A BSL-2 chimeric system designed to screen SARS-CoV-2 E protein ion channel inhibitors DOI Creative Commons
Vashi Negi, Richard Kühn

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

Published: April 30, 2025

ABSTRACT A major hindrance to the identification of new drug targets and large-scale testing or existing compound libraries against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is that research on virus restricted biosafety level 3 (BSL-3) laboratories. In such cases, BSL-2 surrogate systems chimeric attenuated versions are developed for safer, faster, cheaper examination stages life cycle specific targets. this study, we describe a viral system utilizing Sindbis background as tool study one target, SARS-CoV-2 Envelope (E) protein channel activity. This fully conserved between SARS-CoV variants concern (VOCs), except threonine isoleucine mutation in Omicron variant, making E ion domain an attractive antiviral target combination therapy. Using BSL-2-chimeric system, have been able show similar inhibition profiles using inhibitors previously reported E-channel authentic SARS-CoV-2. has potential allow faster initial screening can be useful developing broad-spectrum antivirals proteins. IMPORTANCE Despite its importance infections, no exist activity protein. The highly among variants, it therapies. Research BSL-3 laboratories, creating bottleneck compounds. presents novel bypasses limitation, offering safer approach inhibitors. By replicating more accessible paves way development proteins, potentially expediting discovery life-saving treatments COVID-19 other diseases.

Language: Английский

SARS-CoV-2-Specific Immune Response and the Pathogenesis of COVID-19 DOI Open Access
Evgeni Gusev, Alexey Sarapultsev, Л. В. Соломатина

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(3), P. 1716 - 1716

Published: Feb. 2, 2022

The review aims to consolidate research findings on the molecular mechanisms and virulence pathogenicity characteristics of coronavirus disease (COVID-19) causative agent, severe acute respiratory syndrome 2 (SARS-CoV-2), their relevance four typical stages in development viral infection. These are invasion; primary blockade antiviral innate immunity; engagement virus’s protection against factors adaptive acute, long-term complications COVID-19. invasion stage entails recognition spike protein (S) SARS-CoV-2 target cell receptors, namely, main receptor (angiotensin-converting enzyme 2, ACE2), its coreceptors, potential alternative receptors. presence a diverse repertoire receptors allows infect various types cells, including those not expressing ACE2. During second stage, majority polyfunctional structural, non-structural, extra proteins synthesizes infected cells involved blockage immunity. A high degree redundancy systemic action characterizing these pathogenic overcome at initial invasion. third includes passive active virus from immunity, overcoming barrier function focus inflammation, generalization body. fourth is associated with deployment variants SARS-CoV-2’s ability induce autoimmune autoinflammatory pathways tissue both immunosuppressive hyperergic inflammation critical this

Language: Английский

Citations

225
SARS-CoV-2 E protein: Pathogenesis and potential therapeutic development DOI Creative Commons
Shilin Zhou, Panpan Lv, Mingxue Li

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 159, P. 114242 - 114242

Published: Jan. 11, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a devastating global pandemic, which seriously affected human health worldwide. The discovery of therapeutic agents is extremely urgent, and the viral structural proteins are particularly important as potential drug targets. SARS-CoV-2 envelope (E) protein one main virus, involved in multiple processes virus life cycle directly related to pathogenesis process. In this review, we present amino acid sequence E compare it with other two coronaviruses. We then explored role discussed pathogenic mechanisms that may be in. Next, summarize drugs against discovered current studies. Finally, described possible effects mutation on host. This established knowledge system date, aiming provide theoretical insights for mitigating COVID-19 pandemic future outbreaks.

