scholarly journals Unpacking Pandora from Its Box: Deciphering the Molecular Basis of the SARS-CoV-2 Coronavirus

2020 ◽  
Vol 22 (1) ◽  
pp. 386
Author(s):  
Valerie Bríd O’Leary ◽  
Oliver James Dolly ◽  
Cyril Höschl ◽  
Marie Černa ◽  
Saak Victor Ovsepian
Keyword(s):  
Molecular Basis ◽  
Scientific Community ◽  
Open Reading Frames ◽  
Structural Proteins ◽  
Cellular Internalization ◽  
Loop Formation ◽  
Stem Loop ◽  
Viral Genomes ◽  
Glycosylation Sites ◽  
Reading Frames

An enigmatic localized pneumonia escalated into a worldwide COVID-19 pandemic from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This review aims to consolidate the extensive biological minutiae of SARS-CoV-2 which requires decipherment. Having one of the largest RNA viral genomes, the single strand contains the genes ORF1ab, S, E, M, N and ten open reading frames. Highlighting unique features such as stem-loop formation, slippery frameshifting sequences and ribosomal mimicry, SARS-CoV-2 represents a formidable cellular invader. Hijacking the hosts translational engine, it produces two polyprotein repositories (pp1a and pp1ab), armed with self-cleavage capacity for production of sixteen non-structural proteins. Novel glycosylation sites on the spike trimer reveal unique SARS-CoV-2 features for shielding and cellular internalization. Affording complexity for superior fitness and camouflage, SARS-CoV-2 challenges diagnosis and vaccine vigilance. This review serves the scientific community seeking in-depth molecular details when designing drugs to curb transmission of this biological armament.

scholarly journals Sorting the diverse: The sequencebased classifications of carbohydrateactive enzymes

2008 ◽  
Vol 30 (4) ◽  
pp. 26-32 ◽  
Author(s):  
Gideon J. Davies ◽  
Michael L. Sinnott
Keyword(s):  
Cell Biology ◽  
Scientific Community ◽  
Cellular Communication ◽  
Chemical Diversity ◽  
Open Reading Frames ◽  
Glycoside Hydrolases ◽  
Major Goal ◽  
Reading Frames ◽  
Storage Starch ◽  
Modular Nature

Carbohydrates offer a structural and chemical diversity unrivalled in Nature: two glucose residues can be joined together in 30 different ways, and, with six different sugars, the number of possible isomers exceeds 1012 [1]. This huge diversity is reflected in the diverse roles for carbohydrates in Nature. Mono, di, oligo and polysaccharides and glycoconjugates play myriad roles in biology, in addition to wellknown ones such as energy storage (starch, glycogen) and maintenance of structure (cellulose, chitin, alginate). The diversity of what is sometimes called the ‘glycome’ also provides for a subtle means of cellular communication in higher organisms: carbohydrates are the language of the cell. Sugarmediated interactions not only are important for the communication of healthy cells, but also play crucial roles in disease, viral invasion and bacterial attack and malignancy. Sharon [2] has termed the challenge of carbohydrates as “the last frontier of molecular and cell biology”. There is thus considerable interest in the enzymes whose job it is to modify and cleave carbohydrates [GHs (glycoside hydrolases) and lyases] and those involved in their biosynthesis, GTs (glycosyltransferases). Typically, these enzymes make up approx. 1–2% of the genome of any organism [3]. Thus, at the time of writing, there are around 70000 ORFs (open reading frames) known which potentially encode GHs or GTs. A major goal for the scientific community is to extract useful informa tion on the enzymes encoded by these ORFs from sequence alone. This is an enormous challenge, one complicated by the modular nature of the enzymes themselves [4].

scholarly journals Overexpression of 7a, a Protein Specifically Encoded by the Severe Acute Respiratory Syndrome Coronavirus, Induces Apoptosis via a Caspase-Dependent Pathway

2004 ◽  
Vol 78 (24) ◽  
pp. 14043-14047 ◽  
Author(s):  
Yee-Joo Tan ◽  
Burtram C. Fielding ◽  
Phuay-Yee Goh ◽  
Shuo Shen ◽  
Timothy H. P. Tan ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Cell Lines ◽  
Cellular Localization ◽  
Viral Proteins ◽  
Open Reading Frames ◽  
Structural Proteins ◽  
Dependent Pathway ◽  
Reading Frames ◽  
Viral Structural Proteins

