Phyllanthin and hypophyllanthin, the isolated compounds of <i>Phyllanthus niruri</i> inhibit protein receptor of corona virus (COVID-19) through <i>in silico</i> approach

Marhaeny, Honey Dzikri; Widyawaruyanti, Aty; Widiandani, Tri; Hafid, Achmad Fuad; Wahyuni, Tutik Sri

doi:10.1515/jbcpp-2020-0473

Cited by 15 publications

(8 citation statements)

References 31 publications

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“…Several studies using bioinformatics to study drugs and biopharmaceutical products have been applied to explore a way to reduce the risk of COVID-19 effects in severe acute respiratory syndrome poor outcomes. 27,28 There are nine copies of CLEC5A within the asymmetric unit, representing a range of structural NAG binding on asparagine (Asn-343) is a binding site of the spike RBD structure and is unlikely to be part of the connection with hACE2. Pokhrel et al 46 mentioned that the only asparagine conserved in several variants and mutations found in spike RBD structure N-glycosylation sites is Asn-343.…”

Section: Discussionmentioning

confidence: 99%

“…Molecular docking provides important in silico information to preclinical studies based on protein–protein binding interactions. Several studies using bioinformatics to study drugs and biopharmaceutical products have been applied to explore a way to reduce the risk of COVID‐19 effects in severe acute respiratory syndrome poor outcomes 27,28 . There are nine copies of CLEC5A within the asymmetric unit, representing a range of structural conformers and so providing insight into the range of possibilities in the interactions that this receptor may adopt with different ligands in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…The C‐lectin receptors on myeloid cells are extremely important for innate immunity response concerning dysregulation induced by several viruses, as described previously, 27,28 but the absence of information about the interactions with SARS‐CoV‐2 proteins led us to investigate their participation in COVID‐19. Molecular docking experiments were performed to generate a complex between the CLEC5A receptor (PBD ID: 2YHF) and spike protein with the human angiotensin‐converting enzyme 2 (hACE2) receptor (PBD ID: 6LZG).…”

Section: Methodsmentioning

confidence: 99%

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CLEC5A expression can be triggered by spike glycoprotein and may be a potential target for COVID‐19 therapy

Machado

Santos

Azamor

et al. 2022

Journal of Medical Virology

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The immune response is crucial for coronavirus disease 19 (COVID‐19) progression, with the participation of proinflammatory cells and cytokines, inducing lung injury and loss of respiratory function. CLEC5A expression on monocytes can be triggered by viral and bacterial infections, leading to poor outcomes. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is able to induce neutrophil activation by CLEC5A and Toll‐like receptor 2, leading to an aggressive inflammatory cascade, but little is known about the molecular interactions between CLEC5A and SARS‐CoV‐2 proteins. Here, we aimed to explore how CLEC5A expression could be affected by SARS‐CoV‐2 infection using immunological tools with in vitro, in vivo, and in silico assays. The findings revealed that high levels of CLEC5A expression were found in monocytes from severe COVID‐19 patients in comparison with mild COVID‐19 and unexposed subjects, but not in vaccinated subjects who developed mild COVID‐19. In hamsters, we detected CLEC5A gene expression during 3–15 days of Omicron strain viral challenge. Our results also showed that CLEC5A can interact with SARS‐CoV‐2, promoting inflammatory cytokine production, probably through an interaction with the receptor‐binding domain in the N‐acetylglucosamine binding site (NAG‐601). The high expression of CLEC5A and high levels of proinflammatory cytokine production were reduced in vitro by a human CLEC5A monoclonal antibody. Finally, CLEC5A was triggered by spike glycoprotein, suggesting its involvement in COVID‐19 progression; therapy with a monoclonal antibody could be a good strategy for COVID‐19 treatment, but vaccines are still the best option to avoid hospitalization/deaths.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

CLEC5A expression can be triggered by spike glycoprotein and may be a potential target for COVID‐19 therapy

Machado

Santos

Azamor

et al. 2022

Journal of Medical Virology

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“…Genus Phyllanthus is one of the largest genus in the family Phyllanthaceae having 11 sub-genera compromising over 700 well-known species and are globally disseminated in the tropics and subtropics 13 . Phyllanthus niruri L. (Syn P. amarus Schum & Thonn) is a traditional pharmaceutical plant that has been described for its various medicinal activities such as hepatoprotective, antibacterial, antiviral, anti-diabetes, anti-obesity, antihyperlipidemic, and anti-inflammatory 14 – 17 .…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic and chemomodulatory effects of Phyllanthus niruri in MCF-7 and MCF-7ADR breast cancer cells

