The host mannose-6-phosphate pathway and viral infection DOI Creative Commons

Qincheng Liu,

Weiqi Wang,

Liwei Xu

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 31, 2024

Viruses, despite their simple structural composition, engage in intricate and complex interactions with hosts due to parasitic nature. A notable demonstration of viral behavior lies exploitation lysosomes, specialized organelles responsible for the breakdown biomolecules clearance foreign substances, bolster own replication. The man-nose-6-phosphate (M6P) pathway, crucial facilitating proper transport hydrolases into lysosomes promoting lysosome maturation, is frequently exploited manipulation support Recently, discovery lysosomal enzyme trafficking factor (LYSET) as a pivotal regulator within M6P pathway has introduced fresh perspective on interplay between entry host factors. This groundbreaking revelation illuminates unexplored dimensions these interactions. In this review, we endeavor provide thorough overview its factors during infection. By consolidating current understanding field, our objective establish valuable reference development antiviral drugs that selectively target pathway.

Language: Английский

The HN protein of Newcastle disease virus induces cell apoptosis through the induction of lysosomal membrane permeabilization DOI Creative Commons
Yu Chen, Shanshan Zhu, Tianxing Liao

et al.

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(2), P. e1011981 - e1011981

Published: Feb. 14, 2024

Lysosomes are acidic organelles that mediate the degradation and recycling of cellular waste materials. Damage to lysosomes can cause lysosomal membrane permeabilization (LMP) trigger different types cell death, including apoptosis. Newcastle disease virus (NDV) naturally infect most birds. Additionally, it serves as a promising oncolytic known for its effective infection tumor cells induction intensive apoptotic responses. However, involvement in NDV-induced apoptosis remains poorly understood. Here, we demonstrate NDV profoundly triggers LMP, leading translocation cathepsin B D subsequent mitochondria-dependent various avian cells. Notably, released exacerbate LMP by inducing generation reactive oxygen species. uncover viral Hemagglutinin neuraminidase (HN) protein induces deglycosylation lysosome-associated 1 (LAMP1) LAMP2 dependent on sialidase activity, which finally contributes Overall, our findings elucidate role provide novel insights into function HN during innovative approaches development NDV-based agents.

Language: Английский

Citations

11
Roles of host proteases in the entry of SARS-CoV-2 DOI Creative Commons

Alexandria Zabiegala,

Yunjeong Kim, Kyeong‐Ok Chang

et al.

Animal Diseases, Journal Year: 2023, Volume and Issue: 3(1)

Published: April 25, 2023

Abstract The spike protein (S) of SARS-CoV-2 is responsible for viral attachment and entry, thus a major factor host susceptibility, tissue tropism, virulence pathogenicity. S divided with S1 S2 region, the contains receptor-binding domain (RBD), while hydrophobic fusion entry into cell. Numerous proteases have been implicated in activation through various cleavage sites. In this article, we review including furin, trypsin, transmembrane protease serine 2 (TMPRSS2) cathepsins S. Many betacoronaviruses polybasic residues at S1/S2 site which subjected to by furin. facilitates more assessable RBD receptor ACE2, binding triggers further conformational changes exposure S2’ such as type II (TTPRs) TMPRSS2. presence TMPRSS2 on target cells, can utilize direct route envelope cellular membrane. absence TMPRSS2, enter cells via endosomes where multiple cleave successful entry. Additional involved were discussed. This article also includes roles 3C-like inhibitors inhibitory activity against cathepsin L SARS-CoV-2, discussed dual virus replication.

Language: Английский

Citations

19
Cathepsin-Targeting SARS-CoV-2 Inhibitors: Design, Synthesis, and Biological Activity DOI Open Access

Philipp Flury,

Julian Breidenbach, Nadine Krüger

et al.

ACS Pharmacology & Translational Science, Journal Year: 2024, Volume and Issue: 7(2), P. 493 - 514

Published: Jan. 19, 2024

Cathepsins (Cats) are proteases that mediate the successful entry of SARS-CoV-2 into host cells. We designed and synthesized a tailored series 21 peptidomimetics evaluated their inhibitory activity against human cathepsins L, B, S. Structural diversity was realized by combinations different C-terminal warhead functions N-terminal capping groups, while central Leu-Phe fragment maintained. Several compounds were identified as promising cathepsin L S inhibitors with

Language: Английский

Citations

4
Aprotinin (II): Inhalational Administration for the Treatment of COVID-19 and Other Viral Conditions DOI Open Access
Juan Fernando Padín, José Manuel Pérez‐Ortiz, Francisco Javier Redondo Calvo

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7209 - 7209

Published: June 29, 2024

Aprotinin is a broad-spectrum inhibitor of human proteases that has been approved for the treatment bleeding in single coronary artery bypass surgery because its potent antifibrinolytic actions. Following outbreak COVID-19 pandemic, there was an urgent need to find new antiviral drugs. good candidate therapeutic repositioning as drug and treating symptomatic processes characterise viral respiratory diseases, including COVID-19. This due strong pharmacological ability inhibit plethora host used by viruses their infective mechanisms. The allow cleavage conformational change proteins make up capsid, thus enable them anchor themselves recognition target epithelial cell. In addition, activation these initiates inflammatory process triggers infection. attraction not only pharmacodynamic characteristics but also possibility administration inhalation route, avoiding unwanted systemic effects. This, together with low cost (≈2 Euro/dose), makes it reach countries lower economic means. this article, we will discuss pharmacodynamic, pharmacokinetic, toxicological aprotinin administered route; analyse main advances our knowledge medication; future directions should be taken research order reposition medication therapeutics.

