scholarly journals Evidence for the dependence of the SARS-Cov-2 Delta high diffusivity on the associated N:G215C nucleocapsid mutation

2021 ◽  
Author(s):  
Vito Marchitelli ◽  
Claudia Troise ◽  
Antonio Parisi ◽  
Angelica Bianco ◽  
Laura Del Sambro ◽  
...  
Keyword(s):  
Amino Acid ◽  
Genome Sequencing ◽  
Virus Genome ◽  
Relative Increase ◽  
Amino Acid Sequences ◽  
Spike Protein ◽  
The United Kingdom ◽  
New Variant ◽  
Adaptive Effect ◽  
Selective Environment

Abstract The continuous evolution of the SARS-CoV-2 virus genome and the consequent substitutions observed in the amino acid sequences, can induce significant changes in parameters such as diffusivity and pathogenicity, and causes constant concern regarding the efficacy of vaccines against the new variants in circulation. In recent months there has been an increase in the number of infections first in India, and more recently in the United Kingdom. The genome sequencing of the samples showed that this increase coincided with the emergence of a new variant, B.1.617.2, also known as VOC Delta. This variant is rapidly becoming dominant in several countries, causing increasing concern for its extreme diffusivity and its ability to often overcome the vaccines. The high diffusivity of this variant is normally ascribed to the Spike protein mutations. However, we will show here that it is rather due to the nucleocapsid substitution N:G215C. This is made clear by comparing, in the genomic sequences available on the GISAID database, the relative increase of the Delta variant with and without the associated N:G215C substitution. Once the extreme diffusivity of the Delta variant with associated nucleocapsid aminoacidic substitution is evidenced, we tentatively explain it as possibly due to the adaptive effect of the highly selective environment in Countries with high levels of vaccination.

Sars-Cov-2 Spike protein function prediction using a convolutional neural network ensemble

2021 ◽  
pp. 7831-7845
Author(s):  
Raghad Monther Eid, Eman K. Elsayed, Fatma T. Ghanam
Keyword(s):  
Neural Network ◽  
Amino Acid ◽  
Protein Function ◽  
Protein Function Prediction ◽  
Small Error ◽  
Amino Acid Sequences ◽  
Spike Protein ◽  
Neural Network Ensemble ◽  
Classification Problems ◽  
Past Experiences

Introduction: SARS-CoV-2 has become a worldwide pandemic that affects all aspects of life; therefore, numerous organizations and open exploration foundations focus their efforts on research for viable therapeutics. Given past experiences and involvement in SARS, the essential focus has been the Spike protein, considered as the perfect objective for COVID-19 immunotherapies. Most of the vaccines being developed target the spike proteins because this protein covers the virus and helps it invade human cells. Methods: Applications of deep neural network is a quickly expanding field now reaching many areas including proteomics. Results: To be precise, convolutional neural networks have been used for identifying the functional role of amino acid sequences, because of its ability to give nearly accurate results for multi-label classification problems. Here we present a modified convolutional deep learning model that can  identify if a given amino acid sequence is a spike protein or not based on the length of the sequence and the function of the protein, that will be done  with a short execution time and a relatively small error rate. Conclusion: CNN is an efficient tool at supervised multilabel classification problems

scholarly journals Insights into the Selective Pressures Restricting Pelargonium Flower Break Virus Genome Variability: Evidence for Host Adaptation

2006 ◽  
Vol 80 (16) ◽  
pp. 8124-8132 ◽  
Author(s):  
Patricia Rico ◽  
Pilar Ivars ◽  
Santiago F. Elena ◽  
Carmen Hernández
Keyword(s):  
Amino Acid ◽  
Leucine Zipper ◽  
Critical Role ◽  
Chenopodium Quinoa ◽  
Virus Genome ◽  
Acid Sites ◽  
Genomic Region ◽  
Amino Acid Sequences ◽  
Nucleotide Substitutions ◽  
Selective Pressures

ABSTRACT The molecular diversity of Pelargonium flower break virus (PFBV) was assessed using a collection of isolates from different geographical origins, hosts, and collecting times. The genomic region examined was 1,828 nucleotides (nt) long and comprised the coding sequences for the movement (p7 and p12) and the coat (CP) proteins, as well as flanking segments including the entire 3′ untranslated region (3′ UTR). Some constraints limiting viral heterogeneity could be inferred from sequence analyses, such as the conservation of the amino acid sequences of p7 and of the shell domain of the CP, the maintenance of a leucine zipper motif in p12, and the preservation of a particular folding in the 3′ UTR. A remarkable covariation, involving five specific amino acid sites, was found in the CP of isolates largely propagated in the local lesion host Chenopodium quinoa and in the progeny of a PFBV variant subjected to serial passages in this host. Concomitant with this covariation, up to 30 nucleotide substitutions in a 1,428-nt region of the viral RNA could be attributable to C. quinoa-specific adaptation, representing one of the most outstanding cases of host-driven genome variation for a plant virus. Globally, the results indicate that the selective pressures exerted by the host play a critical role in shaping PFBV populations and that these populations are likely being selected for at both protein and RNA levels.

scholarly journals Structural analysis of the Spike of the Omicron SARS-COV-2 variant by Cryo-EM and implications for immune evasion

