Goh, Neng-Yao and Yap, Yeannie Hui-Yeng and Ng, Chyan Leong and Kong, Boon Hong and Ng, Szu-Ting and Tan, Chon-Seng and Razif, Muhammad Fazril Mohamad and Fung, Shin Yee (2024) Water-soluble compounds from Lignosus rhinocerus TM02 ® (xLr™) modulate ACE2 activity and inhibit its interaction with SARS-CoV-2 spike-protein. Food Bioscience, 59. p. 104232. ISSN 2212-4292, DOI https://doi.org/10.1016/j.fbio.2024.104232.
Full text not available from this repository.Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a coronavirus that causes COVID-19 by attaching its spike protein (S-protein) to the ACE2 receptor on host cells. This interaction is critical for viral entry and infection. Water-soluble compounds found in the medicinal mushroom Lignosus rhinocerus TM02 (R) (Tiger Milk mushroom) may potentially reduce the risk of SARS-CoV-2 infection by modulating human ACE2 activity, shielding it from binding with the S-protein. In this study, the cold-water-extract (xLr (TM)) and bioactive fractions of TM02 (R), a standardized L. rhinocerus cultivar, were evaluated for their potentials to modulate ACE2 activity and prevent SARS-CoV-2 spike protein-ACE2 binding. Both xLr (TM) and its high-molecular weight (HMW) fraction exhibited low ACE2 inhibitory activities (<20% inhibition), while the medium-molecular weight (MMW) fraction demonstrated both dose- and time-dependent inhibitions (IC50 = 1.161 +/- 0.148 mg mL(-1)). The low-molecular weight (LMW) fraction also demonstrated dose-dependent inhibition of ACE2 activity (IC50 = 1.818 +/- 0.233 mg mL(-1)), without affecting SARS-CoV-2 spike protein binding to the former. Molecular docking simulations revealed that xLr (TM) LMW molecules are able to bind to the ACE2 substrate enzymatic site, rather than the S-protein(RBD) binding site. xLr (TM), and its HMW and MMW fractions successfully suppressed SARS-CoV-2 spike protein-ACE2 binding in a dose-dependent manner (>95% inhibition at 10 mg mL(-1)). The observed inhibitory activities are likely attributed to its protein and/or polysaccharide-protein complexes, such as fungal immunomodulatory proteins (FIPs) or serine proteases. Overall, the water-soluble protein and polysaccharide-protein complexes found in the HMW and MMW of xLr (TM) have promising potential to reduce SARS-CoV-2 viral pathogenesis through its modulatory action on human ACE2.
| Item Type: | Article |
|---|---|
| Funders: | Ministry of Higher Education Malaysia via the Fundamental Research Grant Scheme (FRGS/1/2022/STG02/UM/01/1), Bantuan Khas Penyelidikan - Kecemerlangan Penyelidikan 2023 Universiti Malaya, Malaysia (BKP007- 2023-KP) |
| Uncontrolled Keywords: | SARS-CoV-2 virus; Spike protein receptor-binding domain; COVID-19; Angiotensin-converting enzyme 2; TM02 (R) cold-water-extract; xLr (TM); Polysaccharide-protein complexes |
| Subjects: | R Medicine |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 20 Sep 2024 05:09 |
| Last Modified: | 20 Sep 2024 05:09 |
| URI: | http://eprints.um.edu.my/id/eprint/45173 |
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