Molecules that display promising effects against COVID-19 are appearing in unlikely places — including the fruiting bodies of bug-eating fungi. Regarded as a fungal therapeutic biofactory, the medicinal mushroom cordyceps contains a plethora of active metabolites. Among these, cordycepin stands out as a potential treatment for a host of chronic diseases. The compound exhibits antioxidant, anti-tumour, anti-inflammatory, anti-viral, neuroprotective, and even pro-sexual actions.
Now, researchers are exploring the effects of cordycepin against COVID-19. The lack of specific treatments for the virus has driven teams of scientists from around the world to focus their attention on alternative therapies. So far, they’ve explored the efficacy of vitamin C and D, echinacea, and melatonin in reducing the severity of the disease and the pathogen that causes it — SARS-CoV-2.
A paper published within the Journal of Biomolecular Structure and Dynamics documents the use of a computer simulation in examining the ability of cordycepin to disrupt the infection and replication of SARS-CoV-2. The researcher — Akalesh Verma — selected cordycepin as a candidate based on previous studies that demonstrate the antiviral activities of the metabolite against influenza, rotavirus, and Epstein-Barr virus.
Using computational medicine — a technique currently used to test pharmaceutical drugs against the virus — Verma downloaded 3-dimensional crystal structures of cordycepin and components responsible for the replication, survival, and multiplication of SARS-CoV-2.
The virus consists of a single strand of RNA housed within a spherical envelope. Spike proteins protrude from this outer layer, giving the pathogen its crown-like appearance. These structures underpin the infection process. They enable the virus to bind to ACE2 receptors in the lungs and fuse to human cells.
Once attached, the envelope releases the RNA strand into the host, where the code hijacks the cell’s protein manufacturing apparatus to create copies of itself — fuelling replication. The virus features a component called a main protease which enables it to utilize the proteins within the cell.
Scientists consider the spike proteins and main protease attractive targets for drugs. Inhibiting the spike protein would minimize the ability of SARS-CoV-2 to bind to receptors in the lungs. While going after the main protease would interrupt the virus’ ability to multiply.
Verma obtained computer models of these vital components and tested virtual cordycepin against them using a molecular interaction simulation. The study revealed the strong ability of cordycepin to bind to the spike protein. Other pharmaceuticals that achieve this outcome could successfully restrict the virus from entering host cells. Computer analysis also revealed cordycepin’s potent affinity for the main protease binding site.
Upon analysing the results of this research, Verma concluded, “Since cordycepin has both pre-clinical and clinical information about antiviral activities, therefore; it is suggested to the world community to undertake repurposing cordycepin to test efficacy and safety for the treatment of COVID-19”.
Interestingly, cordycepin shares a similar molecular structure to adenosine. Present in every cell in the human body, this metabolite assists in signalling pathways and energy transfer. Adenosine works to combat viruses by destabilizing messenger RNA and disrupting the creation of proteins, leading researchers to suggest that elevated levels might serve a therapeutic function in the face of SARS-CoV-2. Because enzymes in the body cannot distinguish between adenosine and cordycepin, the latter also takes part in these defensive biochemical reactions.
As well as potentially inhibiting the virus itself, cordycepin may help to alleviate some of the damage it causes in the form of the disease COVID-19. In severe cases, the virus catalyses amplified symptoms of acute respiratory distress syndrome (ARDS). This phenomenon stems from an overly aggressive inflammatory immune response that results in a cytokine storm. Characterised by fluid build up in the lungs and shortness of breath, ARDS reduces the ability of patients to breathe.
Cordycepin demonstrates anti-inflammatory effects in cases of inflammatory lung diseases such as asthma and acute lung injury. It achieves this outcome by delaying and suppressing the release of inflammatory cytokines from immune cells. After reviewing the data surrounding this mechanism of action, researchers from the Cheng Du University in China stated, “Moreover, cordycepin enhanced immunity, inhibited the proliferation of viral RNA, and suppressed cytokine storms, thereby suggesting its potential to treat COVID-19 and other viral infections”.
COVID-19 can also lay the groundwork for a condition known as superinfection. While preoccupied with the original pathogen, the body remains vulnerable to additional infection at the hands of other viruses and bacteria. Research published in the European Journal of Pharmacology offers insight into the anti-inflammatory and antioxidant effects of cordycepin against the acute lung injury that arises from infections such as bacterial pneumonia. On top of this, cordycepin directly kills bacterial cells by inflicting damage upon their membranes.
As an entomopathogenic fungus, cordyceps requires an insect host to produce a fruiting body in the wild. Known widely as the “zombie mushroom”, cordyceps spores inoculate living insects and release hyphal threads known collectively as mycelium. This living matrix uses the insect host as a substrate, forms a spore-bearing mushroom, and begins the reproductive cycle once more.
Consisting of over 700 species, two members of the cordyceps genus are prized within traditional Chinese medicine. Utilized for centuries, both cordyceps sinensis and cordyceps militaris contain cordycepin. Although chemically similar, the two species feature a distinct difference: rarity.
Cordyceps militaris grows throughout the Northern Hemisphere, and cultivators across the world grow the fungus on a large scale. In contrast, cordyceps sinensis only grows on the Tibetan plateau, and mushroom farmers have yet to crack the code of cultivation. For this reason, high-quality specimens fetch a price of up to $140,000 per kilo — triple the price of gold.
This staggering value has led to the overharvesting of this rare lifeform. In the interest of environmental sustainability, conscious consumers are opting for cultivated cordyceps militaris as a source of cordycepin. Additionally, cordyceps militaris appears to produce higher levels of cordycepin compared to its premium counterpart.
Luke Sumpter is a freelance journalist that specializes in health, wellness, and alternative therapies. Currently, he’s working on a dissertation exploring the emerging role of the endocannabinoid system in orthopaedic medicine.