scholarly journals Evolutionary Insights into the Envelope Protein of SARS-CoV-2

Author(s):  
M. Shaminur Rahman ◽  
M. Nazmul Hoque ◽  
M. Rafiul Islam ◽  
Israt Islam ◽  
Israt Dilruba Mishu ◽  
...  

The ongoing mutations in the structural proteins of SARS-CoV-2 is the major impediment for prevention and control of the COVID-19 disease. The envelope (E) protein of SARS-CoV-2 is a structural protein existing in both monomeric and homopentameric forms, associated with a multitude of functions including virus assembly, replication, dissemination, release of virions, infection, pathogenesis, and immune response stimulation. In the present study, 81,818 high quality E protein sequences retrieving from the GISAID were subjected to mutational analyses. Our analysis revealed that only 0.012 % (982/81818) stains possessed amino acid (aa) substitutions in 63 sites of the genome while 58.77% mutations in the primary structure of nucleotides in 134 sites. We found the V25A mutation in the transmembrane domain which is a key factor for the homopentameric conformation of E protein. We also observed a triple cysteine motif harboring mutations (L39M, A41S, A41V, C43F, C43R, C43S, C44Y, N45R) which may hinder the binding of E protein with spike glycoprotein. These results therefore suggest the continuous monitoring of each structural protein of SARS-CoV-2 since the number of genome sequences from across the world are continuously increasing.

2020 ◽  
Vol 94 (14) ◽  
Author(s):  
Anja Dalmann ◽  
Ilona Reimann ◽  
Kerstin Wernike ◽  
Martin Beer

ABSTRACT Autonomously replicating subgenomic Bungowannah virus (BuPV) RNAs (BuPV replicons) with deletions of the genome regions encoding the structural proteins C, ERNS, E1, and E2 were constructed on the basis of an infectious cDNA clone of BuPV. Nanoluciferase (Nluc) insertion was used to compare the replication efficiencies of all constructs after electroporation of in vitro-transcribed RNA from the different clones. Deletion of C, E1, E2, or the complete structural protein genome region (C-ERNS-E1-E2) prevented the production of infectious progeny virus, whereas deletion of ERNS still allowed the generation of infectious particles. However, those ΔERNS viral particles were defective in virus assembly and/or egress and could not be further propagated for more than three additional passages in porcine SK-6 cells. These “defective-in-third-cycle” BuPV ΔERNS mutants were subsequently used to express the classical swine fever virus envelope protein E2, the N-terminal domain of the Schmallenberg virus Gc protein, and the receptor binding domain of the Middle East respiratory syndrome coronavirus spike protein. The constructs could be efficiently complemented and further passaged in SK-6 cells constitutively expressing the BuPV ERNS protein. Importantly, BuPVs are able to infect a wide variety of target cell lines, allowing expression in a very wide host spectrum. Therefore, we suggest that packaged BuPV ΔERNS replicon particles have potential as broad-spectrum viral vectors. IMPORTANCE The proteins NPRO and ERNS are unique for the genus Pestivirus, but only NPRO has been demonstrated to be nonessential for in vitro growth. While this was also speculated for ERNS, it has always been previously shown that pestivirus replicons with deletions of the structural proteins ERNS, E1, or E2 did not produce any infectious progeny virus in susceptible host cells. Here, we demonstrated for the first time that BuPV ERNS is dispensable for the generation of infectious virus particles but still important for efficient passaging. The ERNS-defective BuPV particles showed clearly limited growth in cell culture but were capable of several rounds of infection, expression of foreign genes, and highly efficient trans-complementation to rescue virus replicon particles (VRPs). The noncytopathic characteristics and the absence of preexisting immunity to BuPV in human populations and livestock also provide a significant benefit for a possible use, e.g., as a vector vaccine platform.


2004 ◽  
Vol 78 (23) ◽  
pp. 13019-13027 ◽  
Author(s):  
Roeland Wieringa ◽  
Antoine A. F. de Vries ◽  
Jannes van der Meulen ◽  
Gert-Jan Godeke ◽  
Jos J. M. Onderwater ◽  
...  

