Human Intestinal Defensin 5 Inhibits SARS-CoV-2 Invasion by Cloaking ACE2

Wang, Cheng; Wang, Shaobo; Li, Daixi; Wei, Dong‐Qing; Zhao, Jinghong; Wang, Junping

doi:10.1053/j.gastro.2020.05.015

Cited by 121 publications

(140 citation statements)

References 13 publications

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“…21 The single site mutation makes SARS-CoV-2 three to nine-fold more infectious than the wild type. 22 We analyzed the molecular interaction by BLI and found that D614G-S1 bound to ACE2 at 13.3 nM (Figure 5a), comparable to the affinity of SARS-CoV-2 S1 binding to ACE2, 8 which sustained that the stronger contagiosity of D614G-SARS-CoV-2 than its ancestral form is not due to the enhanced receptor recruitment. 23 Similarly, D614G mutation did not alter the dose-dependent bindings of HEK-293T-hACE2 NPs to SARS-CoV-2 S1 (Figure 5b).…”

Section: Suppression Of Hek-293t-hace2mentioning

confidence: 82%

“…In line with the discrepancy in ACE2 loading, more HEK-293T-hACE2 NPs coated SARS-CoV-2 S1-RBD than HEK-293T NPs (Figure 3a). As SARS-CoV-2 S1 adheres to the surface of sensitive cells including HK-2, 8 we further performed a cell experiment, in which HK-2 cells were exposed to 10 μg mL -1 of SARS-CoV-2 S1.…”

Section: Resultsmentioning

confidence: 99%

“…was adsorbed on HEK-293T-hACE2 NPs (Figure 3d) and the protein adherence was blocked by human defensin 5 (HD5, Figure S2), an endogenous lectin-like peptide capable of binding to and cloaking ACE2. 8 Accordingly, few viral proteins adhered to HK-2 cells after pretreatment with HEK-293T-hACE2 NPs (Figure 3e). (Table S1) including voltage-dependent anion channel (VDAC) 1, VDAC2, and VDAC3…”

Section: Hek-293t Nps Prepared Using the Same Methods Had Comparablementioning

confidence: 98%

“…Additionally, anti-ACE2 serum and human intestinal defensin able to cloak ACE2 we recently reported were efficient to inhibit SARS-CoV-2 invasion, 6,8 indicating that ACE2 is a critical receptor for SARS-CoV-2.…”

mentioning

confidence: 88%

“…7 SARS-CoV-2 S1 binds to ACE2 at a high affinity of 8.02 nM. 8 The cells insensitive to SARS-CoV-2 turn to be susceptible to the virus after transfection with ACE2.…”

mentioning

confidence: 99%

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Membrane Nanoparticles Derived from ACE2-rich Cells Block SARS-CoV-2 Infection

Wang

Chen

et al. 2020

Preprint

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The ongoing COVID-19 epidemic worldwide necessitates the development of novel effective agents against SARS-CoV-2. ACE2 is the main receptor of SARS-CoV-2 S1 protein and mediates viral entry into host cells. Herein, the membrane nanoparticles prepared from ACE2-rich cells are discovered with potent capacity to block SARS-CoV-2 infection. The membrane of human embryonic kidney-239T cell highly expressing ACE2 is screened to prepare nanoparticles. The nanomaterial termed HEK-293T-hACE2 NPs contains 265.1 ng mg−1 of ACE2 on the surface and acts as a bait to trap SARS-CoV-2 S1 in a dose-dependent manner, resulting in reduced recruitment of the viral ligand to host cells. Interestingly, SARS-CoV-2 S1 can translocate to the cytoplasm and affect the cell metabolism, which is also inhibited by HEK-293T-hACE2 NPs. Further studies reveal that HEK-293T-hACE2 NPs can efficiently suppress SARS-CoV-2 S pseudovirions entry into human proximal tubular cells and block viral infection with a low half maximal inhibitory concentration. Additionally, this biocompatible membrane nanomaterial is sufficient to block the adherence of SARS-CoV-2 D614G-S1 mutant to sensitive cells. Our study demonstrates a easy-to-acheive memrbane nano-antagonist for curbing SARS-CoV-2, which enriches the existing antiviral arsenal and provides new possibilities to treat COVID-19. Graphical Table of Contents