ABSTRACT Besides genes that are homologous to proteins found in other coronaviruses, the severe acute respiratory syndrome coronavirus genome also contains nine other potential open reading frames. Previously, we have characterized the expression and cellular localization of two of these “accessory” viral proteins, 3a (previously termed U274) and 7a (previously termed U122). In this study, we further examined whether they can induce apoptosis, which has been observed clinically. We showed that the overexpression of 7a, but not of 3a or the viral structural proteins, nucleocapsid, membrane, and envelope, induces apoptosis. 7a induces apoptosis via a caspase-dependent pathway and in cell lines derived from different organs, including lung, kidney, and liver.

scholarly journals Mapping the Non-Structural Transmembrane Proteins of SARS-CoV-2

2020 ◽  
Author(s):  
Sunil Thomas
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Drug Targets ◽  
Transmembrane Proteins ◽  
Host Immunity ◽  
Open Reading Frames ◽  
Structural Proteins ◽  
Wild Animals ◽  
Cell Organelles ◽  
Enveloped Virus ◽  
Reading Frames

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the disease COVID-19 has wreaked havoc on the health and economy of humanity. In addition, the disease is observed in domestic and wild animals. The disease has impacted directly and indirectly every corner of the planet. Currently, there are no vaccines and effective therapies for COVID-19. SARS-CoV-2 is an enveloped virus with a single-stranded RNA genome of 29.8 kb. More than two-thirds of the genome comprises Orf1ab encoding 16 non-structural proteins (nsps) followed by mRNAs encoding structural proteins, spike (S), envelop (E), membrane (M), and nucleocapsid (N). These genes are interspaced with several accessory genes (open reading frames [Orf] 3a, 3b, 6, 7a, 7b, 8, 9b, 9c and 10). The functions of these proteins are of particular interest for understanding the pathogenesis of SARS-CoV-2. Several of the nsps (nsp3, nsp4, nsp6) and Orf3a are transmembrane proteins involved in regulating the host immunity, modifying host cell organelles for viral replication and escape and hence considered drug targets. In this paper we report mapping the transmembrane structure of the non-structural proteins of SARS-CoV-2.

Chargaff difference analysis of the bithorax complex of Drosophila melanogaster

1998 ◽  
Vol 76 (1) ◽  
pp. 129-137 ◽  
Author(s):  
Kha D Dang ◽  
Previn B Dutt ◽  
Donald R Forsdyke
Keyword(s):  
Fruit Fly ◽  
Open Reading Frames ◽  
Bithorax Complex ◽  
Stem Loop ◽  
Difference Analysis ◽  
Template Strand ◽  
A Genome ◽  
Dna Strand ◽  
The Right ◽  
Reading Frames

Much of the fruit fly genome is compact ("Escherichia coli mode"), indicating a genome-wide selection pressure against DNA with little adaptive function. However, in the bithorax complex (BX-C) homeodomain genes are widely dispersed with large introns ("mammalian mode"). Chargaff difference analysis of compact bacterial and viral genomes has shown that most mRNAs have the potential to form stem-loop structures with purine-rich loops. Thus, for many taxa if transcription is to the right, the top (mRNA synonymous) DNA strand has purine-rich loop potential, and if transcription is to the left, the top (template) strand has pyrimidine-rich loop potential. The best indicator bases for transcription direction are A and T for AT-rich genomes, and C and G for CG-rich genomes. Consistent with this, Chargaff difference analysis of BX-C genes and several non-BX-C genes shows that, whatever the mode, mRNAs have the potential to form stem-loop structures with A-rich loops. We confirm that many potential open reading frames in the BX-C are unlikely to be functional. Conversely, we suggest that a few unassigned open reading frames may actually be functional. Since apparent organization in the mammalian mode cannot be explained in terms of unacknowledged open reading frames, yet the fruit fly genome is under pressure to be compact, it is likely that many BX-C functions do not involve the encoding of proteins.Key words: base ratios, base clusters, Chargaff's second parity rule, open reading frames, transcription direction, stem-loops.

