Ophiocordyceps sinensis, formerly Cordyceps sinensis and colloquially known as caterpillar fungus, is an insect-pathogenic fungus in the family Ophiocordycipitaceae. It is primarily found in high-altitude regions of the Tibetan Plateau. It parasitizes larvae of ghost moths and produces a fruiting body which is valued in traditional Chinese medicine and Nepalese medicine as an aphrodisiac.Interview with Britt Bunyard on However, naturally harvested fruiting bodies often contain high amounts of arsenic and other heavy metals, making them potentially toxic. As a result, their sale has been strictly regulated by China's State Administration for Market Regulation since 2016.《总局关于停止冬虫夏草用于保健食品试点工作的通知 -食药监食监三〔2016〕21号》

O. sinensis parasitizes the larvae of moths within the family Hepialidae, specifically genera found on the Tibetan Plateau and in the Himalayas between elevations of . found across Tibet, the Himalayan regions of India, Bhutan and Nepal, and several Chinese provinces (Qinghai, Sichuan, and Yunnan). The fungus germinates in the living larva, kills and mummifies it, and a fruiting body emerges from the corpse as an upright stalk.

O. sinensis is classified as a medicinal mushroom, and its use has a long history in traditional Chinese medicine as well as in traditional Tibetan medicine. It is marketed for various health benefits but lacks sufficient scientific evidence for safety or effectiveness, and quality can vary due to inconsistent processing and labeling. The hand-collected, intact fungus-caterpillar body is valued by herbalists as medicine, and because of its cost, its use is also a status symbol.

The fruiting bodies of the fungus are not cultivated commercially outside of China,Hsieh, C., et al., A Systematic Review of the Mysterious Caterpillar Fungus Ophiocordyceps sinensis in Dong-ChongXiaCao and Related Bioactive Ingredients. Vol. 3. 2013. 16–32. but the mycelium form can be cultivated in vitro. Overharvesting and overexploitation have led to the classification of O. sinensis as an endangered species in China. Additional research needs to be carried out in order to understand its morphology and growth habits for conservation and optimum utilization.

Taxonomic history and systematics

Morphological features Ophiocordyceps sinensis consists of two parts, a fungal endosclerotium (within the caterpillar) and stroma. The stroma varies from dark brown or black, but can be a yellow color when fresh, and longer than the caterpillar itself, usually 4–10 cm. It grows singly from the larval head, and is clavate, sublanceolate or fusiform, and distinct from the stipe (stalk). The stipe is slender, glabrous, and longitudinally furrowed or ridged.

The fertile part of the stroma is the head. The head is granular because of the ostioles of the embedded perithecia. The perithecia are ordinally arranged and ovoid. The asci are cylindrical or slightly tapering at both ends, and may be straight or curved, with a capitate and hemispheroid apex, and may be two to four spored. Similarly, ascospores are hyaline, filiform, multiseptate at a length of 5–12 μm and subattenuated on both sides. Perithecial, ascus and ascospore characters in the fruiting bodies are the key identification characteristics of O. sinensis.

Ophiocordyceps species produce whole ascospores and do not separate into part spores. This is different from other Cordyceps species, which produce either immersed or superficial perithecia perpendicular to stromal surface, and the ascospores at maturity are disarticulated into part spores. Generally, Cordyceps species possess brightly colored and fleshy stromata, but O. sinensis has dark pigments and tough to pliant stromata, a typical characteristic feature of most of the Ophiocordyceps species.

Developments in classification

The species was first described scientifically by Miles Berkeley in 1843 as Sphaeria sinensis. The species was later reclassified Cordyceps in 1878 by Pier Andrea Saccardo. The fungus was known as Cordyceps sinensis until 2007, when molecular analytical techniques were used to amend the classification of Cordycipitaceae and Clavicipitaceae, resulting in the naming of a new family Ophiocordycipitaceae and the reclassification of several Cordyceps species, including C. sinensis, to the genus Ophiocordyceps.

Common names In Tibet, it is known as yartsa gunbu, (, "summer grass winter worm"). The name was first recorded in the 15th century by the Tibetan doctor Zurkhar Namnyi Dorje. In colloquial Tibetan, yartsa gunbu is often shortened to "yartsa" or "bu". The Tibetan name is transliterated in Nepali as यार्चागुन्बू, यार्चागुन्बा, yarshagumba, yarchagumba or yarsagumba. The transliteration in Bhutan is .

In India, it is known as keera jhar, keeda jadi, keeda ghas or in Nepali, Hindi and Garhwali.

It is known in Chinese as (冬蟲夏草), meaning "winter worm, summer grass", which is a literal translation of the original Tibetan name. In traditional Chinese medicine, its name is often abbreviated as chong cao (蟲草 "insect plant"), a name that also applies to other Cordyceps species, such as C. militaris. In Japanese, it is homophonically read as , while in Korean and Vietnamese it is known by the transliterated forms of the Chinese word, dongchunghacho (동충하초) and đông trùng hạ thảo respectively. Some Chinese English-language texts refer to Cordyceps sinensis as āweto, which is the Māori name for Ophiocordyceps robertsii, a species from south-eastern Australia and New Zealand.Hill H. Art. XXXVI: The Vegetable Caterpillar (Cordiceps robertsii). Transactions and Proceedings of the Royal Society of New Zealand. Vol 34, 1901;396–401

The English term "vegetable caterpillar" is a misnomer, as no plant is involved. "Caterpillar fungus" is a preferred term.

Synonyms Since the 1980s, 22 species in 13 genera have been attributed to the anamorph (asexually reproducing mold-like form) of O. sinensis.

