scholarly journals Structure and Function of Major SARS-CoV-2 and SARS-CoV Proteins

2021 ◽  
Vol 15 ◽  
pp. 117793222110258
Author(s):  
Ritesh Gorkhali ◽  
Prashanna Koirala ◽  
Sadikshya Rijal ◽  
Ashmita Mainali ◽  
Adesh Baral ◽  
...  
Keyword(s):  
Genomic Organization ◽  
Membrane Vesicles ◽  
Structural Proteins ◽  
Host Immune System ◽  
Accessory Proteins ◽  
Nonstructural Proteins ◽  
N Protein ◽  
Small Proteins ◽  
Methylation Mark ◽  
And Function

SARS-CoV-2 virus, the causative agent of COVID-19 pandemic, has a genomic organization consisting of 16 nonstructural proteins (nsps), 4 structural proteins, and 9 accessory proteins. Relative of SARS-CoV-2, SARS-CoV, has genomic organization, which is very similar. In this article, the function and structure of the proteins of SARS-CoV-2 and SARS-CoV are described in great detail. The nsps are expressed as a single or two polyproteins, which are then cleaved into individual proteins using two proteases of the virus, a chymotrypsin-like protease and a papain-like protease. The released proteins serve as centers of virus replication and transcription. Some of these nsps modulate the host’s translation and immune systems, while others help the virus evade the host immune system. Some of the nsps help form replication-transcription complex at double-membrane vesicles. Others, including one RNA-dependent RNA polymerase and one exonuclease, help in the polymerization of newly synthesized RNA of the virus and help minimize the mutation rate by proofreading. After synthesis of the viral RNA, it gets capped. The capping consists of adding GMP and a methylation mark, called cap 0 and additionally adding a methyl group to the terminal ribose called cap1. Capping is accomplished with the help of a helicase, which also helps remove a phosphate, two methyltransferases, and a scaffolding factor. Among the structural proteins, S protein forms the receptor of the virus, which latches on the angiotensin-converting enzyme 2 receptor of the host and N protein binds and protects the genomic RNA of the virus. The accessory proteins found in these viruses are small proteins with immune modulatory roles. Besides functions of these proteins, solved X-ray and cryogenic electron microscopy structures related to the function of the proteins along with comparisons to other coronavirus homologs have been described in the article. Finally, the rate of mutation of SARS-CoV-2 residues of the proteome during the 2020 pandemic has been described. Some proteins are mutated more often than other proteins, but the significance of these mutation rates is not fully understood.

SARS-CoV-2 proteins: Are they useful as targets for COVID-19 drugs and vaccines?

2021 ◽  
Vol 21 ◽  
Author(s):  
Mohammed Elimam Ahamed Mohammed
Keyword(s):  
Lipid Bilayer ◽  
Drug Targets ◽  
Protein S ◽  
Bilayer Membrane ◽  
Viral Envelope ◽  
Host Cells ◽  
Spike Protein ◽  
Structural Proteins ◽  
Accessory Proteins ◽  
N Protein

: The proteins of coronavirus are classified to nonstructural, structural, and accessory. There are 16 nonstructural viral proteins beside their precursors (1a and 1ab polyproteins). The nonstructural proteins are named as nsp1 to nsp16 and they act as enzymes, coenzymes, and binding proteins to facilitate the replication, transcription, and translation of the virus. The structural proteins are bound to the RNA in the nucleocapsid (N- protein) or to the lipid bilayer membrane of the viral envelope. The lipid bilayer proteins include the membrane protein (M), envelope protein (E), and spike protein (S). Beside their role as structural proteins, they are essential for the host cells binding and invasion. The SARS-CoV-2 contains six accessory proteins which participates in the viral replication, assembly and virus- host interactions. The SARS-CoV-2 accessory proteins are orf3a, orf6, orf7a, orf7b, orf8, and orf10. The functions of the SARS-CoV-2 are not well known, while the functions of their corresponding proteins in SARS-CoV are either well known or poorly studied. Recently, the Oxford University and Pfizer and BioNTech made SARS-CoV-2 vaccines through targeting the spike protein gene. The US Food and Drug Administration (FDA) and the health authorities of the United Kingdom approved and started vaccination using the Pfizer and BioNTech mRNA vaccine. Also, The FDA of USA approved the treatment of COVID-19 using two monoclonal antibodies produced by Regeneron pharmaceuticals to target the spike protein. The SARS-CoV-2 proteins can be used for the diagnosis, as drug targets and in vaccination trials for COVID-19. For future COVID-19 research, more efforts should be done to elaborate the functions and structure of the SARS-CoV-2 proteins so as to use them as targets for COVID-19 drug and vaccines. Special attention should be drawn to extensive research on the SARS-CoV-2 nsp3, orf8, and orf10.

