scholarly journals The SARS-Coronavirus Infection Cycle: A Survey of Viral Membrane Proteins, Their Functional Interactions and Pathogenesis

2021 ◽  
Vol 22 (3) ◽  
pp. 1308 ◽  
Author(s):  
Nicholas A. Wong ◽  
Milton H. Saier
Keyword(s):  
Membrane Proteins ◽  
Vaccine Development ◽  
Severe Disease ◽  
Transmembrane Proteins ◽  
Infection Process ◽  
Cellular Growth ◽  
Infection Cycle ◽  
Health Crisis ◽  
Attenuated Viruses ◽  
And Function

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a novel epidemic strain of Betacoronavirus that is responsible for the current viral pandemic, coronavirus disease 2019 (COVID-19), a global health crisis. Other epidemic Betacoronaviruses include the 2003 SARS-CoV-1 and the 2009 Middle East Respiratory Syndrome Coronavirus (MERS-CoV), the genomes of which, particularly that of SARS-CoV-1, are similar to that of the 2019 SARS-CoV-2. In this extensive review, we document the most recent information on Coronavirus proteins, with emphasis on the membrane proteins in the Coronaviridae family. We include information on their structures, functions, and participation in pathogenesis. While the shared proteins among the different coronaviruses may vary in structure and function, they all seem to be multifunctional, a common theme interconnecting these viruses. Many transmembrane proteins encoded within the SARS-CoV-2 genome play important roles in the infection cycle while others have functions yet to be understood. We compare the various structural and nonstructural proteins within the Coronaviridae family to elucidate potential overlaps and parallels in function, focusing primarily on the transmembrane proteins and their influences on host membrane arrangements, secretory pathways, cellular growth inhibition, cell death and immune responses during the viral replication cycle. We also offer bioinformatic analyses of potential viroporin activities of the membrane proteins and their sequence similarities to the Envelope (E) protein. In the last major part of the review, we discuss complement, stimulation of inflammation, and immune evasion/suppression that leads to CoV-derived severe disease and mortality. The overall pathogenesis and disease progression of CoVs is put into perspective by indicating several stages in the resulting infection process in which both host and antiviral therapies could be targeted to block the viral cycle. Lastly, we discuss the development of adaptive immunity against various structural proteins, indicating specific vulnerable regions in the proteins. We discuss current CoV vaccine development approaches with purified proteins, attenuated viruses and DNA vaccines.

How Do Lipids Affect the Structure and Function of Integral Membrane Proteins

2012 ◽  
Vol 28 (11) ◽  
pp. 866
Author(s):  
Jie HENG ◽  
Yan WU ◽  
Xianping WANG ◽  
Kai ZHANG
Keyword(s):  
Membrane Proteins ◽  
Structure And Function ◽  
Integral Membrane Proteins ◽  
And Function

Molecular characterization of SARS-CoV-2

2020 ◽  
Vol 20 ◽  
Author(s):  
Miribane Dërmaku-Sopjani ◽  
Mentor Sopjani
Keyword(s):  
Public Health ◽  
Drug Targets ◽  
Virus Genome ◽  
Health Crisis ◽  
Public Health Crisis ◽  
Therapeutic Drugs ◽  
New Public Health ◽  
New Public ◽  
And Function

Abstract:: The coronavirus disease 2019 (COVID-19) is currently a new public health crisis threatening the world. This pandemic disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus has been reported to be originated in bats and by yet unknown intermediary animals were transmitted to humans in China 2019. The SARSCoV- 2 spreads faster than its two ancestors the SARS-CoV and Middle East respiratory syndrome coronavirus (MERSCoV) but has reduced fatality. At present, the SARS-CoV-2 has caused about a 1.16 million of deaths with more than 43.4 million confirmed cases worldwide, resulting in a serious threat to public health globally with yet uncertain impact. The disease is transmitted by inhalation or direct contact with an infected person. The incubation period ranges from 1 to 14 days. COVID-19 is accompanied by various symptoms, including cough, fatigue. In most people the disease is mild, but in some other people, such as in elderly and people with chronic diseases, it may progress from pneumonia to a multi-organ dysfunction. Many people are reported asymptomatic. The virus genome is sequenced, but new variants are reported. Numerous biochemical aspects of its structure and function are revealed. To date, no clinically approved vaccines and/or specific therapeutic drugs are available to prevent or treat the COVID-19. However, there are reported intensive researches on the SARSCoV- 2 to potentially identify vaccines and/or drug targets, which may help to overcome the disease. In this review, we discuss recent advances in understanding the molecular structure of SARS-CoV-2 and its biochemical characteristics.

scholarly journals COVID-19 in obstetrics 2020: the experience at a New York City medical center