Language: Английский

Citations

45
The E3 ligase RNF5 restricts SARS-CoV-2 replication by targeting its envelope protein for degradation DOI Creative Commons
Zhaolong Li, Pengfei Hao,

Zhilei Zhao

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Feb. 3, 2023

Abstract The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome 2 (SARS-CoV-2) has a global health crisis; its structural protein envelope (E) is critical for viral entry, budding, production, and induction of pathology which makes it potential target therapeutics against COVID-19. Here, we find that the E3 ligase RNF5 interacts with catalyzes ubiquitination E on 63rd lysine, leading to degradation ubiquitin-proteasome system (UPS). Importantly, RNF5-induced inhibits SARS-CoV-2 replication pharmacological activator Analog-1 alleviates development in mouse infection model. We also found distinctively expressed different age groups patients displaying severity, may be exploited as prognostic marker Furthermore, recognized from various strains SARS-CoV, suggesting targeting broad-spectrum antiviral strategy. Our findings provide novel insights into role UPS antagonizing replication, opens new avenues therapeutic intervention combat COVID-19 pandemic.

Language: Английский

Citations

45
Characterization of the SARS‐CoV‐2 E Protein: Sequence, Structure, Viroporin, and Inhibitors DOI Open Access
Yipeng Cao, Rui Yang, Imshik Lee

et al.

Protein Science, Journal Year: 2021, Volume and Issue: 30(6), P. 1114 - 1130

Published: April 4, 2021

The COVID-19 epidemic is one of the most influential epidemics in history. Understanding impact coronaviruses (CoVs) on host cells very important for disease treatment. SARS-CoV-2 envelope (E) protein a small structural involved many aspects viral life cycle. E promotes packaging and reproduction virus, deletion this weakens or even abolishes virulence. This review aims to establish new knowledge by combining recent advances study comparing it with SARS-CoV protein. amino acid sequence, structure, self-assembly characteristics, viroporin mechanisms inhibitors are summarized analyzed herein. Although proteins similar respects, specific studies protein, both monomers oligomers, still lacking. A comprehensive understanding should prompt further design characterization effective targeted therapeutic measures.

Language: Английский

Citations

103
Sequences in the cytoplasmic tail of SARS-CoV-2 Spike facilitate expression at the cell surface and syncytia formation DOI Creative Commons
Jérôme Cattin‐Ortolá, Lawrence G. Welch, Sarah Maslen

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Sept. 9, 2021

Abstract The Spike (S) protein of SARS-CoV-2 binds ACE2 to direct fusion with host cells. S comprises a large external domain, transmembrane and short cytoplasmic tail. Understanding the intracellular trafficking is relevant infection, vaccines expressing full-length from mRNA or adenovirus vectors. Here we report proteomic screen for cellular factors that interact tail S. We confirm interactions COPI COPII vesicle coats, ERM family actin regulators, WIPI3 autophagy component. binding site promotes exit endoplasmic reticulum, although should retain in early Golgi where viral budding occurs, there suboptimal histidine residue recognition motif. As result, leaks surface it accumulates can formation multinucleate syncytia. Thus, signals indicate syncytia play role lifecycle.

Language: Английский

Citations

100
Emergence of SARS-CoV-2 Variants in the World: How Could This Happen? DOI Creative Commons
Alfredo Parra-Lucares,

Paula Segura,

Verónica Rojas

et al.

Life, Journal Year: 2022, Volume and Issue: 12(2), P. 194 - 194

Published: Jan. 28, 2022

The COVID-19 pandemic has had a significant global impact, with more than 280,000,000 people infected and 5,400,000 deaths. use of personal protective equipment the anti-SARS-CoV-2 vaccination campaigns have reduced infection death rates worldwide. However, recent increase in been observed associated appearance SARS-CoV-2 variants, including recently described lineage B.1.617.2 (Delta variant) B.1.1.529/BA.1 (Omicron variant). These new variants put effectiveness international at risk, outbreaks throughout world. This emergence due to multiple predisposing factors, molecular characteristics virus, geographic environmental conditions, impact social determinants health that favor genetic diversification SARS-CoV-2. We present literature review on most information available analyzed biological, geographical, sociocultural factors development these variants. Finally, we evaluate surveillance strategies for early detection prevent their distribution outside regions.

Language: Английский

Citations

42
Innate and Adaptive Immunity during SARS-CoV-2 Infection: Biomolecular Cellular Markers and Mechanisms DOI Creative Commons
Brent Brown,

Vanshika Ojha,

Ingo Fricke

et al.

