Certain steroid compounds of the medicinal mushrooms endemic to Taiwan (known as antcins) can inhibit a host cell receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and thus prevent viral infection. and subsequent development of coronavirus disease (COVID-19), reports new study published in MDPI journal Plants.
Despite the global distribution of vaccines aimed at stopping the ongoing COVID-19 pandemic, cases and deaths are still on the rise due to the unavailability of effective drugs that would help prevent or slow SARS infection- CoV-2. So a double punch of a vaccine and a drug is probably what we need to solve this pandemic.
Thus, the search for the best drug candidate continues. One of the primary targets of anti-COVID-19 compounds is the angiotensin-converting enzyme 2 (ACE2), which is actually a host cell surface receptor exploited by SARS-CoV-2 to initiate the entire infectious process.
We already know the important role of medicinal herbs in the prevention and treatment of certain diseases, while several phytocompounds have been shown to have ACE2 inhibitory activity. Therefore, they are studied in depth using different computer, preclinical and clinical models.
Antrodia cinnamomea and Antrodia salmonea are two endemic fungi found in Taiwan with many pharmacological activities. As a result, their potential use against SARS-CoV-2 was recently explored by a group of authors from National Chung Hsing University in Taiwan.
Moving from in silico cell line studies
Briefly, these authors explored the inhibitory effects of various anticins against ACE2 receptors. Anticins are steroid-like compounds produced by the aforementioned endemic fungi, and this study aimed to evaluate the properties of antcin-A, antcin-B, antcin-C, antcin-H, antcin 99% pure -I and antcin-M.
Chemical structure of anticines.
For this purpose, they used a human colorectal adenocarcinoma (HT-29) cell line, while the cellular activity of ACE2 was measured using a human ACE2 enzyme immunoassay (ELISA) available in trade. The cytotoxicity of various anticins on HT-29 cells was also determined before studying the inhibitory effects.
Based on the results of a specific colorimetric assay, the researchers selected optimal non-cytotoxic concentrations of antcins to use in their experiments. Due to its cytotoxicity, antcin-K was in fact removed from their list for further investigation.
Effectively reduce ACE2 levels
The researchers found that all of the treated anticins – except antcin-M – show significant inhibition of ACE2 activity. Specifically, there was a strong reduction in human ACE2 levels in HT-29 cells when antcin-A, antcin-B, antcin-C and antcin-I were used, and a moderate reduction was observed in antcin-H treated cells.
In addition, all of the anticins tested failed to inhibit the expression of the messenger RNA (mRNA) of ACE2 or TMPRSS2 (the latter being an endothelial cell surface protein involved in viral entry and spread of coronaviruses) in HT-29 cells, implying that the antcin -induced reduction of ACE2 was not the result of downregulation at the mRNA level.
This type of reduction in the expression of ACE2 and TMPRSS2 proteins in host cells may indeed represent a viable strategy for the prophylaxis and treatment of SARS-CoV-2 infection, as it can successfully arrest the disease. one of the most crucial events in human-to-human disease. transmission.
Still a long way from the hypothesis to the bedside
Recently, many natural products have been evaluated as potential solutions for the prevention or treatment of COVID-19, but most of these studies have used in silico models, i.e. computer modeling and simulations. This study went further and used reliable cell models.
“The hypothesis that the antcin-induced reduction of ACE2 was most likely related to the stability or degradation of the ACE2 protein via the proteasome pathway rather than to inhibition of transcription is reasonable.” , state the study authors in this article published in the journal Plants.
“We believe that further pharmacological, toxicological and bioavailability studies may support our hypothesis that anticins may be a potential ACE2 inhibitor for COVID-19 prophylaxis,” they add.
All of these conclusions should be considered strictly preliminary; thus, at the present time, it cannot be said that anticins will ever be valuable prophylactic or therapeutic agents for clinical use. However, the results look promising and these steroid-like compounds may well be an important addition in our fight against COVID-19.