scholarly journals Antibody landscape against SARS-CoV-2 proteome revealed significant differences between non-structural/ accessory proteins and structural proteins

2020 ◽  
Author(s):  
Yang Li ◽  
Zhaowei Xu ◽  
Qing Lei ◽  
Dan-yun Lai ◽  
Hongyan Hou ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Antibody Response ◽  
Disease Severity ◽  
Sharp Decrease ◽  
Antibody Responses ◽  
Structural Proteins ◽  
List Type ◽  
Accessory Proteins ◽  
Igg Antibodies ◽  
N Protein

SummaryThe immunogenicity of SARS-CoV-2 proteome is largely unknown, especially for non-structural proteins and accessory proteins. Here we collected 2,360 COVID-19 sera and 601 control sera. We analyzed these sera on a protein microarray with 20 proteins of SARS-CoV-2, built an antibody response landscape for IgG and IgM. We found that non-structural proteins and accessory proteins NSP1, NSP7, NSP8, RdRp, ORF3b and ORF9b elicit prevalent IgG responses. The IgG patterns and dynamic of non-structural/ accessory proteins are different from that of S and N protein. The IgG responses against these 6 proteins are associated with disease severity and clinical outcome and declined sharply about 20 days after symptom onset. In non-survivors, sharp decrease of IgG antibodies against S1 and N protein before death was observed. The global antibody responses to non-structural/ accessory proteins revealed here may facilitate deeper understanding of SARS-CoV-2 immunology.HighlightsAn antibody response landscape against SARS-CoV-2 proteome was constructedNon-structural/accessory proteins elicit prevalent antibody responses but likely through a different mechanism to that of structural proteinsIgG antibodies against non-structural/accessory proteins are more associated with disease severity and clinical outcomeFor non-survivors, the levels of IgG antibodies against S1 and N decline significantly before death

scholarly journals The Genomic and Structural Organization of SARS-CoV-2: A Mutational Perspective

2021 ◽  
Vol 3 (1) ◽  
pp. 59-65
Author(s):  
Mohammad K. Parvez ◽  
Sakina Niyazi
Keyword(s):  
Cell Attachment ◽  
Proteolytic Processing ◽  
Open Reading Frames ◽  
Structural Proteins ◽  
Accessory Proteins ◽  
The Novel ◽  
Virion Assembly ◽  
The United Kingdom ◽  
Small Proteins ◽  
Recent Emergence

The ongoing pandemic due to the novel SARS-CoV-2 disease (COVID-19) has exerted a great toll on human health. The SARS-CoV-2 is the third most pathogenic human CoV after SARS-CoV-1 and MERS-CoV, which is classified within the genus Betacoronavirus. Though the actual source of its origin and transmission is still unclear, genetic analysis has shown its very close similarity (~96%) with bat SARS-like CoV. SARS-CoV-2 is a spherically-icosahedral virus with a plus-sense single-strand RNA (~30 kb) genome defined into thirteen open reading frames, which encode 2 non-structural polyproteins, 4 structural proteins and 6 accessory proteins. Of its structural proteins the ‘S1’ subunit of spike (S) contains the cellular ACE-2 receptor binding domain (RBD) whereas the ‘S2’ subunit is required for cell membrane fusion. The membrane (M) protein participates in cell-fusion whereas envelope (E) is necessary for virion assembly and morphogenesis. The non-structural polyproteins (pp1a and pp1b) undergo proteolytic processing to produce a total of 16 small proteins, which are involved in mRNA synthesis and replication. Of the accessory proteins (3a, 6, 7a, 7b, 8 and 9b), few are known to modulate host-innate immunity. Interestingly, ‘3b’ is absent in SARS-CoV-2 that significantly differentiates it from other human CoV. Detection of several novel mutations in ‘3a’, ‘3b’ and ‘ORF8’ proteins, notably in the ‘S’ RBD strongly suggest SARS-CoV-2 enhanced cell attachment and facilitated entry, its high infectivity and disease severity in humans. The recent emergence of highly contagious SARS-CoV-2 RBD variants in the United Kingdom (B.1.1.7 strain), South Africa (B.1.351 strain) and Brazil (P.1 strain), and their subsequent spread to other counties have raised serious concerns. Doi: 10.28991/SciMedJ-2021-0301-8 Full Text: PDF

scholarly journals Insight into the emerging role of SARS-CoV-2 nonstructural and accessory proteins in modulation of multiple mechanisms of host innate defense

