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 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.

scholarly journals The SARS-CoV-2 antibody landscape is lower in magnitude for structural proteins, diversified for accessory proteins and stable long-term in children

2021 ◽  
Author(s):  
Asmaa Hachim ◽  
Haogao Gu ◽  
Otared Kavian ◽  
Mike YW Kwan ◽  
Wai-hung Chan ◽  
...  
Keyword(s):  
Antibody Response ◽  
Principal Component ◽  
Humoral Response ◽  
Open Reading Frames ◽  
Clinical Severity ◽  
Structural Proteins ◽  
Accessory Proteins ◽  
Longitudinal Sampling ◽  
Reading Frames

AbstractBackgroundChildren are less clinically affected by SARS-CoV-2 infection than adults with the majority of cases being mild or asymptomatic and the differences in infection outcomes are poorly understood. The kinetics, magnitude and landscape of the antibody response may impact the clinical severity and serological diagnosis of COVID-19. Thus, a comprehensive investigation of the antibody landscape in children and adults is needed.MethodsWe tested 254 plasma from 122 children with symptomatic and asymptomatic SARS-CoV-2 infections in Hong Kong up to 206 days post symptom onset, including 146 longitudinal samples from 58 children. Adult COVID-19 patients and pre-pandemic controls were included for comparison. We assessed antibodies to a 14-wide panel of SARS-CoV-2 structural and accessory proteins by Luciferase Immunoprecipitation System (LIPS).FindingsChildren have lower levels of Spike and Nucleocapsid antibodies than adults, and their cumulative humoral response is more expanded to accessory proteins (NSP1 and Open Reading Frames (ORFs)). Sensitive serology using the three N, ORF3b, ORF8 antibodies can discriminate COVID-19 in children. Principal component analysis revealed distinct serological signatures in children and the highest contribution to variance were responses to non-structural proteins ORF3b, NSP1, ORF7a and ORF8. Longitudinal sampling revealed maintenance or increase of antibodies for at least 6 months, except for ORF7b antibodies which showed decline. It was interesting to note that children have higher antibody responses towards known IFN antagonists: ORF3b, ORF6 and ORF7a. The diversified SARS-CoV-2 antibody response in children may be an important factor in driving control of SARS-CoV-2 infection.

scholarly journals Genes of SARS-CoV-2 and emerging variants

2021 ◽  
Vol 42 (1) ◽  
pp. 10
Author(s):  
Sudip Dhakal ◽  
Ian Macreadie
Keyword(s):  
Viral Entry ◽  
Host Cells ◽  
Structural Proteins ◽  
Accessory Proteins ◽  
Proper Understanding ◽  
Recent Emergence ◽  
Genes Encoding ◽  
Rapid Transmission ◽  
Host Defence System ◽  
Human Coronaviruses

The pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is distinctly different from outbreaks caused by other coronaviruses: SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). The differences in the rapid transmission and severity of human coronaviruses are due to the genetic composition of the virus. SARS-CoV-2 contains genes encoding non-structural proteins (NSPs), structural proteins, and accessory proteins. The NSPs are mainly involved in replication of the virus within the host and inhibition of the host defence system. Structural proteins are involved in viral entry and attachment to host cells, preservation of the core virion and elicit the majority of the immune response. The functions of the accessory proteins are largely unknown. Most focus has been given to structural proteins, especially the spike protein as the strongest vaccine candidate. However, the recent emergence of spike variants and their ability to rapidly transmit and escape neutralisation by vaccine-induced antibodies has threatened the global community. Meanwhile, recent studies of accessory proteins reveal their importance in viral pathogenesis. Hence, proper understanding of the functions of all unknown viral proteins is crucial to devise alternate antiviral strategies.

scholarly journals Isolation and Characterization of Salmonella Jumbo-Phage pSal-SNUABM-04

Viruses ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 27
Author(s):  
Jun Kwon ◽  
Sang Guen Kim ◽  
Hyoun Joong Kim ◽  
Sib Sankar Giri ◽  
Sang Wha Kim ◽  
...  
Keyword(s):  
Morphological Traits ◽  
Open Reading Frames ◽  
Genome Comparison ◽  
The Novel ◽  
Promising Alternative ◽  
Isolation And Characterization ◽  
Global Issue ◽  
Reading Frames ◽  
Predicted Function

The increasing emergence of antimicrobial resistance has become a global issue. Therefore, many researchers have attempted to develop alternative antibiotics. One promising alternative is bacteriophage. In this study, we focused on a jumbo-phage infecting Salmonella isolated from exotic pet markets. Using a Salmonella strain isolated from reptiles as a host, we isolated and characterized the novel jumbo-bacteriophage pSal-SNUABM-04. This phage was investigated in terms of its morphology, host infectivity, growth and lysis kinetics, and genome. The phage was classified as Myoviridae based on its morphological traits and showed a comparatively wide host range. The lysis efficacy test showed that the phage can inhibit bacterial growth in the planktonic state. Genetic analysis revealed that the phage possesses a 239,626-base pair genome with 280 putative open reading frames, 76 of which have a predicted function and 195 of which have none. By genome comparison with other jumbo phages, the phage was designated as a novel member of Machinavirus composed of Erwnina phages.

