Urtica dioica Agglutinin: A plant protein candidate for inhibition of SARS-COV-2 receptor-binding domain for control of Covid19 Infection

Sabzian‐Molaei, Fatemeh; Khalili, Mohammad Ali Nasiri; Sabzian-Molaei, Mohammad; Shahsavarani, Hosein; Pour, Alireza Fattah; Rad, Ahmad Molaei; Hadi, Amin

doi:10.1371/journal.pone.0268156

Cited by 14 publications

(12 citation statements)

References 29 publications

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“…Via molecular docking it has been proposed that UDA specifically interacts with N -linked glycans on the RBD ( Lokhande et al., 2022 ; Sabzian-Molaei et al., 2022 ). However, our SPR data indicate that UDA is not directly interfering with binding of the RBD to ACE2, arguing for a post-attachment effect of UDA.…”

Section: Discussionmentioning

confidence: 99%

Carbohydrate-binding protein from stinging nettle as fusion inhibitor for SARS-CoV-2 variants of concern

Vanhulle

D’huys²,

Provinciael³

et al. 2022

Front. Cell. Infect. Microbiol.

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Urtica dioica agglutinin (UDA) is a carbohydrate-binding small monomeric protein isolated from stinging nettle rhizomes. It inhibits replication of a broad range of viruses, including coronaviruses, in multiple cell types, with appealing selectivity. In this work, we investigated the potential of UDA as a broad-spectrum antiviral agent against SARS-CoV-2. UDA potently blocks transduction of pseudotyped SARS-CoV-2 in A549.ACE2+-TMPRSS2 cells, with IC50 values ranging from 0.32 to 1.22 µM. Furthermore, UDA prevents viral replication of the early Wuhan-Hu-1 strain in Vero E6 cells (IC50 = 225 nM), but also the replication of SARS-CoV-2 variants of concern, including Alpha, Beta and Gamma (IC50 ranging from 115 to 171 nM). In addition, UDA exerts antiviral activity against the latest circulating Delta and Omicron variant in U87.ACE2+ cells (IC50 values are 1.6 and 0.9 µM, respectively). Importantly, when tested in Air-Liquid Interface (ALI) primary lung epithelial cell cultures, UDA preserves antiviral activity against SARS-CoV-2 (20A.EU2 variant) in the nanomolar range. Surface plasmon resonance (SPR) studies demonstrated a concentration-dependent binding of UDA to the viral spike protein of SARS-CoV-2, suggesting interference of UDA with cell attachment or subsequent virus entry. Moreover, in additional mechanistic studies with cell-cell fusion assays, UDA inhibited SARS-CoV-2 spike protein-mediated membrane fusion. Finally, pseudotyped SARS-CoV-2 mutants with N-glycosylation deletions in the S2 subunit of the spike protein remained sensitive to the antiviral activity of UDA. In conclusion, our data establish UDA as a potent fusion inhibitor for the current variants of SARS-CoV-2.

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Section: Discussionmentioning

confidence: 99%

Carbohydrate-binding protein from stinging nettle as fusion inhibitor for SARS-CoV-2 variants of concern

Vanhulle

D’huys²,

Provinciael³

et al. 2022

Front. Cell. Infect. Microbiol.

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“…The coronavirus SARS-CoV-2 has been, for the past two years, the focus of the scientific community as well as the general public, and its virology, epidemiology, etiology, diagnosis and treatment are extensively well documented [ 8 ]. The scientific studies that focused on the glycolprofiling of the SARS-CoV-2 virus were mostly in vitro and did not employ the lectin-based techniques or the crude nasopharyngeal samples from the positive patients [ 12 ]. Herein, we wanted to investigate the in situ lectin–glycan interactions of viral glycoproteins and broaden the use of GLYcoPROFILE ® technology that has already been well established for several biotechnological applications [ 14 , 15 , 16 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…Structurally, the SARS-CoV-2 virus contains an envelope that exhibits glycoproteins such as spike (S-protein) and membrane (M-protein) proteins. These proteins, especially S-proteins, have the central role in viral pathogenesis and attachment to the angiotensin-converting enzyme 2 (ACE2), mainly expressed in the host lung’s epithelial cells [ 11 , 12 ]. The presence of glycoproteins in the viral envelope of SARS-CoV-2 also opens a wide range of possibilities for the application of carbohydrate-binding agents in clinical analysis, such as lectins, that recognize specific types of carbohydrates residues [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Lectin Analysis of SARS-CoV-2-Positive Nasopharyngeal Samples Using GLYcoPROFILE® Technology Platform

