scholarly journals Evolution of SARS-CoV-2 Envelope, Membrane, Nucleocapsid, and Spike Structural Proteins from the Beginning of the Pandemic to September 2020: A Global and Regional Approach by Epidemiological Week

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 243
Author(s):  
Paloma Troyano-Hernáez ◽  
Roberto Reinosa ◽  
África Holguín

Monitoring acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic diversity and emerging mutations in this ongoing pandemic is crucial for understanding its evolution and assuring the performance of diagnostic tests, vaccines, and therapies against coronavirus disease (COVID-19). This study reports on the amino acid (aa) conservation degree and the global and regional temporal evolution by epidemiological week for each residue of the following four structural SARS-CoV-2 proteins: spike, envelope, membrane, and nucleocapsid. All, 105,276 worldwide SARS-CoV-2 complete and partial sequences from 117 countries available in the Global Initiative on Sharing All Influenza Data (GISAID) from 29 December 2019 to 12 September 2020 were downloaded and processed using an in-house bioinformatics tool. Despite the extremely high conservation of SARS-CoV-2 structural proteins (>99%), all presented aa changes, i.e., 142 aa changes in 65 of the 75 envelope aa, 291 aa changes in 165 of the 222 membrane aa, 890 aa changes in 359 of the 419 nucleocapsid aa, and 2671 changes in 1132 of the 1273 spike aa. Mutations evolution differed across geographic regions and epidemiological weeks (epiweeks). The most prevalent aa changes were D614G (81.5%) in the spike protein, followed by the R203K and G204R combination (37%) in the nucleocapsid protein. The presented data provide insight into the genetic variability of SARS-CoV-2 structural proteins during the pandemic and highlights local and worldwide emerging aa changes of interest for further SARS-CoV-2 structural and functional analysis.

2021 ◽  
Author(s):  
Dave Constable ◽  
Licia Ray ◽  
Sarah Badman ◽  
Chris Arridge ◽  
Chris Lorch ◽  
...  

<p>Since arriving at Jupiter, Juno has observed instances of field-aligned proton and electron beams, in both the upward and downward current regions. These field-aligned beams are identified by inverted-V structures in plasma data, which indicate the presence of potential structures aligned with the magnetic field. The direction, magnitude and location of these potential structures is important, as it affects the characteristics of any resultant field-aligned current. At high latitudes, Juno has observed potentials of 100’s of kV occurring in both directions. Charged particles that are accelerated into Jupiter’s atmosphere and precipitate can excite aurora; likewise, particles accelerated away from the planet can contribute to the population of the magnetosphere.</p> <p>Using a time-varying 1-D spatial, 2-D velocity space Vlasov code, we examine magnetic field lines which extend from Jupiter into the middle magnetosphere. By applying and varying a potential difference at the ionosphere, we can gain insight into the effect these have on the plasma population, the potential structure, and plasma densities along the field line. Utilising a non-uniform mesh, additional resolution is applied in regions where particle acceleration occurs, allowing the spatial and temporal evolution of the plasma to be examined. Here, we present new results from our model, constrained, and compared with recent Juno observations, and examining both the upward and downward current regions.</p>


2015 ◽  
Vol 11 (A29B) ◽  
pp. 472-472
Author(s):  
Jeffrey M. Silverman ◽  
Stephanie Pickett ◽  
J. Craig Wheeler ◽  
Alexei V. Filippenko

We are analysing late-time (older than about 150 d past explosion) optical spectra of Type II-Plateau (IIP) supernovae (SNe), which are H-rich SNe that come from red supergiant (RSG) progenitors. The dataset includes nearly 100 spectra of about 40 objects, making this the largest sample of SN IIP nebular spectra ever investigated. Quantitative criteria from within the spectra themselves are employed to determine if an observation is truly nebular, and thus should be included in the study. We present the temporal evolution of the fluxes, shapes, and velocities of various emission lines (see, for example, Fig. 1). These measured values are also compared to photometric data in order to search for correlations that can allow us to gain insight into the diversity of RSG progenitors and learn more about the details of the explosion itself.


