HIV-1 protease and reverse transcriptase inhibition by tiger milk mushroom (Lignosus rhinocerus) sclerotium extracts: In vitro and in silico studies

Abstract

Background and aim Lignosus rhinocerus (LR) is an edible mushroom with a variety of medicinal properties such as neurostimulation, immunomodulation, anti-inflammation, anti-oxidation, anti-proliferation, anti-diabetes and especially antiviral activity. Human immunodeficiency virus type-1 (HIV-1) needs the HIV-1 protease (PR) and reverse transcriptase (RT) for its replication. Therefore, both HIV-1 PR and RT are important targets for antiretroviral drug development. Experimental procedure The crude hexane (LRH), ethanol (LRE) and water (LRW) extracts of LR were in vitro screened for inhibitory activity against HIV-1 PR and RT, then anti-HIV-1 activity on the infected MOLT-4 cells were determined. Chemical constituents of the extracts were identified by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography (LC)-MS. The identified compounds were in silico analysed for drug-likeness property and molecular modelling. Results and conclusion According to our screening assays, LRE and LRW significantly inhibited both enzymes (25–55%), while LRH suppressed only the HIV-1 PR activity (88.97%). At 0.5 mg/ml of LRW showed significant inhibition of HIV-1 induced syncytial formation and p24 production in the infected MOLT-4 cells. Investigation of chemical analysis revealed that major groups of identified constituents found in the extracts were fatty acids, peptides and terpenoids. In silico analysis showed that heliantriol F and 6 alpha-fluoroprogesterone displayed great binding energies with HIV-1 PR and HIV-1 RT, respectively. These findings suggest that LR could be a potential source of compounds to inhibit HIV-1 PR and/or RT activities in vitro . Furthermore, our results provide beneficial data for the development of novel HIV-1 PR and RT inhibitors.

Natural Bioactive Compounds from Fungi as Potential Candidates for Protease Inhibitors and Immunomodulators to Apply for Coronaviruses

“…Twenty-five metabolites were isolated from the fruiting body of G. sinnense, and it was found that ganoderic acid GS-2, 20-hydroxylucidenic acid N, 20(21)-dehydrolucidenic acid N and ganoderiol F exhibited a high potential to inhibit HIV-1 protease activity [83]. Notably, crude extracts of tiger milk mushroom (Lignosus rhinocerus) displayed inhibitory activity against HIV-1 protease activity on infected cells, while in silico analysis showed that heliantriol F displayed significant binding energy at -12.57 kcal/mol on the active site of HIV-1 protease [84]. Hexane extract fractions obtained from a jelly fungus (Auricularia polytricha) could effectively inhibit HIV-1 protease activity in vitro, while four major compounds, ergosterol, linoleic acid and two triacylglycerols were found to be present [85].…”

Neuroprotective Effects of Extracts from Tiger Milk Mushroom Lignosus rhinocerus Against Glutamate-Induced Toxicity in HT22 Hippocampal Neuronal Cells and Neurodegenerative Diseases in Caenorhabditis elegans

“…The Tiger Milk Mushroom Lignosus rhinocerus (LR), found in Southeast Asia and China, has been used in folk medicine for asthma treatment [ 9 ]. Furthermore, this mushroom has anti-inflammatory, antioxidant, anti-proliferative, immuno-modulating and anti-HIV-1 activities in addition to a promotion of neurite outgrowth in PC-12 cells [ 10 , 11 , 12 ]. The bioactive compounds of LR consist of 1,3-β- and 1,6-β-glucans which are in a group of β-D-glucose polysaccharides, lectin which is a glycoprotein, laccase which is a copper-containing oxidase enzyme and other fungal immune-modulatory proteins (FIPs), and antioxidant proteins [ 13 ].…”

Bioactive compounds from fungi with antiviral activities: Mechanism of action and biosynthetic pathways

“…In particular, these bioactive molecules with antiviral effect have been classified as polyketides, indole alkaloids, terpenoids, nonribosomal peptides, polyketides, and hybrids of non-ribosomal peptides, fatty acids, ergosterol peroxide etc. These fungal bioactive compounds have been reported to be produced by Lignosus, Penicillium, Stachybotrys, Aspergillus, Cladosporium, Alternaria, Ganoderma, Fusarium, Phoma and Xylaria species among others (He et al, 2013;Peng et al 2013: Raekiansyah et al, 2017Zhao et al, 2017;Sillapachaiyaporn & Chuchawankul, 2020) (Table 1).…”