Language: Английский

Citations

4
Broadening Horizons: Exploring the Cathepsin Family as Therapeutic Targets for Alzheimer's Disease DOI Creative Commons
Xiaohui Liu, Xiaotong Liu,

Yue Wu

et al.

Aging and Disease, Journal Year: 2024, Volume and Issue: unknown, P. 0 - 0

Published: Jan. 1, 2024

Alzheimer's disease (AD) is an intricate neurodegenerative disorder characterized by the accumulation of misfolded proteins, including beta-amyloid (Aβ) and tau, leading to cognitive decline. Despite decades research, precise mechanisms underlying its onset progression remain elusive. Cathepsins are a family lysosomal enzymes that play vital roles in cellular processes, protein degradation regulation immune responses. Emerging evidence suggests cathepsins may be involved AD pathogenesis. can influence activation microglia astrocytes, resident cells brain. However, cathepsin dysfunction lead notably Aβ tau. In addition, dysregulated activity induce exaggerated response, promoting chronic inflammation neuronal patients with AD. By unraveling classification, functions, AD's pathogenesis, this review sheds light on their involvement devastating disease. Targeting could promising novel approach for mitigating pathological processes contribute AD, providing new avenues treatment prevention.

Language: Английский

Citations

4
Non-Canonical, Extralysosomal Activities of Lysosomal Peptidases in Physiological and Pathological Conditions: New Clinical Opportunities for Cancer Therapy DOI Creative Commons

Ryan Conesa-Bakkali,

Macarena Morillo‐Huesca, Jonathan Martínez‐Fábregas

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(2), P. 68 - 68

Published: Jan. 7, 2025

Lysosomes are subcellular compartments characterised by an acidic pH, containing ample variety of acid hydrolases involved in the recycling biopolymers. Among these hydrolases, lysosomal proteases have merely been considered as end-destination responsible for digestion waste proteins, trafficked to compartment through autophagy and endocytosis. However, recent reports started unravel specific roles regulation initially unexpected biological processes, both under physiological pathological conditions. Furthermore, some no longer restricted compartment, more novel non-canonical, extralysosomal targets being identified. Currently, accepted play key functions extracellular milieu, attached plasma membrane even cytosolic nuclear cell. Under conditions, proteases, activities, linked cell differentiation, gene expression, division. cancer, mostly their activities cytosol nuclei cells. In this review, we aim provide a comprehensive summary our current knowledge about extralysosomal, non-canonical with particular interest that could potentially offer new opportunities clinical intervention.

Language: Английский

Citations

0
Transcriptional Atlas of Daphnia Magna DOI
Lev Y. Yampolsky,

Ishaan Dua

Published: Jan. 1, 2025

Language: Английский

Citations

0
Exploring the Link between Plasma Cathepsins and Covid-19: A Bidirectional Mendelian Randomization Analysis of Susceptibility and Severity DOI
M Miao,

You-Lan Lei,

Huiqing Qiu

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
Nucleocapsid Protein of SARS-CoV-2 Upregulates RANTES Expression in A172 Glioblastoma Cells DOI Creative Commons
Bakhytgul Gadilgereyeva,

Zhanar Kunushpayeva,

M. B. Abdrakhmanova

et al.

Molecules, Journal Year: 2025, Volume and Issue: 30(5), P. 1066 - 1066

Published: Feb. 26, 2025

SARS-CoV-2, the pathogenic virus that induces COVID-19 disease, contains four structural proteins in its virion. The nucleocapsid (N) protein is one of play a crucial role assembly viral RNA into ribonucleoprotein. In addition, N contributes to pathogenesis. One functions attributed triggering cytokine release by lung epithelial cells, macrophages, and monocytes. This study addresses cellular effects SARS-CoV-2 on cells glial origin. We report upregulation RANTES chemokine A172 glioblastoma at both mRNA levels response exposure protein. did not have an effect cell viability migration.

Language: Английский

Citations

0
Cathepsins in cellular entry of human pathogenic viruses DOI Creative Commons

Tejal Pathak,

S. C. Pal,

Indranil Banerjee

et al.

Journal of Virology, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

ABSTRACT In the life cycle of a virus, host cell entry represents first step that virus needs to undertake gain access interior for replication. Once attaches itself its target receptor, it activates endogenous cellular responses and exploits factors internalization, fusion, genome release. Among critically contribute viral processes are cathepsins, which most abundant endo/lysosomal proteases with diverse physiological functions. This review summarizes previous findings on how different cathepsins human pathogenic viruses, focusing their specific roles in both enveloped non-enveloped RNA viruses. A comprehensive knowledge functions will provide valuable insights into molecular mechanisms underlying infections can be useful development new antiviral strategies.

Language: Английский

Citations

0