ABSTRACT Equine arteritis virus (EAV) is an enveloped, positive-stranded RNA virus belonging to the family Arteriviridae of the order Nidovirales. EAV particles contain seven structural proteins: the nucleocapsid protein N, the unglycosylated envelope proteins M and E, and the N-glycosylated membrane proteins GP2b (previously named GS), GP3, GP4, and GP5 (previously named GL). Proteins N, M, and GP5 are major virion components, E occurs in virus particles in intermediate amounts, and GP4, GP3, and GP2b are minor structural proteins. The M and GP5 proteins occur in virus particles as disulfide-linked heterodimers while the GP4, GP3, and GP2b proteins are incorporated into virions as a heterotrimeric complex. Here, we studied the effect on virus assembly of inactivating the structural protein genes one by one in the context of a (full-length) EAV cDNA clone. It appeared that the three major structural proteins are essential for particle formation, while the other four virion proteins are dispensable. When one of the GP2b, GP3, or GP4 proteins was missing, the incorporation of the remaining two minor envelope glycoproteins was completely blocked while that of the E protein was greatly reduced. The absence of E entirely prevented the incorporation of the GP2b, GP3, and GP4 proteins into viral particles. EAV particles lacking GP2b, GP3, GP4, and E did not markedly differ from wild-type virions in buoyant density, major structural protein composition, electron microscopic appearance, and genomic RNA content. On the basis of these results, we propose a model for the EAV particle in which the GP2b/GP3/GP4 heterotrimers are positioned, in association with a defined number of E molecules, above the vertices of the putatively icosahedral nucleocapsid.


2020 ◽  
Vol 2020 (2) ◽  
Author(s):  
Stephen P.H. Alexander ◽  
Jonathan K. Ball ◽  
Theocharis Tsoleridis

CoronavirusesCoronaviruses are large, often spherical, enveloped, single-stranded positive-sense RNA viruses, ranging in size from 80-220 nm. Of the four structural proteins encoded in the viral genome, the RNA winds around the highly basic nucleocapsid (N) protein. The three other structural proteins, envelope (E), membrane (M) and spike (S), are transmembrane proteins. The E protein is a small (9-12 kDa) single transmembrane domain protein, which enables virus assembly with the M protein, a larger (23-35 kDa) 3TM protein. Coronaviruses are named for the crown-shaped appearance of the virus due to the large (120+ kDa) S spike 1TM glycoprotein, which forms extended homotrimers. The spike protein binds to the animal host cell by interacting with specific anchoring proteins, typically proteinases, such as angiotensin-converting enzyme 2 or aminopeptidase N. This binding facilitates viral entry into the cell and the release of the genome. Aside from the four structural proteins, the remainder of the genome encodes accessory or non-structural proteins and includes proteinases to cleave the two encoded polyproteins. The remainder of the genome encodes elements for viral replication, assembly and release, as well as proteins which manipulate the host's innate immune system.


2016 ◽  
Vol 45 (2) ◽  
pp. 28-48 ◽  
Author(s):  
Isaac Dery

Women’s access to and control over productive resources, including land, has increasingly been recognized in global discussions as a key factor in reducing poverty, ensuring food security and promoting gender equality. Indeed, this argument has been widely accepted by both feminists and development theorists since the 1980s. Based on qualitative research with 50 purposively selected men and women, this study explored the complexity of women’s access to and control over land within a specific relationship of contestations, negotiations, and manipulations with men. Data were analyzed using thematic analysis. While theoretically, participants showed that women’s [secure] access to and control over land has beneficial consequences to women themselves, households and the community at large, in principle, women's access and control status was premised in the traditional framework which largely deprives women, equal access and/or control over the land. The study indicates that even though land is the most revered resource and indeed, the dominant source of income for the rural poor, especially women, gender-erected discrimination and exclusion lie at the heart of many rural women in gaining access to land. This study argues that women's weak access rights and control over land continue to perpetuate the feminization of gender inequality–while men were reported to possess primary access and control over land as the heads of households, women were argued to have secondary rights due to their ‘stranger statuses’ in their husbands’ families. Overall, the degree of access to land among women was reported to be situated within two broad contexts–marriage and inheritance.