scholarly journals Identification of Trichoplusia ni ascovirus 2c virion structural proteins

2007 ◽  
Vol 88 (8) ◽  
pp. 2194-2197 ◽  
Author(s):  
Liwang Cui ◽  
Xiaowen Cheng ◽  
Lianchao Li ◽  
Jianyong Li
Keyword(s):  
Mass Spectrometry ◽  
Trichoplusia Ni ◽  
Major Capsid Protein ◽  
Protein Sequences ◽  
Open Reading Frames ◽  
Structural Proteins ◽  
Tandem Mass ◽  
Double Stranded Dna ◽  
Coomassie Blue ◽  
Reading Frames

Ascoviruses are a family of insect viruses with circular, double-stranded DNA genomes. With the sequencing of the Trichoplusia ni ascovirus 2c (TnAV-2c) genome, the virion structural proteins were identified by using tandem mass spectrometry. From at least eight protein bands visible on a Coomassie blue-stained gel of TnAV-2c virion proteins, seven bands generated protein sequences that matched predicted open reading frames (ORFs) in the genome, i.e. ORFs 2, 43, 115, 141, 142, 147 and 153. Among these ORFs, only ORF153, encoding the major capsid protein, has been characterized previously.

scholarly journals Molecular Characterization of IS1541Insertions in the Genome of Yersinia pestis

1998 ◽  
Vol 180 (1) ◽  
pp. 178-181 ◽  
Author(s):  
Monique Odaert ◽  
Annie Devalckenaere ◽  
Patrick Trieu-Cuot ◽  
Michel Simonet
Keyword(s):  
Yersinia Pestis ◽  
Hot Spots ◽  
Insertion Sequence ◽  
Single Copy ◽  
Open Reading Frames ◽  
Stem Loop ◽  
Insertion Sites ◽  
Flanking Regions ◽  
Reading Frames

ABSTRACT The genome of Yersinia pestis, the causative agent of plague, contains at least 30 copies of an element, designated IS1541, which is structurally related to IS200(85% identity). One such element is inserted within the chromosomalinv gene (M. Simonet, B. Riot, N. Fortineau, and P. Berche, Infect. Immun. 64:375–379, 1996). We characterized other IS1541 insertions by cloning 14 different Y. pestis 6/69M loci carrying a single copy of this insertion sequence (IS) into Escherichia coli and, for each element, sequencing 250 bp of both flanking regions. In no case was this IS element inserted into large open reading frames; however, in eight cases, it was detected downstream (17 to 139 bp) of genes thought to be transcribed monocistronically or which constituted the last gene of an operon, and in only one case was it detected upstream (37 bp) of the first gene of an operon. Sequence analysis revealed stem-loop structures (ΔG, <−10 kcal) resembling rho-independent transcription terminators in 8 of the 14 insertion sites. These motifs might constitute hot spots for insertion of this IS1541element within the Y. pestis genome.

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.

Molecular characterization of the genome of a partitivirus from the basidiomycete Rhizoctonia solani

Microbiology ◽  
2000 ◽  
Vol 81 (2) ◽  
pp. 549-555 ◽  
Author(s):  
Ethan E. Strauss ◽  
Dilip K. Lakshman ◽  
Stellos M. Tavantzis
Keyword(s):  
Rhizoctonia Solani ◽  
Molecular Mass ◽  
Rna Virus ◽  
Open Reading Frames ◽  
Stem Loop ◽  
Subgenomic Rna ◽  
Atkinsonella Hypoxylon ◽  
Coding Potential ◽  
Reading Frames