scholarly journals A successful use of a new shuttle cloning vector pA13 for the cloning of the bacteriocins BacSJ and acidocin 8912

2010 ◽  
Vol 62 (2) ◽  
pp. 231-243 ◽  
Author(s):  
Milan Kojic ◽  
Jelena Lozo ◽  
B. Jovcic ◽  
Ivana Strahinic ◽  
D. Fira ◽  
...  
Keyword(s):  
In Silico Analysis ◽  
Functional Expression ◽  
Open Reading Frames ◽  
Cloning Vector ◽  
The Novel ◽  
Genetic Manipulations ◽  
Genes Encoding ◽  
Editorial Decision ◽  
Terminal Amino

The aim of this paper was to research the molecular cloning of genes encoding the novel bacteriocin BacSJ from Lactobacillus paracasei subsp. paracasei BGSJ2-8 by using a newly constructed shuttle cloning vector pA13. A new shuttle-cloning vector, pA13, was constructed and successfully introduced into Escherichia coli, Lactobacillus and Lactococcus strains, showing a high segregational and structural stability in all three hosts. The natural plasmid pSJ2-8 from L. paracasei subsp. paracasei BGSJ2-8 was cloned in the pA13 using BamHI, obtaining the construct pB5. Sequencing and in silico analysis of the pB5 revealed 15 open reading frames (ORF). Plasmid pSJ2-8 harbors the genes encoding the production of two bacteriocins, BacSJ and acidocin 8912. The combined N-terminal amino acid sequencing of BacSJ in combination with DNA sequencing of the bacSJ2-8 gene enabled the determination of the primary structure of a bacteriocin BacSJ. The production and functional expression of BacSJ in homologous and heterologous hosts suggest that bacSJ2-8 and bacSJ2-8i together with the genes encoding the ABC transporter and accessory protein are the minimal requirement for the production of BacSJ. Biochemical and genetic analyses showed that BacSJ belongs to the class II bacteriocins. The shuttle cloning vector pA13 could be used as a tool for genetic manipulations in lactobacilli and lactococci. <br><br><b><font color="red">withdrawn; due to a printing error. Link to the Editorial Decision <u><a href="http://dx.doi.org/10.2298/ABS1004251U">10.2298/ABS1004251U</a></u></font></b><br>

scholarly journals The Novel Agrotis ipsilon Nora Virus Confers Deleterious Effects to the Fitness of Spodoptera frugiperda (Lepidoptera: Noctuidae)

2021 ◽  
Vol 12 ◽  
Author(s):  
Tong Li ◽  
Ruobing Guan ◽  
Yuqing Wu ◽  
Su Chen ◽  
Guohui Yuan ◽  
...  
Keyword(s):  
Spodoptera Frugiperda ◽  
Rna Virus ◽  
Open Reading Frames ◽  
Agrotis Ipsilon ◽  
The Novel ◽  
Black Cutworm ◽  
A Genome ◽  
Nora Virus ◽  
Novel Host ◽  
Lepidoptera Noctuidae

In the present study, we identified a novel, positive-sense single-stranded RNA virus in the Chinese black cutworm, Agrotis ipsilon. It has a genome length of 11,312 nucleotides, excluding the poly(A) tails, and contains five open reading frames. The ORF2 encodes the conserved domains of RNA helicase and RNA-dependent RNA polymerase, while ORF4 and 5 encode three viral proteins. Herein, the A. ipsilon virus was clustered with a Helicoverpa armigera Nora virus and was thus provisionally named “Agrotis ipsilon Nora virus” (AINV). AINV was successfully transmitted into a novel host, Spodoptera frugiperda, through injection, causing a stable infection. This found the possibility of horizontal AINV transmission among moths belonging to the same taxonomic family. Nonetheless, AINV infection was deleterious to S. frugiperda and mainly mediated by antiviral and amino acid metabolism-related pathways. Furthermore, the infection significantly increased the S. frugiperda larval period but significantly reduced its moth eclosion rate. It suggests that AINV is probably to be a parasitic virus of S. frugiperda.

scholarly journals SARS-CoV-2 escape in vitro from a highly neutralizing COVID-19 convalescent plasma

2020 ◽  
Author(s):  
Emanuele Andreano ◽  
Giulia Piccini ◽  
Danilo Licastro ◽  
Lorenzo Casalino ◽  
Nicole V. Johnson ◽  
...  
Keyword(s):  
South Africa ◽  
Immune Response ◽  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Receptor Binding Domain ◽  
The United Kingdom ◽  
Effective Immune Response ◽  
Recent Emergence ◽  
Natural Variants

ABSTRACTTo investigate the evolution of SARS-CoV-2 in the immune population, we co-incubated authentic virus with a highly neutralizing plasma from a COVID-19 convalescent patient. The plasma fully neutralized the virus for 7 passages, but after 45 days, the deletion of F140 in the spike N-terminal domain (NTD) N3 loop led to partial breakthrough. At day 73, an E484K substitution in the receptor-binding domain (RBD) occurred, followed at day 80 by an insertion in the NTD N5 loop containing a new glycan sequon, which generated a variant completely resistant to plasma neutralization. Computational modeling predicts that the deletion and insertion in loops N3 and N5 prevent binding of neutralizing antibodies. The recent emergence in the United Kingdom and South Africa of natural variants with similar changes suggests that SARS-CoV-2 has the potential to escape an effective immune response and that vaccines and antibodies able to control emerging variants should be developed.One Sentence SummaryThree mutations allowed SARS-CoV-2 to evade the polyclonal antibody response of a highly neutralizing COVID-19 convalescent plasma.