Undoubtedly is a technological revolution that has certainly focused on the interest of software development companies, companies of IT, hardware design, networks and artificial intelligence. A technological revolution that started a few years ago and has evolved rapidly, thanks to the technological evolution of IT and networks. It is a combination of many communication protocols, sensors and other intelligent technologies, the correlation between smart technologies, networks and services that all together complete processes in order to achieve the result for which they were installed. In advanced technology countries, both simple users and industry use IoT where sensors are simplified and automated at home and in industry, there is continuous monitoring, control and prediction of product failure for the benefit of efficient production of high quality products and control production at each stage of product processing / production. Someone could well think and say that all this is fantastic and that we have solved the problem of organization, easy life without further thoughts and worries since everything is done automatically.An IoT in an intelligent house could literally regulate everything, using sensors and appropriate software could talk with a human person, as well as someone could appropriately entice all that security and literally take full control of the premises of a home with consequences from minimal to catastrophic including the complete destruction of a home.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexander Pralow ◽  
Alexander Nikolay ◽  
Arnaud Leon ◽  
Yvonne Genzel ◽  
Erdmann Rapp ◽  
...  

AbstractHere, we present for the first time, a site-specific N-glycosylation analysis of proteins from a Brazilian Zika virus (ZIKV) strain. The virus was propagated with high yield in an embryo-derived stem cell line (EB66, Valneva SE), and concentrated by g-force step-gradient centrifugation. Subsequently, the sample was proteolytically digested with different enzymes, measured via a LC–MS/MS-based workflow, and analyzed in a semi-automated way using the in-house developed glyXtoolMS software. The viral non-structural protein 1 (NS1) was glycosylated exclusively with high-mannose structures on both potential N-glycosylation sites. In case of the viral envelope (E) protein, no specific N-glycans could be identified with this method. Nevertheless, N-glycosylation could be proved by enzymatic de-N-glycosylation with PNGase F, resulting in a strong MS-signal of the former glycopeptide with deamidated asparagine at the potential N-glycosylation site N444. This confirmed that this site of the ZIKV E protein is highly N-glycosylated but with very high micro-heterogeneity. Our study clearly demonstrates the progress made towards site-specific N-glycosylation analysis of viral proteins, i.e. for Brazilian ZIKV. It allows to better characterize viral isolates, and to monitor glycosylation of major antigens. The method established can be applied for detailed studies regarding the impact of protein glycosylation on antigenicity and human pathogenicity of many viruses including influenza virus, HIV and corona virus.


2021 ◽  
Vol 22 (15) ◽  
pp. 8139
Author(s):  
Tomoko Tadokoro ◽  
Asahiro Morishita ◽  
Tsutomu Masaki

Remarkable progress has been made in the treatment and control of hepatitis B and C viral infections. However, fundamental treatments for diseases in which liver fibrosis is a key factor, such as cirrhosis, alcoholic/nonalcoholic steatohepatitis, autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis, are still under development and remain an unmet medical need. To solve this problem, it is essential to elucidate the pathogenesis of liver fibrosis in detail from a molecular and cellular perspective and to develop targeted therapeutic agents based on this information. Recently, microRNAs (miRNAs), functional RNAs of 22 nucleotides, have been shown to be involved in the pathogenesis of liver fibrosis. In addition, extracellular vesicles called “exosomes” have been attracting attention, and research is being conducted to establish noninvasive and extremely sensitive biomarkers using miRNAs in exosomes. In this review, we summarize miRNAs directly involved in liver fibrosis, miRNAs associated with diseases leading to liver fibrosis, and miRNAs related to complications of cirrhosis. We will also discuss the efficacy of each miRNA as a biomarker of liver fibrosis and pathology, and its potential application as a therapeutic agent.