2020 ◽  
Vol 48 (9) ◽  
pp. 892-899
Author(s):  
Ashlesha K. Dayal ◽  
Armin S. Razavi ◽  
Amir K. Jaffer ◽  
Nishant Prasad ◽  
Daniel W. Skupski
Keyword(s):  
New York ◽  
Medical Center ◽  
Severe Disease ◽  
Infection Rates ◽  
Health Crisis ◽  
The Public ◽  
Public Health Crisis ◽  
Asymptomatic Carriage ◽  
Global Spread ◽  
Workforce Flexibility

AbstractThe global spread of the SARS-CoV-2 virus during the early months of 2020 was rapid and exposed vulnerabilities in health systems throughout the world. Obstetric SARS-CoV-2 disease was discovered to be largely asymptomatic carriage but included a small rate of severe disease with rapid decompensation in otherwise healthy women. Higher rates of hospitalization, Intensive Care Unit (ICU) admission and intubation, along with higher infection rates in minority and disadvantaged populations have been documented across regions. The operational gymnastics that occurred daily during the Covid-19 emergency needed to be translated to the obstetrics realm, both inpatient and ambulatory. Resources for adaptation to the public health crisis included workforce flexibility, frequent communication of operational and protocol changes for evaluation and management, and application of innovative ideas to meet the demand.

scholarly journals Commuting to Work: Nucleolar Long Non-Coding RNA Control Ribosome Biogenesis from Near and Far

2021 ◽  
Vol 7 (3) ◽  
pp. 42
Author(s):  
Victoria Mamontova ◽  
Barbara Trifault ◽  
Lea Boten ◽  
Kaspar Burger
Keyword(s):  
Gene Expression ◽  
Rna Polymerase Ii ◽  
Ribosome Biogenesis ◽  
Intergenic Spacer ◽  
Cellular Growth ◽  
Rrna Synthesis ◽  
Protein Coding ◽  
Non Coding Rna ◽  
And Function ◽  
In Cis

Gene expression is an essential process for cellular growth, proliferation, and differentiation. The transcription of protein-coding genes and non-coding loci depends on RNA polymerases. Interestingly, numerous loci encode long non-coding (lnc)RNA transcripts that are transcribed by RNA polymerase II (RNAPII) and fine-tune the RNA metabolism. The nucleolus is a prime example of how different lncRNA species concomitantly regulate gene expression by facilitating the production and processing of ribosomal (r)RNA for ribosome biogenesis. Here, we summarise the current findings on how RNAPII influences nucleolar structure and function. We describe how RNAPII-dependent lncRNA can both promote nucleolar integrity and inhibit ribosomal (r)RNA synthesis by modulating the availability of rRNA synthesis factors in trans. Surprisingly, some lncRNA transcripts can directly originate from nucleolar loci and function in cis. The nucleolar intergenic spacer (IGS), for example, encodes nucleolar transcripts that counteract spurious rRNA synthesis in unperturbed cells. In response to DNA damage, RNAPII-dependent lncRNA originates directly at broken ribosomal (r)DNA loci and is processed into small ncRNA, possibly to modulate DNA repair. Thus, lncRNA-mediated regulation of nucleolar biology occurs by several modes of action and is more direct than anticipated, pointing to an intimate crosstalk of RNA metabolic events.

scholarly journals Pathophysiology of acute respiratory syndrome coronavirus 2 infection: a systematic literature review to inform EULAR points to consider

RMD Open ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. e001549 ◽  
Author(s):  
Aurélie Najm ◽  
Alessia Alunno ◽  
Xavier Mariette ◽  
Benjamin Terrier ◽  
Gabriele De Marco ◽  
...  
Keyword(s):  
Literature Review ◽  
Systematic Literature Review ◽  
Immune Cell ◽  
Severe Disease ◽  
Cell Phenotype ◽  
Loss Of Function ◽  
Humoral And Cellular Immunity ◽  
Host Immune Responses ◽  
Disease Spectrum ◽  
And Function

BackgroundThe SARS-CoV-2 pandemic is a global health problem. Beside the specific pathogenic effect of SARS-CoV-2, incompletely understood deleterious and aberrant host immune responses play critical roles in severe disease. Our objective was to summarise the available information on the pathophysiology of COVID-19.MethodsTwo reviewers independently identified eligible studies according to the following PICO framework: P (population): patients with SARS-CoV-2 infection; I (intervention): any intervention/no intervention; C (comparator): any comparator; O (outcome) any clinical or serological outcome including but not limited to immune cell phenotype and function and serum cytokine concentration.ResultsOf the 55 496 records yielded, 84 articles were eligible for inclusion according to question-specific research criteria. Proinflammatory cytokine expression, including interleukin-6 (IL-6), was increased, especially in severe COVID-19, although not as high as other states with severe systemic inflammation. The myeloid and lymphoid compartments were differentially affected by SARS-CoV-2 infection depending on disease phenotype. Failure to maintain high interferon (IFN) levels was characteristic of severe forms of COVID-19 and could be related to loss-of-function mutations in the IFN pathway and/or the presence of anti-IFN antibodies. Antibody response to SARS-CoV-2 infection showed a high variability across individuals and disease spectrum. Multiparametric algorithms showed variable diagnostic performances in predicting survival, hospitalisation, disease progression or severity, and mortality.ConclusionsSARS-CoV-2 infection affects both humoral and cellular immunity depending on both disease severity and individual parameters. This systematic literature review informed the EULAR ‘points to consider’ on COVID-19 pathophysiology and immunomodulatory therapies.

