摘要
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^(®)(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^(®),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(IC_(50)=1.161±0.148 mg mL^(-1)).The low-molecular weight(LMW)fraction also demonstrated dose-dependent inhibition of ACE2 activity(IC_(50)=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-proteinRBD 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.
基金
funded by the Ministry of Higher Education Malaysia via the Fundamental Research Grant Scheme(FRGS/1/2022/STG02/UM/01/1)
the Bantuan Khas Penyelidikan-Kecemerlangan Penyelidikan 2023 Universiti Malaya,Malaysia[Grant no.:BKP007-2023-KP].
