces avermitilis, a soil microbe originally isolated in Japan.

A natural product is isolated directly from a natural source without chemical modification, while a semisynthetic drug starts with a natural compound that is chemically altered in a lab to improve its efficacy or safety.

Avermectin is converted to ivermectin through a chemical reaction called selective hydrogenation, which modifies a specific double bond in the molecule.

The distinction is important for understanding the drug's development. The semisynthetic modification improves the drug's potency and reduces its toxicity compared to the raw natural extract.

Other examples of semisynthetic drugs include certain penicillin derivatives like amoxicillin and semisynthetic opioids like heroin, which are derived from morphine.

The primary purpose and proven effectiveness of ivermectin are against parasitic infections. Despite early lab studies, rigorous clinical research has found no significant benefit from its use to treat viral infections like COVID-19.

The discovery of avermectin, the precursor to ivermectin, was a collaborative effort involving Japanese microbiologist Satoshi Ōmura and American parasitologist William C. Campbell, who were awarded the Nobel Prize in 2015 for their work.