Scholars from Chiang Mai University and the Royal Thai Academy of Sciences published a retrospective paper in Molecules in April this year. Based on the research results published in the journals in the past, this paper lists the fungal active ingredients that have the potential to be further developed into coronavirus drug candidates with "inhibiting viral proteases" and "modulating immune response" as screening targets. As a result, polysaccharides, triterpenes and immunomodulatory proteins from Ganoderma lucidum were all among them.

Block viral proliferation by inhibiting viral protease activity

Because viruses must rely on cells to survive and proliferate, the so-called "antiviral drugs" have a mechanism of action that "interferes with the virus's replication process within the cell", preventing the virus from producing more virus through the cell.

Inhibition of viral protease (protease) is an important target that can interfere with viral replication. Just like the clinically successful AIDS drugs, the principle of action is almost related to the HIV-1 protease that inhibits HIV virus.

Because the replication process of HIV virus is similar to that of coronavirus, many HIV-1 protease inhibitors have also been proven to inactivate coronavirus proteases under in vitro experimental conditions. In addition, there are successful case where HIV-1 protease inhibitors have been used clinically to treat SARS, MERS And COVID-19 (New Coronary Pneumonia), so "inhibition of HIV-1 protease" has become one of the indicators for screening coronavirus drug candidates.

The team at Chiang Mai University then listed fungal ingredients that have been published in scientific journals and have HIV-1 protease inhibitory activity as potential drug candidates for treating coronavirus. A large part of these drug candidates were various triterpene compounds isolated from Ganoderma (Table 1).

Prevent immune response from being overdone or underdone through immune regulation

In addition to inhibiting viral proliferation, the team at Chiang Mai University also listed "immunoregulation" as a screening criterion for coronavirus drug candidates.

Because according to the existing clinical experience, whether a person is infected with SARS coronavirus (SARS-CoV) or new coronavirus (SARS-CoV-2), it is possible that the immune response of the infected person will be caught in the "overdone and underdone" dilemma – “Underdone” can't stop the virus; if “overdone”, the inflammatory reaction will damage the organ like wildfire.

Therefore, if the immune response can be adjusted back to the right balance as soon as possible, it is possible to prevent the invasion of the virus while reducing damage to organs, accelerating the speed of recovery and reducing the chance of death.

The team at Chiang Mai University put a list of active ingredients of mushrooms that have been scientifically proven to regulate immunity in the past as a reference for the development of new coronavirus drugs. Immunomodulatory proteins, polysaccharides and triterpenes from Ganoderma lucidum are also among the list (Table 2).

The resourceful world of fungi has always been a natural treasure trove of clinical drugs.

When the virus invades the body, the virus is immediately eliminated by the immune system, which is undoubtedly the best way to prevent virus infection. Inhibiting the proliferation of viruses, controlling the number and destructive power of the virus in the body and relying on the patient's own immune system to clear the virus and infected cells can be nothing more than an ideal way to treat viral infections.

From the analysis of Thai scholars, it can be seen that Ganoderma lucidum not only has abundant virus protease inhibitors but also has a variety of immunomodulators. Ganoderma lucidum seems to be a natural cocktail formulation for the prevention and treatment of coronavirus, and it is also a natural treasure trove of new drug resources.

In fact, since ancient times, the resourceful world of fungi has been a treasure trove of clinical drugs. For example, paclitaxel is widely used in cancer treatment. And the antibiotic penicillin is used to treat bacterial infections. Both of them which are originally derived from fungi.

Therefore, Thai scholars have sorted out fungal active ingredients through literature review, which is indeed very valuable for the development of coronavirus drugs or adjuvant therapy. Will the listed Ganoderma lucidum ingredients have the opportunity to be developed into drugs against coronavirus? Let’s wait and see.

【Reference】

Suwannarach N, et al. Natural Bioactive Compounds from Fungi as Potential Candidates for Protease Inhibitors and Immunomodulators to Apply for Coronaviruses. Molecules. 2020, 25(8): 1800. doi:10.3390/molecules25081800.

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