+Anamorphs attributed to O. sinensis Anamorph Correct Teleomorph Method for identification/Reference Cephalosporium acreomonium Umbelopsis Chrysosporium sinense ? (not O. sinensis) RAPD polymorphism similarity Cephalosporium dongchongxiacae (invalid name) O. sinensis Cephalosporium sp. sensu (incomplete name) | O. sinensis

| Hirsutella sinensis (invalid name but commonly used) O. sinensis; ITS sequence; microcyclic conidiation from ascospores and molecular studies Hirsutella hepiali O. sinensis Cephalosporium sinensis Possibly O. sinensis there is lack of valid information Isaria farinosa Paecilomyces farinosus Isolates reported as Isaria sp., Verticella sp., Scydalium sp. Unknown, identification is dubious Mortierella hepiali Unknown Zygomycota Paecilomyces sinensis ? (not O. sinensis) molecular evidence Sporothrix insectorum ? (not O. sinensis) molecular evidence Paecilomyces lingi ? incomplete information, only appeared in one article Tolypocladium sinense ? no valid information as of 2002 Paecilomyces hepiali ? Confirmed to be its own species, now Samsoniella hepiali Tolypocladium sinense ? no valid information as of 2002Jiang, Y. Y., & Yao, Y. J. (2002). Names related to Cordyceps sinensis anamorph. Mycotaxon, 84:245-254.

Additional synonyms for the teleomorph are Cordyceps nepalensis and C. multiaxialis. They have similar morphological characteristics to O. sinensis, also had almost identical or identical ITS sequences and its presumed anamorph, H. sinensis.

Ecology and life cycle

Caterpillars prone to infection by O. sinensis generally live underground in alpine grass and shrub-lands on the Tibetan Plateau and the Himalayas at an altitude between . The fungus is reported from the northern range of Nepal, Bhutan, and also from the northern states of India, apart from northern Yunnan, eastern Qinghai, eastern Tibet, western Sichuan, southwestern Gansu provinces. Fifty-seven taxa from several genera (37 Thitarodes, 1 Bipectilus, 1 Endoclita, 1 Gazoryctra, 3 Pharmacis, and 14 others not correctly identified to genus) are recognized as potential hosts of O. sinensis.

The stalk-like dark brown to black fruiting body (or mushroom) grows out of the head of the dead caterpillar and emerges from the soil in alpine meadows by early spring. During late summer, the fruiting body disperses spores. The caterpillars, which live underground feeding on roots, are most vulnerable to the fungus after shedding their skin, during late summer. In late autumn, chemicals on the skin of the caterpillar interact with the fungal spores and release the fungal mycelia, which then infects the caterpillar.

The infected larvae tend to remain underground vertical to the soil surface with their heads up. After invading a host larva, the fungus ramifies throughout the host and eventually kills it. Gradually the host larvae become rigid because of the production of fungal sclerotia. Fungal sclerotia are multihyphal structures that can remain dormant and then germinate to produce spores. After overwintering, the fungus ruptures the host body, forming the fruiting body, a sexual sporulating structure (a perithecial stroma) from the larval head that is connected to the sclerotia in the dead larva below ground and grows upward to emerge from the soil to complete the cycle.

The slow growing O. sinensis grows at a comparatively low temperature, i.e., below 21 °C. Temperature requirements and growth rates are crucial factors that distinguish O. sinensis from other similar fungi. Climate change is suspected to be negatively affecting the mountain organism.

Use in traditional Asian medicines

The use of caterpillar fungus as folk medicine apparently originated in Tibet and Nepal. So far the oldest known text documenting its use was written in the late 15th century by the Tibetan doctor Zurkhar Nyamnyi Dorje (Wylie: ) [1439–1475]) in his text: ("Instructions on a Myriad of Medicines"), where he describes its use as an aphrodisiac.

The first mention of Ophiocordyceps sinensis in traditional Chinese medicine was in Wang Ang's 1694 compendium of materia medica, Ben Cao Bei Yao. In the 18th century it was listed in Wu Yiluo's Ben cao cong xin ("New compilation of materia medica"). The ethno-mycological knowledge on caterpillar fungus among the Nepalese people is documented.nepjol.info, Devkota(2006) The entire fungus-caterpillar combination is hand-collected for medicinal use.

In traditional Chinese medicine, it is regarded as having an excellent balance of yin and yang as it is considered to be composed of both an animal and a vegetable.

Wild-collected "cordyceps" is not always true O. sinensis, even when the location and the host insect matches. This has resulted in the description of new species such as Cordyceps liangshanensis (Liangshan, China; many Nepali "cordyceps" are also incorrectly identified to be this species, and no new names for them have been proposed yet) and Samsoniella hepiali (Qinghai, China). Despite not being the same species when examined using a modern method, these species are used in broadly the same way in traditional medicine. There are also "cordyceps" species that are traditionally known to be different from O. sinensis but nevertheless thought to be have a similar tonifying action. China is home to at least 299 species of "cordyceps" in this broadest sense.

It is marketed for various health benefits but lacks sufficient scientific evidence for safety or effectiveness, and quality can vary due to inconsistent processing and labeling.

Secondary metabolites

A 2008 source reports that O. sinensis contains cordycepin, an adenosine derivative originally discovered in C. militaris. However, this study uses store-bought material labeled as O. sinensis without any molecular confirmation that it is indeed the species. A more in-depth 2017 study, which fully characterized the biosynthetic machinery for cordycepin, found that O. sinensis does not produce cordycepin. This discrepancy underscores the importance of correctly identifying "cordyceps" species.

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