Seničar¹,

Roubinet²,

Daniellou

et al. 2022

Diagnostics

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Nasopharyngeal samples are currently accepted as the standard diagnostic samples for nucleic acid amplification testing and antigenic testing for the SARS-CoV-2 virus. In addition to the diagnostic capacity of SARS-CoV-2-positive crude nasopharyngeal samples, their qualitative potential for direct glycan-specific analysis, in order to uncover unique glycol profiles, was assessed. In this study we provide glycan characterization of SARS-CoV-2-positive and -negative nasopharyngeal samples directly from lectin interactions. Although with limited throughput, this study evaluated the clinical sensitivity and specificity of the GLYcoPROFILE® technology platformon45crude nasopharyngeal samples collected between November 2020 and April 2022. Each GLYcoPROFILE® of 39 SARS-CoV-2-positive samples was compared toglycoprofiling on a panel of 10 selected lectins and the results were paralleled with SARS-CoV-2-negative samples’ results. The GLYcoPROFILE® showed a clear distinction between positive and negative samples with WFA, GSL-II, PHA-L (GlcNAc-specific) and BPA (GalNAc-specific) highlighted as relevant lectins in SARS-CoV-2-positive samples. In addition, a significant, positive statistical correlation was found for these lectins (p < 0.01).

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“…The v‐rescale algorithm was used to keep the temperature constant, and the Berendsen algorithm was used to keep the pressure constant. First, NVT was performed to stabilize the temperature at 300 K for 1 ns, and NPT was performed to stabilize the pressure at 1 bar for 1 ns [15] . Finally, 100 ns final simulation was performed.…”

Section: Methodsmentioning

confidence: 99%

“…First, NVT was performed to stabilize the temperature at 300 K for 1 ns, and NPT was performed to stabilize the pressure at 1 bar for 1 ns. [15] Finally, 100 ns final simulation was performed. After that, the binding free energy of the complexes was calculated in PRODIGY; Protein Binding Energy Prediction (PRODIGY) is a collection of web services designed to predict binding affinity in biological complexes and identify biological interfaces from crystallographic structures.…”

Section: Chemistryselectmentioning

confidence: 99%

Antiviral Effect of Saffron Compounds on the GP120 of HIV‐1: an In Silico Study

et al. 2022

Self Cite

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Since most anti-HIV-1 drugs must penetrate host cells to prevent viral replication, developing viral inhibitors as drugs is essential because they inactivate viruses before binding to host cells. gp120 HIV-1 surface glycoprotein, which has a role in the first stages of HIV-1 infection and entrance of the virus to the cell, is one of the proper molecules for targeted therapy. The phenylalanine-43 cavity located protectively between the inner and outer domains of gp120 of several virus variants has been an attractive medical target for its interaction with CD4. Contrary to industrial drugs, saffron's bioactivity has recently been noticed due to its bio-accessibility and bioavailability, low toxicity, and ease of production. Due to its carotenoid content, this study examined, for the first time, the main components of saffron (Crocin, Picrocrocin, Safranal and Crocetin) for their ability to inhibit viral-cellular membrane fusion and inactivate cell-free HIV-1.The dockings were performed using Autodock Vina Software to study the interactions between the saffron compounds mentioned above with gp120 and CD4 separately. Hence, the dockings were done using Autodock Vina software. The results showed that Crocin and Picrocrocin compounds attach to the protected Phe43 Cavity and Asp368, Trp427, and Ile371 (binding site) of gp120. To confirm the stability, the best complexes of docking were studied using molecular dynamic simulation (via Gromacs 2020.2). It was observed that Crocin keeps its attachment for 100 ns of the simulation, but Picrocrocin detaches. In the end, the binding affinity of Crocin and gp120 was calculated in the 100 snapshots of the last 10 ns of simulations using PRODIGY, which was À 10.3 kcal/mol. Finally, Crocin was suggested as a treatment for AIDS. Based on our atomic-level studies, we have determined that Crocin can stably bind to gp120 but not to human CD4 + T cells in the absence of HIV-1.

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Urtica dioica Agglutinin: A plant protein candidate for inhibition of SARS-COV-2 receptor-binding domain for control of Covid19 Infection

Cited by 14 publications

References 29 publications

Carbohydrate-binding protein from stinging nettle as fusion inhibitor for SARS-CoV-2 variants of concern

Carbohydrate-binding protein from stinging nettle as fusion inhibitor for SARS-CoV-2 variants of concern

Lectin Analysis of SARS-CoV-2-Positive Nasopharyngeal Samples Using GLYcoPROFILE® Technology Platform

Antiviral Effect of Saffron Compounds on the GP120 of HIV‐1: an In Silico Study

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