2021 ◽  
Author(s):  
Abualgasim Elgaili Abdalla ◽  
Jianping Xie ◽  
Kashaf Junaid ◽  
Sonia Younas ◽  
Tilal Elsaman ◽  
...  
Keyword(s):  
Immune Evasion ◽  
Open Reading Frames ◽  
Health Concern ◽  
Host Immune System ◽  
Type I ◽  
Accessory Proteins ◽  
Nonstructural Proteins ◽  
Innate Defense ◽  
Current Review ◽  
Pathway Activation

Coronavirus disease-19 (COVID-19) is an extremely infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has become a major global health concern. The induction of a coordinated immune response is crucial to the elimination of any pathogenic infection. However, SARS-CoV-2 can modulate the host immune system to favor viral adaptation and persistence within the host. The virus can counteract type I interferon (IFN-I) production, attenuating IFN-I signaling pathway activation and disrupting antigen presentation. Simultaneously, SARS-CoV-2 infection can enhance apoptosis and the production of inflammatory mediators, which ultimately results in increased disease severity. SARS-CoV-2 produces an array of effector molecules, including nonstructural proteins (NSPs) and open-reading frames (ORFs) accessory proteins. We describe the complex molecular interplay of SARS-CoV-2 NSPs and accessory proteins with the host’s signaling mediating immune evasion in the current review. In addition, the crucial role played by immunomodulation therapy to address immune evasion is discussed. Thus, the current review can provide new directions for the development of vaccines and specific therapies.

scholarly journals Membrane Vesicle Release in Bacteria, Eukaryotes, and Archaea: a Conserved yet Underappreciated Aspect of Microbial Life

2012 ◽  
Vol 80 (6) ◽  
pp. 1948-1957 ◽  
Author(s):  
Brooke L. Deatherage ◽  
Brad T. Cookson
Keyword(s):  
Membrane Vesicle ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Host Immune System ◽  
Vesicle Release ◽  
Communication Signals ◽  
Microbial Life ◽  
Functional Features

ABSTRACTInteraction of microbes with their environment depends on features of the dynamic microbial surface throughout cell growth and division. Surface modifications, whether used to acquire nutrients, defend against other microbes, or resist the pressures of a host immune system, facilitate adaptation to unique surroundings. The release of bioactive membrane vesicles (MVs) from the cell surface is conserved across microbial life, in bacteria, archaea, fungi, and parasites. MV production occurs not onlyin vitrobut alsoin vivoduring infection, underscoring the influence of these surface organelles in microbial physiology and pathogenesis through delivery of enzymes, toxins, communication signals, and antigens recognized by the innate and adaptive immune systems. Derived from a variety of organisms that span kingdoms of life and called by several names (membrane vesicles, outer membrane vesicles [OMVs], exosomes, shedding microvesicles, etc.), the conserved functions and mechanistic strategies of MV release are similar, including the use of ESCRT proteins and ESCRT protein homologues to facilitate these processes in archaea and eukaryotic microbes. Although forms of MV release by different organisms share similar visual, mechanistic, and functional features, there has been little comparison across microbial life. This underappreciated conservation of vesicle release, and the resulting functional impact throughout the tree of life, explored in this review, stresses the importance of vesicle-mediated processes throughout biology.

scholarly journals The Microbiotic Highway to Health—New Perspective on Food Structure, Gut Microbiota, and Host Inflammation

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1590 ◽  
Author(s):  
Nina Hansen ◽  
Anette Sams
Keyword(s):  
Immune System ◽  
Gut Microbiota ◽  
Dietary Habits ◽  
Gut Hormones ◽  
Host Immune System ◽  
Inflammatory Conditions ◽  
Food Structure ◽  
New Perspective ◽  
And Function ◽  
The Impact