The bisegmented genome of a double-stranded (ds) RNA virus from the fungus Rhizoctonia solani isolate Rhs 717 was characterized. The larger segment, dsRNA 1, is 2363 bases long whereas the smaller segment, dsRNA 2, has 2206 bases. The 5′ ends of the coding strands of dsRNA 1 and dsRNA 2 are highly conserved (100% identity over 47 bases), and contain inverted repeats capable of forming stable stem–loop structures. Analysis of the coding potential of each of the two segments showed that dsRNAs 1 and 2 could code for polypeptides of 730 aa (bases 86–2275; molecular mass 86 kDa) and 683 aa (bases 79–2130; molecular mass 76 kDa), respectively. The 86 kDa polypeptide has all the motifs of dsRNA RNA-dependent RNA polymerases (RDRP), and has significant homology with putative RDRPs of partitiviruses from Fusarium poae and Atkinsonella hypoxylon. The 76 kDa protein shows homology with the putative capsid proteins (CP) of the same viruses. Northern blot analysis revealed no subgenomic RNA species, consistent with the fact that the long open reading frames encoding the putative RDRP and CP cover the entire length of the respective dsRNAs.

scholarly journals Isolation and characterization of Israeli acute paralysis virus, a dicistrovirus affecting honeybees in Israel: evidence for diversity due to intra- and inter-species recombination

2007 ◽  
Vol 88 (12) ◽  
pp. 3428-3438 ◽  
Author(s):  
Eyal Maori ◽  
Shai Lavi ◽  
Rita Mozes-Koch ◽  
Yulia Gantman ◽  
Yuval Peretz ◽  
...  
Keyword(s):  
Information Exchange ◽  
Open Reading Frames ◽  
Stem Loop ◽  
Israeli Acute Paralysis Virus ◽  
Isolation And Characterization ◽  
Kashmir Bee Virus ◽  
Acute Bee Paralysis Virus ◽  
Paralysis Virus ◽  
Reading Frames

We report the isolation, purification, genome-sequencing and characterization of a picorna-like virus from dead bees in Israel. Sequence analysis indicated that IAPV (Israeli acute paralysis virus) is a distinct dicistrovirus. It is most homologous to Kashmir bee virus and acute bee paralysis virus. The virus carries a 9487 nt RNA genome in positive orientation, with two open reading frames separated by an intergenic region, and its coat comprises four major proteins, the sizes of which suggest alternate processing of the polyprotein. IAPV virions also carry shorter, defective-interfering (DI)-like RNAs. Some of these RNAs are recombinants of different segments of IAPV RNA, some are recombinants of IAPV RNA and RNA from another dicistrovirus, and yet others are recombinants of IAPV and non-viral RNAs. In several of the DI-like RNAs, a sense-oriented fragment has recombined with its complement, forming hairpins and stem–loop structures. In previous reports, we have shown that potyviral and IAPV sequences are integrated into the genome of their respective hosts. The dynamics of information exchange between virus and host and the possible resistance-engendering mechanisms are discussed.

scholarly journals Characterization of Nora Virus Structural Proteins via Western Blot Analysis

Scientifica ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Brad L. Ericson ◽  
Darby J. Carlson ◽  
Kimberly A. Carlson
Keyword(s):  
Western Blot ◽  
Open Reading Frames ◽  
Structural Proteins ◽  
Polypeptide Composition ◽  
Virus Particles ◽  
E Coli ◽  
Nora Virus ◽  
Monospecific Antisera ◽  
Reading Frames

Nora virus is a single stranded RNA picorna-like virus with four open reading frames (ORFs). The coding potentials of the ORFs are not fully characterized, but ORF3 and ORF4 are believed to encode the capsid proteins (VP3, VP4a, VP4b, and VP4c) comprising the virion. To determine the polypeptide composition of Nora virus virions, polypeptides from purified virus were compared to polypeptides detected in Nora virus infectedDrosophila melanogaster. Nora virus was purified from infected flies and used to challenge mice for the production of antisera.ORF3,ORF4a,ORF4b, andORF4cwere individually cloned and expressed inE. coli; resultant recombinant proteins purified and were used to make monospecific antisera. Antisera were evaluated via Western blot against whole virus particles and Nora virus infected fly lysates. Viral purification yielded two particle types with densities of ~1.31 g/mL (empty particles) and ~1.33 g/mL (complete virions). Comparison of purified virus polypeptide composition to Nora virus infectedD. melanogasterlysate showed the number of proteins in infected cell lysates is less than purified virus. Our results suggest the virion is composed of 6 polypeptides, VP3, VP4a, two forms of VP4b, and two forms of VP4c. This polypeptide composition is similar to other small RNA insect viruses.

Sign in / Sign up

Export Citation Format

Share Document