First Discovery of Beta-Sitosterol as a Novel Antiviral Agent against White Spot Syndrome Virus

Chen, Cheng; Shen, Jing-Lei; Liang, Chang-Shuai; Sun, Zhong-Chen; Jiang, Haifeng

doi:10.3390/ijms231810448

Cited by 16 publications

(10 citation statements)

References 56 publications

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“…β-sitosterol (50 mg/kg), the main component of Pinellia ternata (Thunb.) Breit., was reported to inhibit ~95.79% of white spot syndrome virus (WSSV) in crayfish [ 113 ]. In addition, the stem bark, root, and leaf extracts of Erythrostemon yucatanensis (Greenm.)…”

Section: Resultsmentioning

confidence: 99%

Cheminformatics-Based Study Identifies Potential Ebola VP40 Inhibitors

Broni

Ashley

Adams

et al. 2023

IJMS

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The Ebola virus (EBOV) is still highly infectious and causes severe hemorrhagic fevers in primates. However, there are no regulatorily approved drugs against the Ebola virus disease (EVD). The highly virulent and lethal nature of EVD highlights the need to develop therapeutic agents. Viral protein 40 kDa (VP40), the most abundantly expressed protein during infection, coordinates the assembly, budding, and release of viral particles into the host cell. It also regulates viral transcription and RNA replication. This study sought to identify small molecules that could potentially inhibit the VP40 protein by targeting the N-terminal domain using an in silico approach. The statistical quality of AutoDock Vina’s capacity to discriminate between inhibitors and decoys was determined, and an area under the curve of the receiver operating characteristic (AUC-ROC) curve of 0.791 was obtained. A total of 29,519 natural-product-derived compounds from Chinese and African sources as well as 2738 approved drugs were successfully screened against VP40. Using a threshold of −8 kcal/mol, a total of 7, 11, 163, and 30 compounds from the AfroDb, Northern African Natural Products Database (NANPDB), traditional Chinese medicine (TCM), and approved drugs libraries, respectively, were obtained after molecular docking. A biological activity prediction of the lead compounds suggested their potential antiviral properties. In addition, random-forest- and support-vector-machine-based algorithms predicted the compounds to be anti-Ebola with IC50 values in the micromolar range (less than 25 μM). A total of 42 natural-product-derived compounds were identified as potential EBOV inhibitors with desirable ADMET profiles, comprising 1, 2, and 39 compounds from NANPDB (2-hydroxyseneganolide), AfroDb (ZINC000034518176 and ZINC000095485942), and TCM, respectively. A total of 23 approved drugs, including doramectin, glecaprevir, velpatasvir, ledipasvir, avermectin B1, nafarelin acetate, danoprevir, eltrombopag, lanatoside C, and glycyrrhizin, among others, were also predicted to have potential anti-EBOV activity and can be further explored so that they may be repurposed for EVD treatment. Molecular dynamics simulations coupled with molecular mechanics Poisson–Boltzmann surface area calculations corroborated the stability and good binding affinities of the complexes (−46.97 to −118.9 kJ/mol). The potential lead compounds may have the potential to be developed as anti-EBOV drugs after experimental testing.

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Section: Resultsmentioning

confidence: 99%

Cheminformatics-Based Study Identifies Potential Ebola VP40 Inhibitors

Broni

Ashley

Adams

et al. 2023

IJMS

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“…A recent in silico study suggested that β -sitosterol could suppress viral infection with SARS-CoV-2 through targeting the receptor-binding domain (RBD) of the spike glycoprotein [ 54 ]. Previous investigations have shown also that β -sitosterol exhibits antioxidant, anti-inflammatory, anticancer, and in vitro antiviral activity against white spot syndrome virus [ 51 , 52 , 53 , 54 ]. However, antiviral activities against IAVs, to the best of our knowledge, have not yet been reported.…”

