Human Leukocyte Antigen Susceptibility Map for Severe Acute Respiratory Syndrome Coronavirus 2

Journal of Virology, Journal Year: 2020, Volume and Issue: 94(13)

Published: April 20, 2020

Individual genetic variation may help to explain different immune responses a virus across population. In particular, understanding how in HLA affect the course of COVID-19 could identify individuals at higher risk from disease. typing can be fast and inexpensive. Pairing with testing where feasible improve assessment severity viral disease Following development vaccine against SARS-CoV-2, that causes COVID-19, high-risk types prioritized for vaccination.

Language: Английский

---

Bat coronaviruses related to SARS-CoV-2 and infectious for human cells

Nature, Journal Year: 2022, Volume and Issue: 604(7905), P. 330 - 336

Published: Feb. 16, 2022

Language: Английский

---

Applying and improving AlphaFold at CASP14

Proteins Structure Function and Bioinformatics, Journal Year: 2021, Volume and Issue: 89(12), P. 1711 - 1721

Published: Oct. 4, 2021

We describe the operation and improvement of AlphaFold, system that was entered by team AlphaFold2 to "human" category in 14th Critical Assessment Protein Structure Prediction (CASP14). The AlphaFold CASP14 is entirely different one CASP13. It used a novel end-to-end deep neural network trained produce protein structures from amino acid sequence, multiple sequence alignments, homologous proteins. In assessors' ranking summed z scores (>2.0), scored 244.0 compared 90.8 next best group. predictions made had median domain GDT_TS 92.4; this first time level average accuracy has been achieved during CASP, especially on more difficult Free Modeling targets, represents significant state art structure prediction. reported how run as human improved such it now achieves an equivalent performance without intervention, opening door highly accurate large-scale

Language: Английский

---

SARS-CoV-2 Accessory Proteins in Viral Pathogenesis: Knowns and Unknowns

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: July 7, 2021

There are still many unanswered questions concerning viral SARS-CoV-2 pathogenesis in COVID-19. Accessory proteins consist of eleven whose roles during infection not completely understood. Here, a review on the current knowledge accessory is summarized updating new research that could be critical understanding interaction with host. Some such as ORF3b, ORF6, ORF7a and ORF8 have been shown to important IFN-I antagonists inducing an impairment host immune response. In addition, ORF3a involved apoptosis whereas others like ORF9b ORF9c interact cellular organelles leading suppression antiviral response infected cells. However, possible ORF7b ORF10 awaiting described. Also, ORF3d has reassigned. Relevant information knowns unknowns these analyzed, which crucial for further design strategies counteracting their actions evading responses

Language: Английский

---

Structure of SARS-CoV-2 ORF8, a rapidly evolving immune evasion protein

Proceedings of the National Academy of Sciences, Journal Year: 2020, Volume and Issue: 118(2)

Published: Dec. 23, 2020

Significance The structure of the SARS-CoV-2 ORF8 protein reveals two novel intermolecular interfaces layered onto an ORF7 fold. One is mediated by a disulfide bond, other noncovalent, and both are with respect to SARS-CoV. structural analysis here establishes molecular framework for understanding rapid evolution ORF8, its contributions COVID-19 pathogenesis, potential neutralization antibodies.

Language: Английский

---

Structural Characterization of SARS-CoV-2: Where We Are, and Where We Need to Be

Frontiers in Molecular Biosciences, Journal Year: 2020, Volume and Issue: 7

Published: Dec. 17, 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread in humans almost every country, causing the disease COVID-19. Since start of COVID-19 pandemic, research efforts have been strongly directed towards obtaining a full understanding biology viral infection, order to develop vaccine and therapeutic approaches. In particular, structural studies allowed comprehend molecular basis underlying role many SARS-CoV-2 proteins, make rapid progress treatment preventive therapeutics. Despite great advances that provided by these studies, knowledge gaps on infection still remain. Filling will be key tackle this through development effective treatments specific vaccination strategies.