This review provides evidence that not only the content of nutrients but indeed the structural organization of nutrients is a major determinant of human health. The gut microbiota provides nutrients for the host by digesting food structures otherwise indigestible by human enzymes, thereby simultaneously harvesting energy and delivering nutrients and metabolites for the nutritional and biological benefit of the host. Microbiota-derived nutrients, metabolites, and antigens promote the development and function of the host immune system both directly by activating cells of the adaptive and innate immune system and indirectly by sustaining release of monosaccharides, stimulating intestinal receptors and secreting gut hormones. Multiple indirect microbiota-dependent biological responses contribute to glucose homeostasis, which prevents hyperglycemia-induced inflammatory conditions. The composition and function of the gut microbiota vary between individuals and whereas dietary habits influence the gut microbiota, the gut microbiota influences both the nutritional and biological homeostasis of the host. A healthy gut microbiota requires the presence of beneficial microbiotic species as well as vital food structures to ensure appropriate feeding of the microbiota. This review focuses on the impact of plant-based food structures, the “fiber-encapsulated nutrient formulation”, and on the direct and indirect mechanisms by which the gut microbiota participate in host immune function.

Comparative analysis of the ontogeny of a sodium-dependent bile acid transporter in rat kidney and ileum

1996 ◽  
Vol 271 (2) ◽  
pp. G377-G385 ◽  
Author(s):  
D. M. Christie ◽  
P. A. Dawson ◽  
S. Thevananther ◽  
B. L. Shneider
Keyword(s):  
Bile Acid ◽  
Rat Kidney ◽  
Membrane Vesicles ◽  
Mrna Levels ◽  
Sodium Dependent ◽  
Bile Acid Transporter ◽  
Old Rats ◽  
Acid Transporter ◽  
The Difference ◽  
And Function

An apical sodium-dependent bile acid transporter (ASBT) has recently been cloned and characterized in the rat ileum. Northern and Western blotting revealed both the ASBT mRNA and protein in rat kidney. The coding sequence of the kidney transcript was found to be identical to the previously cloned ileal ASBT. Indirect immunofluorescence studies localized the ASBT protein to the apical membrane of the renal proximal convoluted tubule. Kinetic analysis of sodium-dependent taurocholate uptake using membrane vesicles revealed a similar Michaelis-Menten constant value for taurocholate in the kidney and intestine. ASBT protein and function were present in the kidney but not the ileum from 7-day-old rats. On postnatal day 7, there was a sevenfold increase in ASBT steady-state mRNA levels in the kidney relative to the ileum, yet nuclear run-on assays revealed that the nascent transcription rates at this age were virtually the same. This suggests that the difference in the neonatal expression of the ASBT gene in the kidney and ileum may be in part due to differences in mRNA stability.

scholarly journals The mitochondrial ADP/ATP carrier exists and functions as a monomer

2020 ◽  
Vol 48 (4) ◽  
pp. 1419-1432 ◽  
Author(s):  
Edmund R.S. Kunji ◽  
Jonathan J. Ruprecht
Keyword(s):  
Conformational Changes ◽  
Membrane Vesicles ◽  
Native Mass Spectrometry ◽  
Published Data ◽  
Oligomeric State ◽  
Technical Errors ◽  
Density Maps ◽  
Mitochondrial Carrier Family ◽  
The Difference ◽  
And Function

For more than 40 years, the oligomeric state of members of the mitochondrial carrier family (SLC25) has been the subject of debate. Initially, the consensus was that they were dimeric, based on the application of a large number of different techniques. However, the structures of the mitochondrial ADP/ATP carrier, a member of the family, clearly demonstrated that its structural fold is monomeric, lacking a conserved dimerisation interface. A re-evaluation of previously published data, with the advantage of hindsight, concluded that technical errors were at the basis of the earlier dimer claims. Here, we revisit this topic, as new claims for the existence of dimers of the bovine ADP/ATP carrier have emerged using native mass spectrometry of mitochondrial membrane vesicles. However, the measured mass does not agree with previously published values, and a large number of post-translational modifications are proposed to account for the difference. Contrarily, these modifications are not observed in electron density maps of the bovine carrier. If they were present, they would interfere with the structure and function of the carrier, including inhibitor and substrate binding. Furthermore, the reported mass does not account for three tightly bound cardiolipin molecules, which are consistently observed in other studies and are important stabilising factors for the transport mechanism. The monomeric carrier has all of the required properties for a functional transporter and undergoes large conformational changes that are incompatible with a stable dimerisation interface. Thus, our view that the native mitochondrial ADP/ATP carrier exists and functions as a monomer remains unaltered.

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