2019 ◽  
Vol 33 (1) ◽  
Author(s):  
Fariba M. Donovan ◽  
Lisa Shubitz ◽  
Daniel Powell ◽  
Marc Orbach ◽  
Jeffrey Frelinger ◽  
...  

SUMMARY Since its description nearly 130 years ago, hundreds of studies have deepened our understanding of coccidioidomycosis, also known as valley fever (VF), and provided useful diagnostic tests and treatments for the disease caused by the dimorphic fungi Coccidioides spp. In general, most of the literature has addressed well-established infections and has described patients who have experienced major complications. In contrast, little attention has been given to the earliest consequences of the pathogen-host interaction and its implications for disease manifestation, progression, and resolution. The purpose of this review is to highlight published studies on early coccidioidomycosis, identify gaps in our knowledge, and suggest new or former research areas that might be or remain fertile ground for insight into the early stages of this invasive fungal disease.


2021 ◽  
Vol 8 ◽  
Author(s):  
Sonia Beeckmans ◽  
Edilbert Van Driessche

Since early 2020, the world suffers from a new beta-coronavirus, called SARS-CoV-2, that has devastating effects globally due to its associated disease, Covid-19. Until today, Covid-19, which not only causes life-threatening lung infections but also impairs various other organs and tissues, has killed hundreds of thousands of people and caused irreparable damage to many others. Since the very onset of the pandemic, huge efforts were made worldwide to fully understand this virus and numerous studies were, and still are, published. Many of these deal with structural analyses of the viral spike glycoprotein and with vaccine development, antibodies and antiviral molecules or immunomodulators that are assumed to become essential tools in the struggle against the virus. This paper summarizes knowledge on the properties of the four structural proteins (spike protein S, membrane protein M, envelope protein E and nucleocapsid protein N) of the SARS-CoV-2 virus and its relatives, SARS-CoV and MERS-CoV, that emerged few years earlier. Moreover, attention is paid to ways to analyze such proteins using freely available bioinformatic tools and, more importantly, to bring these proteins alive by looking at them on a computer/laptop screen with the easy-to-use but highly performant and interactive molecular graphics program DeepView. It is hoped that this paper will stimulate non-bioinformaticians and non-specialists in structural biology to scrutinize these and other macromolecules and as such will contribute to establishing procedures to fight these and maybe other forthcoming viruses.


Author(s):  
Farwa Mukhtar ◽  
Muhammad Tahir khan ◽  
Arif Malik ◽  
Shaoliang Peng ◽  
Doaa Darwish ◽  
...  

The structural proteins, spike (S), nucleocapsid (N), membrane (M), and envelope (E), of severe acute respiratory syndrome (SARS-CoV-2) play a critical role from attachment to replication and virulency. Recently a bulk of genomes have been sequenced from different geographical regions with significant number of variations. Therefore, the current study was aimed to find variations in the structural proteins. This is the first comprehensive study in which we screened 2,95,000 complete genomes in global initiative on sharing all influenza data (GISAID), submitted from December 2019 to December 2020. We detected 4725 non-synonymous mutations in S, 627 in M, 259 in E, and 1631 mutations in N protein, among which the most frequently occurring mutations in S protein are D614G (n=2,66,513), A222V (n=59,697), L18F (n=28,015) and that of M protein are; T175M (n=1286), D3G (n=968), L17I (n=621), A2V (n=463), and A2S (n=460). The most commonly circulating variants in E includes, S68F (n=419), P71S (n=264), and L73F (n=218). Similarly, the N protein also harbored the most common variants which include; R203K (n=82,570), G204R (n=81,858), and A220V (n=39,729). The frequency of N501Y (n=4362) in S is determining a tight interaction of CoV-2 RBD with ACE2. These wide range of mutations in structural proteins may not only affect the therapeutic efforts but also the vaccines efficacy and diagnostics specificity. We suggest that geographically strain specific variations should be investigated for effective drugs, vaccine, and the antibodies combinations. Alternatively, immune boosting compounds might be very useful for successful eradication of CoV-2 infections.


