Inhibition of hostN-myristoylation compromises the infectivity of SARS-CoV-2 due to Golgi-bypassing egress from lysosomes and endoplasmic reticulum DOI Creative Commons

Saber H. Saber,

Mohammed R. Shaker,

Julian Sng

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: March 3, 2023

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused the disease 2019 (COVID-19) pandemic, remains a global health concern despite vaccines, neutralizing antibodies, and antiviral drugs. Emerging mutations can reduce effectiveness of these treatments, suggesting that targeting host cell factors may be valuable alternative. N -myristoyltransferases (NMT) are essential enzymes for protein -myristoylation, affecting stability, interaction, localization, function numerous proteins. We demonstrate selective inhibition NMT decreases SARS-CoV-2 infection by 90% in human lung primary nasal epithelial cells, choroid plexus-cortical neuron organoids. does not affect viral entry, replication or release, but impairs maturation incorporation envelope proteins into newly assembled virions, leading to compromised infectivity released virions. The triggers Golgi-bypassing pathway progeny virion egress, occurs through endoplasmic reticulum lysosomal intermediates.

Language: Английский

Frontier applications of retinal nanomedicine: progress, challenges and perspectives DOI Creative Commons

Zhimin Tang,

Fuxiang Ye, Ni Ni

et al.

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 25, 2025

The human retina is a fragile and sophisticated light-sensitive tissue in the central nervous system. Unhealthy retinas can cause irreversible visual deterioration permanent vision loss. Effective therapeutic strategies are restricted to treatment or reversal of these conditions. In recent years, nanoscience nanotechnology have revolutionized targeted management retinal diseases. Pharmaceuticals, theranostics, regenerative medicine, gene therapy, prostheses indispensable for interventions been significantly advanced by nanomedical innovations. Hence, this review presents novel insights into use versatile nanomaterial-based nanocomposites frontier applications, including non-invasive drug delivery, theranostic contrast agents, nanoagents, stem cell-based optogenetics prostheses, which mainly reported within last 5 years. Furthermore, progress, potential challenges, future perspectives field highlighted discussed detail, may shed light on clinical translations ultimately, benefit patients with disorders.

Language: Английский

Citations

0
Compartmentalization of proteasomes in lipid rafts and exosomes: unveiling molecular interactions in vaping-related cellular processes DOI
Rasheedunnisa Begum,

D Mutyala,

Swapna Thota

et al.

Archives of Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: April 27, 2025

Language: Английский

Citations

0
Protein lipidation in the tumor microenvironment: enzymology, signaling pathways, and therapeutics DOI Creative Commons

Mengke Xu,

Bo Xu

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: May 7, 2025

Abstract Protein lipidation is a pivotal post-translational modification that increases protein hydrophobicity and influences their function, localization, interaction network. Emerging evidence has shown significant roles of in the tumor microenvironment (TME). However, comprehensive review this topic lacking. In review, we present an integrated in-depth literature context TME. Specifically, focus on three major modifications: S- prenylation, palmitoylation, N- myristoylation. We emphasize how these modifications affect oncogenic signaling pathways complex interplay between cells surrounding stromal immune cells. Furthermore, explore therapeutic potential targeting mechanisms cancer treatment discuss prospects for developing novel anticancer strategies disrupt lipidation-dependent pathways. By bridging with dynamics TME, our provides insights into relationship them drives initiation progression.

Language: Английский

Citations

0
哺乳动物细胞蛋白质折叠和内质网相关降解的研究进展 DOI
Hong Cao, Xuchang Zhou, Bowen Xu

et al.

Journal of Zhejiang University SCIENCE B, Journal Year: 2024, Volume and Issue: 25(3), P. 212 - 232

Published: March 1, 2024

Language: Английский

Citations

2
Precise control of transmembrane current via regulating bionic lipid membrane composition DOI Creative Commons
Zhiwei Shang, Jing Zhao, Mengyu Yang

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(35)

Published: Aug. 30, 2024

The transport of ions through biological ion channels is regulated not only by their structural characteristics but also the composition phospholipid membrane, which serves as a carrier for nanochannels. Inspired modulation currents lipid membrane composition, exemplified activation K

Language: Английский

Citations

2
Regulation of Transmembrane Current through Modulation of Biomimetic Lipid Membrane Composition DOI

Zhiwei Shang,

Jing Zhao, Mengyu Yang

et al.

Faraday Discussions, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 23, 2024

Ion transport through biological channels is influenced not only by the structural properties of themselves but also composition phospholipid membrane, which acts as a scaffold for these nanochannels. Drawing inspiration from how lipid membrane modulates ion currents, seen in activation K

Language: Английский

Citations

0
Targeting n-myristoyltransferases promotes a pan-Mammarenavirus inhibition through the degradation of the Z matrix protein DOI Creative Commons
Xavier Carnec, Virginie Borges-Cardoso, Stéphanie Reynard

et al.

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(12), P. e1012715 - e1012715

Published: Dec. 3, 2024

Several Old World and New Mammarenavirus are responsible for hemorrhagic fever in humans. These enveloped viruses have a bi-segmented ambisense RNA genome that encodes four proteins. All identified to date share common dependency on myristoylation: the addition of C14 myristic acid N-terminal G2 residue two their The myristoylation Z matrix protein is required viral particle budding, while signal peptide envelope glycoproteins important entry mechanism. Using Mopeia virus as model, we characterized interaction with N-Myristoyltransferases (NMT) 1 2, enzymes mammals. While both were capable interact Z, showed only NMT1 was production progeny, endogenous expression NMT2 being insufficient make up its absence. high affinity inhibitors NMTs, IMP1088 DDD85646, demonstrated strong, dose dependent specific inhibition at nanomolar range all tested, including highly pathogenic Lassa, Machupo, Junin Lujo viruses. Mechanistically, DDD85646 blocked between preventing further formation, egress spread. Unexpectedly, found devoid myristate, despite fully translated, did not accumulate other proteins infected cells but instead degraded proteasome- autophagy-independent manner. molecules represent new broad-spectrum class against .

Language: Английский

Citations

0
Inhibition of hostN-myristoylation compromises the infectivity of SARS-CoV-2 due to Golgi-bypassing egress from lysosomes and endoplasmic reticulum DOI Creative Commons

Saber H. Saber,

Mohammed R. Shaker,

Julian Sng

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: March 3, 2023

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused the disease 2019 (COVID-19) pandemic, remains a global health concern despite vaccines, neutralizing antibodies, and antiviral drugs. Emerging mutations can reduce effectiveness of these treatments, suggesting that targeting host cell factors may be valuable alternative. N -myristoyltransferases (NMT) are essential enzymes for protein -myristoylation, affecting stability, interaction, localization, function numerous proteins. We demonstrate selective inhibition NMT decreases SARS-CoV-2 infection by 90% in human lung primary nasal epithelial cells, choroid plexus-cortical neuron organoids. does not affect viral entry, replication or release, but impairs maturation incorporation envelope proteins into newly assembled virions, leading to compromised infectivity released virions. The triggers Golgi-bypassing pathway progeny virion egress, occurs through endoplasmic reticulum lysosomal intermediates.

Language: Английский

Citations

0