Vaccines, Journal Year: 2023, Volume and Issue: 11(2), P. 408 - 408

Published: Feb. 10, 2023

The coronavirus 2019 (COVID-19) pandemic was caused by a positive sense single-stranded RNA (ssRNA) severe acute respiratory syndrome 2 (SARS-CoV-2). However, other human coronaviruses (hCoVs) exist. Historical pandemics include smallpox and influenza, with efficacious therapeutics utilized to reduce overall disease burden through effectively targeting competent host immune system response. is composed of primary/secondary lymphoid structures initially eight types cell types, many subtypes, traversing membranes utilizing signaling cascades that contribute towards clearance pathogenic proteins. Other proteins discussed cluster differentiation (CD) markers, major histocompatibility complexes (MHC), pleiotropic interleukins (IL), chemokines (CXC). historical concepts immunity are the innate adaptive systems. represented T cells, B antibodies. macrophages, neutrophils, dendritic complement system. viruses can affect regulate cycle progression for example, in cancers papillomavirus (HPV: cervical carcinoma), Epstein-Barr virus (EBV: lymphoma), Hepatitis C (HB/HC: hepatocellular carcinoma) Leukemia Virus-1 (T leukemia). Bacterial infections also increase risk developing cancer (e.g.,

Language: Английский

Citations

39
Spike protein of SARS-CoV-2 variants: a brief review and practical implications DOI Open Access
Kattlyn Laryssa Candido, Caio Ricardo Eich, Luciana Oliveira de Fariña

et al.

Brazilian Journal of Microbiology, Journal Year: 2022, Volume and Issue: 53(3), P. 1133 - 1157

Published: April 9, 2022

Language: Английский

Citations

34
The Envelope (E) Protein of SARS-CoV-2 as a Pharmacological Target DOI Creative Commons
Teresa Santos-Mendoza

Viruses, Journal Year: 2023, Volume and Issue: 15(4), P. 1000 - 1000

Published: April 19, 2023

The COVID-19 pandemic caused by the SARS-CoV-2 virus is still a global health concern. Several spike (S) protein-based vaccines have been developed that efficiently protect human population against severe forms of COVID-19. However, some variants concern (VOCs) emerged evade protective effect vaccine-induced antibodies. Therefore, efficient and specific antiviral treatments to control are indispensable. To date, two drugs approved for mild treatment; nevertheless, more drugs, preferably broad-spectrum ready-to-use therapeutic agents new pandemics, needed. Here, I discuss PDZ-dependent protein-protein interactions viral E protein with host proteins as attractive alternatives development antivirals coronavirus.

Language: Английский

Citations

18
Perturbation of the host cell Ca2+ homeostasis and ER-mitochondria contact sites by the SARS-CoV-2 structural proteins E and M DOI Creative Commons
Elena Poggio, Francesca Vallese, Andreas Hartel

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(4)

Published: April 29, 2023

Abstract Coronavirus disease (COVID-19) is a contagious respiratory caused by the SARS-CoV-2 virus. The clinical phenotypes are variable, ranging from spontaneous recovery to serious illness and death. On March 2020, global COVID-19 pandemic was declared World Health Organization (WHO). As of February 2023, almost 670 million cases 6,8 deaths have been confirmed worldwide. Coronaviruses, including SARS-CoV-2, contain single-stranded RNA genome enclosed in viral capsid consisting four structural proteins: nucleocapsid (N) protein, ribonucleoprotein core, spike (S) envelope (E) membrane (M) embedded surface envelope. In particular, E protein poorly characterized viroporin with high identity amongst all β-coronaviruses (SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-OC43) low mutation rate. Here, we focused our attention on study M proteins, found general perturbation host cell calcium (Ca 2+ ) homeostasis selective rearrangement interorganelle contact sites. vitro vivo biochemical analyses revealed that binding specific nanobodies soluble regions reversed observed phenotypes, suggesting might be an important therapeutic candidate not only for vaccine development, but also management COVID designing drug regimens that, so far, very limited.

Language: Английский

Citations

18