2021 ◽  
Author(s):  
Grant A Kay ◽  
Sophie I Owen ◽  
Emanuele Giorgi ◽  
Christopher T Williams ◽  
Stefanie Menzies ◽  
...  

Abstract Severe acute respiratory coronavirus 2 (SARS-CoV-2) has spread globally since its emergence in 2019. Most SARS-CoV-2 infections generate immune responses leading to rising levels of immunoglobulins (Ig) M, A and G which can be detected using diagnostic tests including enzyme-linked immunosorbent assays (ELISA). Whilst implying previous SARS-CoV-2 infection, the detection of Ig by ELISA does not guarantee the presence of neutralising antibodies (NAb) that can prevent the virus infecting cells. Plaque reduction neutralisation tests (PRNT) detect NAb but are not amenable to mass testing as they take several days and require use of viable SARS-CoV-2 in high biocontainment laboratories. We evaluated the ability of IgG and IgM ELISAs targeting SARS-CoV-2 spike subunit 1 (S1) and nucleocapsid protein (NP) at predicting the presence and magnitude of NAb determined by PRNT. SARS-CoV-2 IgG ELISA correlated well with NAb and was highly sensitive (93.8% [95% CI 79.2–99.2]) and specific (88.9% [95% CI 51.8–99.7%]) at predicting the presence of NAb. There was not a strong correlation between IgM ELISA and PRNT result. IgG ELISA provides a useful, high throughput method of predicting the presence of neutralising antibodies, with higher ELISA results increasing the likelihood of having a greater NAb titre.


2021 ◽  
Author(s):  
Aneta Tarczewska ◽  
Marta Kolonko-Adamska ◽  
Mirosław Zarębski ◽  
Jerzy W Dobrucki ◽  
Andrzej Ożyhar ◽  
...  

One of the main structural proteins of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the nucleocapsid protein (N). The basic function of this protein is to bind genomic RNA and to form a protective nucleocapsid in the mature virion. The intrinsic ability of the N protein to interact with nucleic acids makes its purification very challenging. Therefore, typically employed purification methods appear to be insufficient for removing nucleic acid contamination. In this study, we present a novel purification protocol that enables the N protein to be prepared without any bound nucleic acids. We also performed comparative structural analysis of the N protein contaminated with nucleic acids and free of contamination and showed significant differences in the structural and phase separation properties of the protein. These results indicate that nucleic-acid contamination may severely affect molecular properties of the purified N protein. In addition, the notable ability of the N protein to form condensates whose morphology and behaviour suggest more ordered forms resembling gel-like or solid structures is described.


2020 ◽  
Author(s):  
David Cate ◽  
Helen Hsieh ◽  
Veronika Glukhova ◽  
Joshua D Bishop ◽  
H Gleda Hermansky ◽  
...  

<p>The global COVID-19 pandemic has created an urgent demand for accurate rapid point of care diagnostic tests. Antigen-based assays are suitably inexpensive and can be rapidly mass-produced, but sufficiently accurate performance requires highly-optimized antibodies and assay conditions. An automated liquid handling system, customized to handle lateral flow immunoassay (LFA) arrays, was used for high-throughput antibody screening of anti-nucleocapsid antibodies that will perform optimally on an LFA. Six hundred seventy-three anti-nucleocapsid antibody pairs were tested as both capture and detection reagents with the goal of finding those pairs that have the greatest affinity for unique epitopes of the nucleocapsid protein of SARS-CoV-2 while also performing optimally in an LFA format. In contrast to traditional antibody screening methods (e.g. ELISA, bio-layer interferometry), the methods described here integrate real-time LFA reaction kinetics and binding directly on nitrocellulose. We have identified several candidate antibody pairs that are suitable for further development of an LFA for SARS-CoV-2. </p>


Author(s):  
Daniel Berman

Antimicrobial resistance (AMR) is one of the most serious clinical and public healthcare challenges. In this video Daniel Berman,  Nesta Challenges, provides an overview of the Longitude Prize, why the prize was set up and what the prize hopes to achieve. Daniel also provides insight into some of the rapid diagnostic tests currently in the running for the £8 million prize.


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