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Section: Suppression Of Hek-293t-hace2mentioning

confidence: 82%

Section: Resultsmentioning

confidence: 99%

Section: Hek-293t Nps Prepared Using the Same Methods Had Comparablementioning

confidence: 98%

mentioning

confidence: 88%

“…7 SARS-CoV-2 S1 binds to ACE2 at a high affinity of 8.02 nM. 8 The cells insensitive to SARS-CoV-2 turn to be susceptible to the virus after transfection with ACE2.…”

mentioning

confidence: 99%

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Membrane Nanoparticles Derived from ACE2-rich Cells Block SARS-CoV-2 Infection

Wang

Chen

et al. 2020

Preprint

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Paneth cells and their multiple functions

Barreto

Rattes

Costa

et al. 2022

Cell Biology International

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The small intestine mucosa is lined by specialized cells that form the crypt-villus axis, which expands its surface. Among the six intestinal epithelial cell types, the Paneth cell is located at the base of the crypt, and it contains numerous granules in its cytoplasm, composed of antimicrobial peptides, such as defensins and lysozyme, and growth factors, such as epidermal growth factor, transforming growth factor-α, and Wnt ligands. Together, these elements act in the defense against microorganisms, regulation of intestinal microbiota, maintenance, and regulation of stem cell identity.Pathologies that target Paneth cells can disturb such defense activity, but they also affect the maintenance of the stem cell niche. In that way, Crohn's disease, necrotizing enterocolitis, and graft-versus-host disease promote a reduction of Paneth cell population, and, consequently, secretion of their products into the lumen of the crypts, making the affected organism predisposed to infections and dysbiosis. Additionally, the emergence of new intestinal cells is also decreased. This review aims to address the main characteristics of Paneth cells, highlighting their multiple functions and the importance of their preservation to ensure bowel homeostasis.

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Repurposing fusion inhibitor peptide against SARS‐CoV‐2

et al. 2021

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously evolving. Although several vaccines were approved, this pandemic is still a major threat to public life. Till date, no established therapies are available against SARS-CoV-2. Peptide inhibitors hold great promise for this viral pathogen due to their efficacy, safety, and specificity. In this study, seventeen antiviral peptides which were known to inhibit SARS-CoV-1 are collected and computationally screened against heptad repeat 1 (HR1) of the SARS-CoV-2 spike protein (S2). Out of 17 peptides, Fp13 and Fp14 showed better binding affinity toward HR1 compared to a control peptide EK1 (a modified pan-coronavirus fusion inhibitor) in molecular docking. To explore the time-dependent interactions of the fusion peptide with HR1, molecular dynamics simulation was performed incorporating lipid membrane. During 100 ns MD simulation, structural and energy parameters of Fp13-HR1 and Fp14-HR1 complexes demonstrated lower fluctuations compared to the control EK1-HR1 complex.Furthermore, principal component analysis and free energy landscape study revealed that these two peptides (Fp13 and Fp14) strongly bind to the HR1 with higher affinity than that of control EK1. Tyr917, Asn919, Gln926, lys933, and Gln949 residues in HR1 protein were found to be crucial residues for peptide interaction. Notably, Fp13, Fp14 showed reasonably better binding free energy and hydrogen bond contribution than that of EK1. Taken together, Fp13 and Fp14 peptides may be highly specific for HR1 which can potentially prevent the formation of the fusion core and could be further developed as therapeutics for treatment or prophylaxis of SARS-CoV-2 infection.

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Human Intestinal Defensin 5 Inhibits SARS-CoV-2 Invasion by Cloaking ACE2

Cited by 121 publications

References 13 publications

Membrane Nanoparticles Derived from ACE2-rich Cells Block SARS-CoV-2 Infection

Membrane Nanoparticles Derived from ACE2-rich Cells Block SARS-CoV-2 Infection

Paneth cells and their multiple functions

Repurposing fusion inhibitor peptide against SARS‐CoV‐2

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