Language: Английский

---

Lost in deletion: The enigmatic ORF8 protein of SARS-CoV-2

Biochemical and Biophysical Research Communications, Journal Year: 2020, Volume and Issue: 538, P. 116 - 124

Published: Oct. 21, 2020

Language: Английский

---

Structural insight reveals SARS-CoV-2 ORF7a as an immunomodulating factor for human CD14+ monocytes

iScience, Journal Year: 2021, Volume and Issue: 24(3), P. 102187 - 102187

Published: Feb. 16, 2021

Dysregulated immune cell responses have been linked to the severity of coronavirus disease 2019 (COVID-19), but specific viral factors severe acute respiratory syndrome 2 (SARS-CoV-2) were currently unknown. Herein, we reveal that Immunoglobulin-like fold ectodomain protein SARS-CoV-2 ORF7a interacts with high efficiency CD14+ monocytes in human peripheral blood, compared pathogenic SARS-CoV ORF7a. The crystal structure at 2.2 Å resolution reveals three remarkable changes on amphipathic side four-stranded β-sheet, implying a potential functional interface protein. Importantly, coincubation ex vivo triggered decrease HLA-DR/DP/DQ expression levels and upregulated significant production proinflammatory cytokines, including IL-6, IL-1β, IL-8, TNF-α. Our work demonstrates is an immunomodulating factor for binding triggers dramatic inflammatory responses, providing promising therapeutic drug targets pandemic COVID-19.

Language: Английский

---

Structural and non-structural proteins in SARS-CoV-2: potential aspects to COVID-19 treatment or prevention of progression of related diseases

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: May 15, 2023

Coronavirus disease 2019 (COVID-19) is caused by a new member of the Coronaviridae family known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are structural and non-structural proteins (NSPs) in genome this virus. S, M, H, E proteins, NSPs include accessory replicase proteins. The NSP components SARS-CoV-2 play an important role its infectivity, some them may be pathogenesis chronic diseases, including cancer, coagulation disorders, neurodegenerative cardiovascular diseases. interact with targets such angiotensin-converting enzyme (ACE2) receptor. In addition, can stimulate pathological intracellular signaling pathways triggering transcription factor hypoxia-inducible factor-1 (HIF-1), neuropilin-1 (NRP-1), CD147, Eph receptors, which roles progression diseases like Alzheimer's disease, epilepsy, multiple sclerosis, cancers glioblastoma, lung malignancies, leukemias. Several compounds polyphenols, doxazosin, baricitinib, ruxolitinib could inhibit these interactions. It has been demonstrated that spike protein stronger affinity for human ACE2 than SARS-CoV, leading current study to hypothesize newly produced variant Omicron receptor-binding domain (RBD) binds more strongly primary strain. SARS Middle East (MERS) viruses against have become resistant previous vaccines. Therefore, review recent studies performance vaccines their effects on COVID-19 related vital need deal conditions. This examines potential initiation it anticipated serve effective vaccine or treatment Video Abstract.

Language: Английский

---

Infection of human Nasal Epithelial Cells with SARS-CoV-2 and a 382-nt deletion isolate lacking ORF8 reveals similar viral kinetics and host transcriptional profiles

PLoS Pathogens, Journal Year: 2020, Volume and Issue: 16(12), P. e1009130 - e1009130

Published: Dec. 7, 2020

The novel coronavirus SARS-CoV-2 is the causative agent of Coronavirus Disease 2019 (COVID-19), a global healthcare and economic catastrophe. Understanding host immune response to still in its infancy. A 382-nt deletion strain lacking ORF8 (Δ382 herein) was isolated Singapore March 2020. Infection with Δ382 associated less severe disease patients, compared infection wild-type SARS-CoV-2. Here, we established Nasal Epithelial cells (NECs) differentiated from healthy nasal-tissue derived stem as suitable model for ex-vivo study mediated pathogenesis. NECs either or resulted virus particles released exclusively apical side, similar replication kinetics. Screening panel 49 cytokines basolateral secretion infected identified CXCL10 only cytokine significantly induced upon infection, at comparable levels both cells. Transcriptome analysis revealed temporal up-regulation distinct gene subsets during anti-viral signaling pathways detected late time-points (72 hours post-infection, hpi). This attenuated when an influenza strain, H3N2, which elicited inflammatory within 8 hpi, greater magnitude time-points. Remarkably, transcriptional nearly identical that every post-infection time-point examined. In accordance previous results, showed absence transcripts mapping ORF8, conserved expression other genes. Our findings shed light on airway epithelial demonstrate non-essential role modulating production

Language: Английский

---