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 821
Author(s):  
Rohitash Yadav ◽  
Jitendra Kumar Chaudhary ◽  
Neeraj Jain ◽  
Pankaj Kumar Chaudhary ◽  
Supriya Khanra ◽  
...  

Coronavirus belongs to the family of Coronaviridae, comprising single-stranded, positive-sense RNA genome (+ ssRNA) of around 26 to 32 kilobases, and has been known to cause infection to a myriad of mammalian hosts, such as humans, cats, bats, civets, dogs, and camels with varied consequences in terms of death and debilitation. Strikingly, novel coronavirus (2019-nCoV), later renamed as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and found to be the causative agent of coronavirus disease-19 (COVID-19), shows 88% of sequence identity with bat-SL-CoVZC45 and bat-SL-CoVZXC21, 79% with SARS-CoV and 50% with MERS-CoV, respectively. Despite key amino acid residual variability, there is an incredible structural similarity between the receptor binding domain (RBD) of spike protein (S) of SARS-CoV-2 and SARS-CoV. During infection, spike protein of SARS-CoV-2 compared to SARS-CoV displays 10–20 times greater affinity for its cognate host cell receptor, angiotensin-converting enzyme 2 (ACE2), leading proteolytic cleavage of S protein by transmembrane protease serine 2 (TMPRSS2). Following cellular entry, the ORF-1a and ORF-1ab, located downstream to 5′ end of + ssRNA genome, undergo translation, thereby forming two large polyproteins, pp1a and pp1ab. These polyproteins, following protease-induced cleavage and molecular assembly, form functional viral RNA polymerase, also referred to as replicase. Thereafter, uninterrupted orchestrated replication-transcription molecular events lead to the synthesis of multiple nested sets of subgenomic mRNAs (sgRNAs), which are finally translated to several structural and accessory proteins participating in structure formation and various molecular functions of virus, respectively. These multiple structural proteins assemble and encapsulate genomic RNA (gRNA), resulting in numerous viral progenies, which eventually exit the host cell, and spread infection to rest of the body. In this review, we primarily focus on genomic organization, structural and non-structural protein components, and potential prospective molecular targets for development of therapeutic drugs, convalescent plasm therapy, and a myriad of potential vaccines to tackle SARS-CoV-2 infection.


2013 ◽  
Vol 753-755 ◽  
pp. 1382-1385
Author(s):  
Xin Wang ◽  
Han Fu ◽  
Du Chen ◽  
Shu Mao Wang

Harvesting speed is a key factor that influences working quality, utilization and harvest efficiency of the working process of grain combine harvester. In order to solve multi-objective control and poor anti-interference ability of measurement system in combine harvester, this paper uses optimization theory and error analysis theory to integrate analyze multi-source disturbance of data which is acquired in measurement and control system. The optimum working state control algorithm which proposes by this paper has better robust and anti-interference features, and what is more, it can be targeted by low yield loss, high productivity and low power cost. It provides theoretical basis and data support for the domestic agricultural harvesting machine, which also is an effective means to heighten the automatic level of the agricultural information technology. Keywords: Grain Combine harvester; Multiple control strategy; Anti-interference ability


2012 ◽  
Vol 21 (1) ◽  
pp. 24-35 ◽  
Author(s):  
Ryoko Hidaka ◽  
Lynn Clark Callister

The purpose of our qualitative descriptive study was to describe the birth experiences of women using epidural analgesia for pain management. We interviewed nine primiparas who experienced vaginal births. Five themes emerged: (a) coping with pain, (b) finding epidural administration uneventful, (c) feeling relief having an epidural, (d) experiencing joy, and (e) having unsettled feelings of ambivalence. Although epidural analgesia was found to be effective for pain relief and may contribute to some women’s satisfaction with the birth experience, it does not guarantee a quality birth experience. In order to support and promote childbearing women’s decision making, we recommend improved education on the variety of available pain management options, including their risks and benefits. Fostering a sense of caring, connection, and control in women is a key factor to ensure positive birth experiences, regardless of pain management method.


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