Cytoplasmic tail determines the membrane trafficking and localization of SARS-CoV-2 spike protein DOI Creative Commons

Qinlin Li,

Yihan Liu, Leiliang Zhang

et al.

Frontiers in Molecular Biosciences, Journal Year: 2022, Volume and Issue: 9

Published: Sept. 26, 2022

The spike (S) glycoprotein of SARS-CoV-2 mediates viral entry through associating with ACE2 on host cells. Intracellular trafficking and palmitoylation S protein are required for its function. short cytoplasmic tail plays a key role in the intracellular trafficking, which contains binding site proteins such as COPI, COPII SNX27. This also sites protein. Protein modification could be catalyzed by family zinc finger DHHC domain-containing palmitoyltransferases (ZDHHCs). membrane location facilitate surface expression assembly progeny virions. In this review, we summarize function transportation localization. relies pathways to life cycle SARS-CoV-2, meanwhile it interfere transport pathways. interplay between partially explain acute symptoms or Long-COVID complications multiple organs COVID-19 patients.

Language: Английский

Identification of SARS-CoV-2 Spike Palmitoylation Inhibitors That Results in Release of Attenuated Virus with Reduced Infectivity DOI Creative Commons
Ahmed Ramadan, Karthick Mayilsamy,

Andrew R. McGill

et al.

Viruses, Journal Year: 2022, Volume and Issue: 14(3), P. 531 - 531

Published: March 4, 2022

The spike proteins of enveloped viruses are transmembrane glycoproteins that typically undergo post-translational attachment palmitate on cysteine residues the cytoplasmic facing tail protein. role protein palmitoylation in virus biogenesis and infectivity is being actively studied as a potential target novel antivirals. Here, we report first five C-terminal cysteine-rich domain SARS-CoV-2 S indispensable for infection, palmitoylation-deficient mutants defective membrane fusion. DHHC9 palmitoyltransferase interacts with palmitoylates ER Golgi knockdown results reduced fusion infection SARS-CoV-2. Two bis-piperazine backbone-based inhibitors inhibit resulting progeny virion particles released infection. This establishes these new intervention strategies against

Language: Английский

Citations

38
Lipid and Lipidation in Membrane Fusion DOI Open Access

Avijit Sardar,

Nikesh Dewangan,

Bishvanwesha Panda

et al.

The Journal of Membrane Biology, Journal Year: 2022, Volume and Issue: 255(6), P. 691 - 703

Published: Sept. 14, 2022

Language: Английский

Citations

33
Unraveling the role of the nucleocapsid protein in SARS-CoV-2 pathogenesis: From viral life cycle to vaccine development DOI
Yousra A. El‐Maradny,

Moustafa A. Badawy,

Kareem I. Mohamed

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 279, P. 135201 - 135201

Published: Aug. 30, 2024

Language: Английский

Citations

7
Protein Palmitoylation Modification During Viral Infection and Detection Methods of Palmitoylated Proteins DOI Creative Commons
Xiaoling Li,

Lingyi Shen,

Zhao Xu

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2022, Volume and Issue: 12

Published: Jan. 27, 2022

Protein palmitoylation—a lipid modification in which one or more cysteine thiols on a substrate protein are modified to form thioester with palmitoyl group—is significant post-translational biological process. This process regulates the trafficking, subcellular localization, and stability of different proteins cells. Since palmitoylation participates various processes, it is related occurrence development multiple diseases. It has been well evidenced that whose functions palmitoylation-dependent directly involved key proteins’ palmitoylation/depalmitoylation cycle may be potential source novel therapeutic drugs for Many researchers have reported proteins, crucial host-virus interactions during viral infection. Quite few explorations focused figuring out whether targeting acylation host might strategy combat All these remarkable achievements made technological advances. paper gives an overview infection methods palmitoylated detection. Future challenges developments proposed.

Language: Английский

Citations

23
The life cycle and enigmatic egress of coronaviruses DOI Creative Commons
Kristian Prydz, Jaakko Saraste

Molecular Microbiology, Journal Year: 2022, Volume and Issue: 117(6), P. 1308 - 1316

Published: April 18, 2022

There has been considerable recent interest in the life cycle of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), causative agent Covid-19 pandemic. Practically every step CoV replication-from cell attachment and uptake via genome replication expression to virion assembly considered as a specific event that potentially could be targeted by existing or novel drugs. Interference with cellular egress progeny viruses also adopted possible therapeutic strategy; however, situation is complicated fact there no broad consensus on how CoVs find their way out host cells. The viral nucleocapsid, consisting genomic RNA complexed nucleocapsid proteins obtains membrane envelope during virus budding into lumen intermediate compartment (IC) at endoplasmic reticulum (ER)-Golgi interface. From here, several alternative routes for extracellular release have proposed. Strikingly, studies shown infection leads disassembly Golgi ribbon mobilization compartments protein machineries are known promote Golgi-independent trafficking surface. Here, we discuss special focus different pathways egress.