Tailoring Polymer Surfaces for Controlled Cell Behavior

1998 ◽  
Vol 530 ◽  
Author(s):  
A.M. Mayes ◽  
D.J. Irvine ◽  
L.G. Griffith
Keyword(s):  
Protein Adsorption ◽  
Surface Segregation ◽  
Cell Attachment ◽  
Model Systems ◽  
Protein Resistance ◽  
Small Proteins ◽  
Novel Approach ◽  
Poly Ethylene ◽  
Comb Copolymer ◽  
Adhesion Ligand

AbstractAn ideal surface for many biomaterials applications would resist nonspecific protein adsorption while at the same time providing a means for specifically signaling cells to guide survival, growth, migration, and differentiation. This work was directed towards the investigation of model systems and clinically-applicable materials which provide both of these surface requirements. Model systems were prepared by chemically grafting end-functionalized star poly(ethylene oxide) (PEO) to surfaces. The end-grafted polymers provide a means for cell-signaling through coupling of peptides to the free chain ends. Protein adsorption on star vs. linear grafted layers was compared. To further understand these results, neutron reflectivity studies were carried out in situ for solvated PEO surfaces to determine the concentration profiles of the swollen grafted layers. Surprisingly, grafted PEO layers which resist protein adsorption have low concentrations of polymer segments throughout the swollen layer. We find that dense star architectures which might be expected to impart improved protein resistance in fact allow small proteins to adsorb. For clinical materials, a novel approach to the surface modification of poly(lactide) (PLA) has been taken by surface segregating a comb copolymer containing a PLA backbone and poly(ethylene glycol) teeth. The ends of the teeth provide sites for surface tethering of peptide ligands. Comb surfaces without tethered ligands are cell adhesion resistant, indicating strong protein adsorption resistance. By then incorporating an adhesion ligand, modulation of cell morphology on comb surfaces has been demonstrated. Finally, the surface segregation of the comb to the surface of PLA was shown via cell attachment assays and XPS measurements.

scholarly journals Proteolytic Processing of Sapovirus ORF1 Polyprotein

2005 ◽  
Vol 79 (12) ◽  
pp. 7283-7290 ◽  
Author(s):  
Tomoichiro Oka ◽  
Kazuhiko Katayama ◽  
Satoko Ogawa ◽  
Grant S. Hansman ◽  
Tsutomu Kageyama ◽  
...  
Keyword(s):  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Proteolytic Processing ◽  
Open Reading Frames ◽  
Rabbit Hemorrhagic Disease Virus ◽  
Translation System ◽  
Hemorrhagic Disease ◽  
Rabbit Hemorrhagic Disease ◽  
Capsid Protein Vp1

ABSTRACT The genome of Sapovirus (SaV), a causative agent of gastroenteritis in humans and swine, contains either two or three open reading frames (ORFs). Functional motifs characteristic to the 2C-like NTPase (NTPase), VPg, 3C-like protease (Pro), 3D-like RNA-dependent RNA polymerase (Pol), and capsid protein (VP1) are encoded in the ORF1 polyprotein, which is afterwards cleaved into the nonstructural and structural proteins. We recently determined the complete genome sequence of a novel human SaV strain, Mc10, which has two ORFs. To investigate the proteolytic cleavage of SaV ORF1 and the function of protease on the cleavage, both full-length and truncated forms of the ORF1 polyprotein either with or without mutation in 1171Cys to Ala of the GDCG motif were expressed in an in vitro coupled transcription-translation system. The translation products were analyzed directly by sodium dodecyl sulfate-polyacrylamide gel electrophoresis or by immunoprecipitation with region-specific antibodies. The ORF1 polyprotein was processed into at least 10 major proteins: p11, p28, p35, p32, p14, p70, p60, p66, p46, and p120. Seven of these products were arranged in the following order: NH2-p11-p28-p35(NTPase)-p32-p14(VPg)-p70(Pro-Pol)-p60(VP1)-COOH. p66, p46 and p120 were precursors of p28-p35 (NTPase), p32-p14 (VPg), and p32-p14 (VPg)-p70 (Pro-Pol), respectively. Mutagenesis in the 3C-like protease motif fully abolished the proteolytic activity. The cleavage map of SaV ORF1 is similar to those of other heretofore known members of the family Caliciviridae, especially to rabbit hemorrhagic disease virus, a member of the genus Lagovirus.

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