Section: Discussionmentioning

confidence: 99%

Phytoestrogen β-Sitosterol Exhibits Potent In Vitro Antiviral Activity against Influenza A Viruses

et al. 2023

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Influenza is a contagious infection in humans that is caused frequently by low pathogenic seasonal influenza viruses and occasionally by pathogenic avian influenza viruses (AIV) of H5, H7, and H9 subtypes. Recently, the clinical sector in poultry and humans has been confronted with many challenges, including the limited number of antiviral drugs and the rapid evolution of drug-resistant variants. Herein, the anti-influenza activities of various plant-derived phytochemicals were investigated against highly pathogenic avian influenza A/H5N1 virus (HPAIV H5N1) and seasonal low pathogenic human influenza A/H1N1 virus (LPHIV H1N1). Out of the 22 tested phytochemicals, the steroid compounds β-sitosterol and β-sitosterol-O-glucoside have very potent activity against the predefined influenza A viruses (IAV). Both steroids could induce such activity by affecting multiple stages during IAV replication cycles, including viral adsorption and replication with a major and significant impact on the virus directly in a cell-free status “viricidal effect”. On a molecular level, several molecular docking studies suggested that β-sitosterol and β-sitosterol-O-glucoside exhibited viricidal effects through blocking active binding sites of the hemagglutinin surface protein, as well as showing inhibitory effects against replication through the binding with influenza neuraminidase activity and blocking the active sites of the M2 proton channel activity. The phytoestrogen β-sitosterol has structural similarity with the active form of the female sex hormone estradiol, and this similarity is likely one of the molecular determinants that enables the phytoestrogen β-sitosterol and its derivative to control IAV infection in vitro. This promising anti-influenza activity of β-sitosterol and its O-glycoside derivative, according to both in vitro and cheminformatics studies, recommend both phytochemicals for further studies going through preclinical and clinical phases as efficient anti-influenza drug candidates.

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“…One major compound, β -sitosterol, present in the LFOB, could block the immune responses mediated by RIG-I signaling and deleterious IFN production that could help to reduce the viral load [ 31 ]. Furthermore, it has also been reported that it interferes with viral gene expression and inhibits viral replication by interfering with viral immune signaling, hijacking pathways [ 32 ]. As of now, there are no reports available on β -sitosterol, stigmasterol and campesterol targeting DENV proteins.…”

Section: Discussionmentioning

confidence: 99%

“…The oven temperature programmed with linear mode went from 60 °C to 280 °C at a 3 °C/min ramp; using nitrogen (1.0 mL/min flow rate), for the injector and detector, temperatures were fixed at 290 °C and 300 °C, respectively. The injection volume was 1.0 μL of 1% solution, and the split ratio was set at 1:50 [ 30 , 31 , 32 ]. The ITQ 1100 interfaced Trace Ultra Gas Chromatography-Mass Spectroscopy (GC-MS) (Thermo Scientific, Waltham, MA, USA) was employed for qualitative analysis with the column mentioned above and GC oven temperature program using helium as a carrier gas at 1.0 mL/min.…”

Section: Methodsmentioning

confidence: 99%

Anti-Dengue Activity of Lipophilic Fraction of Ocimum basilicum L. Stem

Joshi¹,

Agrawal²,

Patil

et al. 2023

Molecules

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Ocimum basilicum L. is used to cure many types of fever in traditional medicine. This study aims to explore the antiviral activity of the lipophilic fraction of the stem of O. basilicum (LFOB) against dengue virus (DENV) and chikungunya virus (CHIKV). The LFOB was analyzed using GC-FID and GC-MS. The antiviral activity of LFOB was studied using the Vero CCL-81 cell line. The cytotoxicity assay was performed using 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). In vitro antiviral activity and FFU assay were used to determine and confirm antiviral activity against DENV and CHIKV. Twenty-six compounds were identified in LFOB using GC/MS. The most abundant compounds were β-sitosterol (22.9%), stigmasterol (18.7%), and campesterol (12.9%). Significant reduction in DENV titre was observed under pre- and post-infection treatment conditions at a concentration of 3.125 µg/mL, but no anti-CHIKV activity was observed. Our earlier and the present AutoDock-Vina-based in silico docking study revealed that β-sitosterol and stigmasterol could form strong interactions with the DENV E glycoprotein and DENV RdRp domain, respectively. Our findings suggest that LFOB can inhibit DENV infection and might act as a potent prophylactic/therapeutic agent against DENV-2. In silico results suggested that β-sitosterol and stigmasterol may block the viral entry by inhibiting the fusion process and viral replication respectively.

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First Discovery of Beta-Sitosterol as a Novel Antiviral Agent against White Spot Syndrome Virus

Cited by 16 publications

References 56 publications

Cheminformatics-Based Study Identifies Potential Ebola VP40 Inhibitors

Cheminformatics-Based Study Identifies Potential Ebola VP40 Inhibitors

Phytoestrogen β-Sitosterol Exhibits Potent In Vitro Antiviral Activity against Influenza A Viruses

Anti-Dengue Activity of Lipophilic Fraction of Ocimum basilicum L. Stem

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