Genetic Conservation and Diversity of SARS‐CoV‐2 Envelope Gene Across Variants of Concern

Journal of Medical Virology, Journal Year: 2025, Volume and Issue: 97(1)

Published: Jan. 1, 2025

ABSTRACT SARS‐CoV‐2 Envelope (E) protein is critical in viral assembly, release, and virulence. E gene was considered highly conserved evolving slowly. Pan‐sarbecoviruses–conserved regions the have been used as targets for various RT‐PCR assays to detect SARS‐CoV‐2. It remains elusive whether variants of concern (VOCs) accumulated significant mutations that may affect stability diagnostic assays. Herein we aimed perform a comprehensive genetic analysis on conservation diversity its VOCs comparison with other human coronaviruses (HCoVs). In silico 20 326 HCoV sequences retrieved from GenBank GISAID suggests has multiple pan‐HCoVs– pan‐SARS‐CoV‐2–conserved positions but accumulates VOC B.1.351 Omicron strains. Mutations were often found 5′ 3′ variable regions, whereas central region conserved. Nucleotide changes C109U A114G lead potential failure first‐line diagnostic/screening change C212U concomitant amino acid substitution Pro71Leu (i.e., C212U/Pro71Leu) hallmark mutation variants, while C26U/Thr9Ile characteristic all variants. Later subvariants, such XBB.1.5 EG.5, additionally acquired A31G/Thr11Ala mutation, confirmed by whole genome sequencing 118 pediatric cases. Wild‐type exhibits cytotoxicity cells, Thr9Ile, Thr11Ala, Thr9Ile + or reduces cytotoxicity. The Thr11Ala stabilizes proteins alters cellular distribution protein, reducing colocalization Golgi body. Altogether, this study not only sheds light also informs improvement development pan‐HCoVs screening

Language: Английский

---

SARS-CoV-2 ORF3a Protein as a Therapeutic Target against COVID-19 and Long-Term Post-Infection Effects

Pathogens, Journal Year: 2024, Volume and Issue: 13(1), P. 75 - 75

Published: Jan. 14, 2024

The COVID-19 pandemic caused by SARS-CoV-2 has posed unparalleled challenges due to its rapid transmission, ability mutate, high mortality and morbidity, enduring health complications. Vaccines have exhibited effectiveness, but their efficacy diminishes over time while new variants continue emerge. Antiviral medications offer a viable alternative, success been inconsistent. Therefore, there remains an ongoing need identify innovative antiviral drugs for treating post-infection ORF3a (open reading frame 3a) protein found in SARS-CoV-2, represents promising target treatment multifaceted role viral pathogenesis, cytokine storms, disease severity, mortality. contributes significantly pathogenesis facilitating assembly release, essential processes the life cycle, also suppressing body’s responses, thus aiding replication. implicated triggering excessive inflammation, characterized NF-κB-mediated production, ultimately leading apoptotic cell death tissue damage lungs, kidneys, central nervous system. Additionally, triggers activation of NLRP3 inflammasome, inciting storm, which is major contributor severity subsequent As with spike protein, undergoes mutations, certain mutant correlate heightened COVID-19. These mutations may influence replication host cellular inflammatory responses. While establishing direct link between difficult, involvement promoting inflammation exacerbating likely higher rates severe cases. This review offers comprehensive detailed exploration ORF3a’s potential as drug target. we outline strategies discovering developing inhibitor counteract harmful effects, alleviate damage, reduce lingering

Language: Английский

---

Insights into the Activation of Unfolded Protein Response Mechanism during Coronavirus Infection

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(5), P. 4286 - 4308

Published: May 5, 2024

Coronaviruses represent a significant class of viruses that affect both animals and humans. Their replication cycle is strongly associated with the endoplasmic reticulum (ER), which, upon virus invasion, triggers ER stress responses. The activation unfolded protein response (UPR) within infected cells performed from three transmembrane receptors, IRE1, PERK, ATF6, results in reduction production, boost ER’s ability to fold proteins properly, initiation ER-associated degradation (ERAD) remove misfolded or proteins. However, cases prolonged severe stress, UPR can also instigate apoptotic cell death inflammation. Herein, we discuss ER-triggered host responses after coronavirus infection, as well pharmaceutical targeting potential antiviral strategy.

Language: Английский

---

SARS-CoV-2-ORF-3a Mediates Apoptosis Through Mitochondrial Dysfunction Modulated by the K+ Ion Channel

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1575 - 1575

Published: Feb. 13, 2025

Coronavirus disease 2019 (COVID-19) causes pulmonary edema, which disrupts the lung alveoli-capillary barrier and leads to cell apoptosis, main cause of death. However, molecular mechanism behind SARS-CoV-2's apoptotic activity remains unknown. Here, we revealed that SARS-CoV-2-ORF-3a mediates pathology associated with SARS-CoV-2, is demonstrated by fact it tissue damage. The in vitro results showed triggers death via disruption mitochondrial homeostasis, modulated through regulation Mitochondrial ATP-sensitive Potassium Channel (MitoKATP). addition exogenous (K+) form potassium chloride (KCl) attenuated apoptosis along inflammatory interferon response (IFN-β) triggered SARS-ORF-3a. K+ strongly suggests dysregulation ion channel function central underlying dysfunction stress induced SARS-CoV-2-ORF-3a. Our designate targeting or its interactions ORF-3a may represent a promising therapeutic strategy mitigate damaging effects infection SARS-CoV-2.