Nanoscale lipid membrane mimetics in spin-labeling and electron paramagnetic resonance spectroscopy studies of protein structure and function

2017 ◽  
Vol 6 (1) ◽  
pp. 75-92 ◽  
Author(s):  
Elka R. Georgieva
Keyword(s):  
Electron Paramagnetic Resonance ◽  
Protein Structure ◽  
Membrane Proteins ◽  
Membrane Protein ◽  
Spin Labeling ◽  
Structure And Function ◽  
Protein Structure And Function ◽  
Paramagnetic Resonance ◽  
And Function ◽  
Electron Paramagnetic

AbstractCellular membranes and associated proteins play critical physiological roles in organisms from all life kingdoms. In many cases, malfunction of biological membranes triggered by changes in the lipid bilayer properties or membrane protein functional abnormalities lead to severe diseases. To understand in detail the processes that govern the life of cells and to control diseases, one of the major tasks in biological sciences is to learn how the membrane proteins function. To do so, a variety of biochemical and biophysical approaches have been used in molecular studies of membrane protein structure and function on the nanoscale. This review focuses on electron paramagnetic resonance with site-directed nitroxide spin-labeling (SDSL EPR), which is a rapidly expanding and powerful technique reporting on the local protein/spin-label dynamics and on large functionally important structural rearrangements. On the other hand, adequate to nanoscale study membrane mimetics have been developed and used in conjunction with SDSL EPR. Primarily, these mimetics include various liposomes, bicelles, and nanodiscs. This review provides a basic description of the EPR methods, continuous-wave and pulse, applied to spin-labeled proteins, and highlights several representative applications of EPR to liposome-, bicelle-, or nanodisc-reconstituted membrane proteins.

scholarly journals Coronaviruses as Vectors: Stability of Foreign Gene Expression

2005 ◽  
Vol 79 (20) ◽  
pp. 12742-12751 ◽  
Author(s):  
Cornelis A. M. de Haan ◽  
Bert Jan Haijema ◽  
David Boss ◽  
Frank W. H. Heuts ◽  
Peter J. M. Rottier
Keyword(s):  
Genetic Stability ◽  
Vaccine Development ◽  
Hepatitis Virus ◽  
Firefly Luciferase ◽  
Foreign Gene ◽  
Rna Recombination ◽  
Large Deletions ◽  
Group 2 ◽  
Attenuated Viruses ◽  
Foreign Genes

ABSTRACT Coronaviruses are enveloped, positive-stranded RNA viruses considered to be promising vectors for vaccine development, as (i) genes can be deleted, resulting in attenuated viruses; (ii) their tropism can be modified by manipulation of their spike protein; and (iii) heterologous genes can be expressed by simply inserting them with appropriate coronaviral transcription signals into the genome. For any live vector, genetic stability is an essential requirement. However, little is known about the genetic stability of recombinant coronaviruses expressing foreign genes. In this study, the Renilla and the firefly luciferase genes were systematically analyzed for their stability after insertion at various genomic positions in the group 1 coronavirus feline infectious peritonitis virus and in the group 2 coronavirus mouse hepatitis virus. It appeared that the two genes exhibit intrinsic differences, the Renilla gene consistently being maintained more stably than the firefly gene. This difference was not caused by genome size restrictions, by different effects of the encoded proteins, or by different consequences of the synthesis of the additional subgenomic mRNAs. The loss of expression of the firefly luciferase was found to result from various, often large deletions of the gene, probably due to RNA recombination. The extent of this process appeared to depend strongly on the coronaviral genomic background, the luciferase gene being much more stable in the feline than in the mouse coronavirus genome. It also depended significantly on the particular genomic location at which the gene was inserted. The data indicate that foreign sequences are more stably maintained when replacing nonessential coronaviral genes.

scholarly journals The Relationship between Structural Symmetry and Function in Membrane Proteins

2021 ◽  
Vol 120 (3) ◽  
pp. 24a-25a
Author(s):  
Emily L. Yaklich ◽  
Antoniya A. Aleksandrova ◽  
Lucy R. Forrest
Keyword(s):  
Membrane Proteins ◽  
Structural Symmetry ◽  
And Function ◽  
The Relationship
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