Abdel-Sattar

Allam

Al‐Abd

et al. 2023

Sci Rep

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The members of the genus Phyllanthus have long been used in the treatment of a broad spectrum of diseases. They exhibited antiproliferative activity against various human cancer cell lines. Breast cancer is the most diagnosed cancer and a leading cause of cancer death among women. Doxorubicin (DOX) is an anticancer agent used to treat breast cancer despite its significant cardiotoxicity along with resistance development. Therefore, this study was designed to assess the potential cytotoxicity of P. niruri extracts (and fractions) alone and in combination with DOX against naïve (MCF-7) and doxorubicin-resistant breast cancer cell lines (MCF-7ADR). The methylene chloride fraction (CH2Cl2) showed the most cytotoxic activity among all tested fractions. Interestingly, the CH2Cl2-fraction was more cytotoxic against MCF-7ADR than MCF-7 at 100 µg/mL. At sub-cytotoxic concentrations, this fraction enhanced the cytotoxic effect of DOX against the both cell lines under investigation (IC50 values of 0.054 µg/mL and 0.14 µg/mL vs. 0.2 µg/mL for DOX alone against MCF-7) and (1.2 µg/mL and 0.23 µg/mL vs. 9.9 µg/mL for DOX alone against MCF-7ADR), respectively. Further, TLC fractionation showed that B2 subfraction in equitoxic combination with DOX exerted a powerful synergism (IC50 values of 0.03 µg/mL vs. 9.9 µg/mL for DOX alone) within MCF-7ADR. Untargeted metabolite profiling of the crude methanolic extract (MeOH) and CH2Cl2 fraction exhibiting potential cytotoxicity was conducted using liquid chromatography diode array detector-quadrupole time-of-flight mass spectrometry (LC-DAD-QTOF). Further studies are needed to separate the active compounds from the CH2Cl2 fraction and elucidate their mechanism(s) of action.

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“…Phyllanthus niruri has been widely known in traditional medicine due to its various pharmacological activities, including anti-inflammation and anti-allergic (Marhaeny et al, 2021). Recently, P. niruri was shown to have antiasthmatic properties due to its role in reducing the number of mast cell degranulation (Mukherjee & Gupta, 2018).…”

Section: Introductionmentioning

confidence: 99%

Investigating the anti-allergic activity of Phyllanthus niruri via MALT1 protease inhibition: An in silico approach

Marhaeny,

Aliyah,

Miatmoko

et al. 2023

Pharm Educ

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Background: Allergic inflammation is a condition caused by complex interactions between several inflammatory cells in the body. Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a cysteine protease that bridges innate and adaptive immune responses in allergic inflammation. MALT1 protease inhibition is a potential strategy for controlling IgE-mediated allergic disease. P. niruri is a medicinal plant with anti-allergic properties. Objective: This study aimed to evaluate the anti-allergic activity of P. niruri secondary metabolites against MALT1 protease through in silico approach. Method: Physicochemical properties and drug-likeness evaluation were determined using SwissADME. The toxicity properties prediction was analysed using pkCSM. AutoDock Vina was used to evaluate the best binding energy of the compounds against the receptor (PDB ID: 3V4O and 4I1R). Visualisation was obtained using Biovia discovery studio visualiser. Result: Docking analysis showed that ten of 21 compounds have lower binding affinity than the native ligand and reference drugs at the 3V4O receptor. At the 4I1R receptor, only three compounds have a lower binding affinity than its native ligand, but only one compound has a lower binding affinity than all reference drugs. Conclusion: Several P. niruri secondary metabolites were potentially predicted to be developed as MALT1 protease inhibitory agents.

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Phyllanthin and hypophyllanthin, the isolated compounds of Phyllanthus niruri inhibit protein receptor of corona virus (COVID-19) through in silico approach

Cited by 15 publications

References 31 publications

CLEC5A expression can be triggered by spike glycoprotein and may be a potential target for COVID‐19 therapy

CLEC5A expression can be triggered by spike glycoprotein and may be a potential target for COVID‐19 therapy

Cytotoxic and chemomodulatory effects of Phyllanthus niruri in MCF-7 and MCF-7ADR breast cancer cells

Investigating the anti-allergic activity of Phyllanthus niruri via MALT1 protease inhibition: An in silico approach

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