Language: Английский

---

Subcellular localization of SARS-CoV-2 E and 3a proteins along the secretory pathway

Journal of Molecular Histology, Journal Year: 2025, Volume and Issue: 56(2)

Published: March 1, 2025

Abstract SARS-CoV-2 E and 3a proteins are important for the assembly, budding, release of viral particles. These two transmembrane have been implicated in forming channels membrane that allow transport ions to favor replication. During an active infection, both generally localize endoplasmic reticulum (ER), ER-Golgi intermediate compartment (ERGIC), Golgi where assembly occurs. The ER critical proper packaging trafficking cellular along secretory pathways which determine a protein’s final destination inside or outside cell. virus primarily infects epithelial cells highly nature such as those lung gut. Here we quantified distribution human intestinal cell line. We used NaturePatternMatch demonstrate epitope-tagged expressed alone via transient transfection similar immunoreactivity pattern by wild-type infection. While localized with all selected markers varying degrees, protein displayed higher correlation coefficient Golgi, early/late endosome, lysosome, plasma when compared protein. This work is first provide quantification subcellular multiple components pathway serves basis develop models examining how alter proteostasis within these structures affect their function.

Language: Английский

---

A live attenuated SARS-CoV-2 vaccine constructed by dual inactivation of NSP16 and ORF3a

EBioMedicine, Journal Year: 2025, Volume and Issue: 114, P. 105662 - 105662

Published: March 25, 2025

Language: Английский

---

A glimpse into viral warfare: decoding the intriguing role of highly pathogenic coronavirus proteins in apoptosis regulation

Journal of Biomedical Science, Journal Year: 2024, Volume and Issue: 31(1)

Published: July 13, 2024

Coronaviruses employ various strategies for survival, among which the activation of endogenous or exogenous apoptosis stands out, with viral proteins playing a pivotal role. Notably, highly pathogenic coronaviruses such as SARS-CoV-2, SARS-CoV, and MERS-CoV exhibit greater array non-structural compared to low-pathogenic strains, facilitating their ability induce via multiple pathways. Moreover, these are adept at dampening host immune responses, thereby bolstering replication persistence. This review delves into intricate interplay between apoptosis, systematically elucidating molecular mechanisms underpinning induction by proteins. Furthermore, it explores potential therapeutic avenues stemming from inhibition antiviral agents utilization apoptosis-inducing modalities. These insights not only shed light on pathogenesis but also offer novel perspectives cancer therapy.

Language: Английский

---

Effect of Melatonin on Herpesvirus Type 1 Replication

Published: Feb. 29, 2024

Acute HSV-1 infection is associated with mild symptom, such as fever and lesions of the mouth, face skin. This phase followed by a latency period before reactivation which symptoms ranging from ulcers to encephalitis. Despite available anti-HSV-1 drugs, development new antiviral agents sought due presence resistant viruses. Melatonin, molecule secreted pineal gland, has been shown be an antioxidant, inducer antioxidant enzymes, regulator various biological processes. Clinical trials have explored its therapeutic utility in conditions including infections. study focuses on melatonin's role replication underlying mechanisms. Melatonin was found decrease synthesis proteins infected Vero cells measured inmunofluorescence indicating inhibition replication. Additionally, it regulates activities enzymes affects proteasome activity. activates unfolded protein response (UPR) autophagy suppresses apoptosis HSV-1-infected cells. In summary, melatonin demonstrates inhibitory modulating cellular responses, suggesting potential treatment viral

Language: Английский

---

Effect of Melatonin on Herpesvirus Type 1 Replication

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 4037 - 4037

Published: April 4, 2024

Acute HSV-1 infection is associated with mild symptoms, such as fever and lesions of the mouth, face skin. This phase followed by a latency period before reactivation, which symptoms ranging from ulcers to encephalitis. Despite available anti-HSV-1 drugs, development new antiviral agents sought due presence resistant viruses. Melatonin, molecule secreted pineal gland, has been shown be an antioxidant, inducer antioxidant enzymes, regulator various biological processes. Clinical trials have explored its therapeutic utility in conditions including infections. study focuses on melatonin’s role replication underlying mechanisms. Melatonin was found decrease synthesis proteins infected Vero cells measured immunofluorescence, indicating inhibition replication. Additionally, it regulates activities enzymes affects proteasome activity. activates unfolded protein response (UPR) autophagy suppresses apoptosis HSV-1-infected cells. In summary, melatonin demonstrates inhibitory modulating cellular responses, suggesting potential treatment viral

Language: Английский

---

Is Autophagy a Friend or Foe in SARS-CoV-2 Infection?

Viruses, Journal Year: 2024, Volume and Issue: 16(9), P. 1491 - 1491

Published: Sept. 20, 2024

As obligate parasites, viruses need to hijack resources from infected cells complete their lifecycle. The interaction between the virus and host determines viral infection process, including propagation disease’s outcome. Understanding factors is a basis for unraveling intricate biological processes in thereby developing more efficient targeted antivirals. Among various fundamental virus–host interactions, autophagy plays vital also complicated roles by directly engaging lifecycle functioning as an anti- and/or pro-viral factor. Autophagy thus becomes promising target against infection. Since COVID-19 pandemic, there has been accumulation of studies aiming investigate SARS-CoV-2 using different models distinct angles, providing valuable information systematically comprehensively dissecting interplay SARS-CoV-2. In this review, we summarize advancements autophagy, well detailed molecular mechanisms. We update current knowledge on pharmacological strategies used suppress replication through remodeling autophagy. These extensive can advance our understanding virus–autophagy provide insights into antiviral therapeutics regulating

Language: Английский

---