Language: Английский

Citations

20
Palmitoylation of SARS-CoV-2 Envelope protein is central to virus particle formation DOI
Z. W. Wang,

Manman Qiu,

Yue Ji

et al.

Journal of Virology, Journal Year: 2024, Volume and Issue: 98(10)

Published: Sept. 17, 2024

ABSTRACT The Envelope (E) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an integral structural in the virus particles. However, its role assembly virions and underlying molecular mechanisms are yet to be elucidated, including whether function E regulated by post-translational modifications. In present study, we report that SARS-CoV-2 palmitoylated at C40, C43, C44 palmitoyltransferases zDHHC3, 6, 12, 15, 20. Mutating these three cysteines serines (C40/43/44S) reduced stability protein, decreased interaction with proteins Spike, Membrane, Nucleocapsid, thereby inhibited production virus-like particles (VLPs) VLP-mediated luciferase transcriptional delivery. Specifically, C40/43/44S mutation density VLPs. Collectively, results demonstrate palmitoylation vital for IMPORTANCE this systematically examined biochemistry demonstrated required particle (VLP) maintaining normal density. These suggest central proper morphogenesis VLPs densities viral infectivity. This study presents a significant advancement understanding how assembling supports palmitoyl acyltransferases can potential therapeutic targets development inhibitors.

Language: Английский

Citations

4
ZDHHC3-LYPLA1 regulates PRRSV-2 replication through reversible palmitoylation DOI
Huiyuan Jing, Ying Liu,

Yu-gang Song

et al.

Veterinary Microbiology, Journal Year: 2025, Volume and Issue: 301, P. 110368 - 110368

Published: Jan. 5, 2025

Language: Английский

Citations

0
Sequences in the Cytoplasmic Tail Contribute to the Intracellular Trafficking and the Cell Surface Localization of SARS-CoV-2 Spike Protein DOI Creative Commons
Evgeniya E. Burkova, Irina A. Bakhno

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 280 - 280

Published: Feb. 14, 2025

Spike protein is a surface glycoprotein of the SARS-CoV-2 coronavirus, providing interaction coronavirus with angiotensin-converting enzyme 2 (ACE2) on host cell. The cytoplasmic tail S plays an important role in intracellular transport and translocation to plasma membrane. domain contains binding sites for COPI, COPII, SNX27, which are required trafficking this glycoprotein. In addition, S-palmitoylation sites. increases hydrophobicity by regulating its has signaling sequence that provides ERM family proteins, may mediate communication between cell membrane actin cytoskeleton. This review examines Understanding these processes necessary not only development vaccines based mRNA or adenovirus vectors encoding full-length spike (S) protein, but also therapy new infection (COVID-19).

Language: Английский

Citations

0
Perturbation of de novo lipogenesis hinders MERS-CoV assembly and release, but not the biogenesis of viral replication organelles DOI Creative Commons
Maria Soultsioti, Anja W. M. de Jong,

N. Blomberg

et al.

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

Published: Feb. 20, 2025

ABSTRACT Coronaviruses hijack host cell metabolic pathways and resources to support their replication. They induce extensive endomembrane remodeling generate viral replication organelles exploit membranes for assembly budding of enveloped progeny virions. Because the overall significance membranes, we sought gain insight into role factors involved in lipid metabolism cells infected with Middle East respiratory syndrome coronavirus (MERS-CoV). We employed a single-cycle infection approach combination pharmacological inhibitors, biochemical assays, lipidomics, light electron microscopy. Pharmacological inhibition acetyl-CoA carboxylase (ACC) fatty acid synthase (FASN), key de novo biosynthesis, led pronounced MERS-CoV particle release. Inhibition ACC profound switch Huh7 cells, altering lipidomic profile inducing lipolysis. However, despite changes induced by inhibitor, biogenesis remained unaffected. Instead, appeared affect trafficking post-translational modifications envelope proteins. Electron microscopy revealed an accumulation nucleocapsids early stages, indicating that is adversely impacted inhibition. Notably, palmitoylation resulted similar effects, while supplementation exogenous palmitic reversed compound’s inhibitory possibly reflecting crucial need spike proteins virus assembly. IMPORTANCE (MERS-CoV) etiological agent zoonotic disease limited transmissibility between humans. still considered high-priority pathogen closely monitored WHO due its high lethality rate around 35% laboratory-confirmed infections. Like other positive-strand RNA viruses, relies on cell’s endomembranes various stages cycle. spite this general reliance metabolism, mechanistic insights are very limited. In our study, show (ACC), enzyme biosynthesis pathway, significantly disrupts without exerting negative effect organelles. Furthermore, study highlights potential as target development host-directed antiviral therapeutics against coronaviruses.

Language: Английский

Citations

0
Tradeoffs between proliferation and transmission in virus evolution– insights from evolutionary and functional analyses of SARS-CoV-2 DOI Creative Commons
Jui‐Hung Tai,

Ding-Chin Lee,

Hsin-Fu Lin

et al.

Virology Journal, Journal Year: 2025, Volume and Issue: 22(1)

Published: April 19, 2025

Language: Английский

Citations

0