2021 ◽  
Author(s):  
Dongchun Ni ◽  
Kelvin Lau ◽  
Priscilla Turelli ◽  
Charlene Raclot ◽  
Bertrand Beckert ◽  
...  
Keyword(s):  
South Africa ◽  
United Kingdom ◽  
Structural Analysis ◽  
High Resolution ◽  
Immune Evasion ◽  
Spike Protein ◽  
Spike Glycoprotein ◽  
The United Kingdom ◽  
New Variant ◽  
Structural Insights

The Omicron (B.1.1.529) SARS-COV-2 was reported on November 24, 2021 and declared a variant of concern a couple of days later. With its constellation of mutations acquired by this variant on its Spike glycoprotein and the speed at which this new variant has replaced the previously dominant variant Delta in South Africa and the United Kingdom, it is crucial to have atomic structural insights to reveal the mechanism of its rapid proliferation. Here we present a high-resolution cryo-EM structure of the Spike protein of the Omicron variant.

scholarly journals Genetic Determinants of Sindbis Virus Mosquito Infection Are Associated with a Highly Conserved Alphavirus and Flavivirus Envelope Sequence

2007 ◽  
Vol 82 (6) ◽  
pp. 2966-2974 ◽  
Author(s):  
Dennis J. Pierro ◽  
Erik L. Powers ◽  
Ken E. Olson
Keyword(s):  
Amino Acid ◽  
Sindbis Virus ◽  
Virus Genome ◽  
Growth Patterns ◽  
Amino Acid Sequences ◽  
Genetic Determinants ◽  
Nucleotide Substitutions ◽  
Conserved Sequence ◽  
E2 Glycoprotein ◽  
Envelope Sequence

ABSTRACT Wild-type Sindbis virus (SINV) strain MRE16 efficiently infects Aedes aegypti midgut epithelial cells (MEC), but laboratory-derived neurovirulent SINV strain TE/5′2J infects MEC poorly. SINV determinants for MEC infection have been localized to the E2 glycoprotein. The E2 amino acid sequences of MRE16 and TE/5′2J differ at 60 residue sites. To identify the genetic determinants of MEC infection of MRE16, the TE/5′2J virus genome was altered to contain either domain chimeras or more focused nucleotide substitutions of MRE16. The growth patterns of derived viruses in cell culture were determined, as were the midgut infection rates (MIR) in A. aegypti mosquitoes. The results showed that substitutions of MRE16 E2 aa 95 to 96 and 116 to 119 into the TE/5′2J virus increased MIR both independently and in combination with each other. In addition, a unique PPF/.GDS amino acid motif was located between these two sites that was found to be a highly conserved sequence among alphaviruses and flaviviruses but not other arboviruses.

scholarly journals Genetic characterization of a novel Tib-derived variant of soybean Kunitz trypsin inhibitor detected in wild soybean (Glycine soja)

Genome ◽  
2004 ◽  
Vol 47 (1) ◽  
pp. 9-14 ◽  
Author(s):  
Ke-Jing Wang ◽  
Tetsuro Yamashita ◽  
Masao Watanabe ◽  
Yoshihito Takahata
Keyword(s):  
Amino Acid ◽  
Trypsin Inhibitor ◽  
Glycine Soja ◽  
Polyacrylamide Gel Electrophoresis ◽  
Wild Soybean ◽  
Amino Acid Sequences ◽  
Kunitz Trypsin Inhibitor ◽  
Variant Type ◽  
New Variant ◽  
Novel Variant

A novel variant of soybean Kunitz trypsin inhibitor (SKTI) was detected in 530 lines of wild soybean (Glycine soja). This variant showed an intermediate electrophoretic mobility between the Tia and Tic types. In isoelectric focusing polyacrylamide gel electrophoresis gels containing urea, this variant had a similar isoelectric point as that of Tia. The genetic analysis of SKTI bands in F2 seeds from crosses of the new variant type with Tia or Tic type showed that this variant type is controlled by a codominant allele at the SKTI locus. We propose the genetic symbol Tif for this novel variant. When the nucleotide sequence of the Tif gene was compared with those of other types of SKTI genes (Tia, Tib, and Tic), the sequence of Tif was identical to that of Tib with the exception of one A[Formula: see text]G transitional mutation occurring at position 676 of Tif. This mutation resulted in an amino acid change from Lys to Glu at the 178 residue. These results suggest that this variant is derived from Tib through a point mutation. In addition, we settled an inconsistency in the number of amino acid differences between Tia and Tib (eight or nine). Analysis of nucleotide and amino acid sequences revealed that Tib was different from Tia by nine amino acids.Key words: soybean Kunitz trypsin inhibitor, polymorphism, gene sequence, soybean, wild soybean.

scholarly journals Analysis of the ARTIC version 3 and version 4 SARS-CoV-2 primers and their impact on the detection of the G142D amino acid substitution in the spike protein

2021 ◽  
Author(s):  
James Davis ◽  
Scott Wesley Long ◽  
Paul Christensen ◽  
Randall J Olsen ◽  
Robert Olson ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitution ◽  
Drop Out ◽  
Spike Protein ◽  
Clinical Samples ◽  
New Variant ◽  
Common Resource ◽  
Improved Performance ◽  
Primer Sets ◽  
Public Repositories

The ARTIC Network provides a common resource of PCR primer sequences and recommendations for amplifying SARS-CoV-2 genomes. The initial tiling strategy was developed with the reference genome Wuhan-01, and subsequent iterations have addressed areas of low amplification and sequence drop out. Recently, a new version (V4) was released, based on new variant genome sequences, in response to the realization that some V3 primers were located in regions with key mutations. Herein, we compare the performance of the ARTIC V3 and V4 primer sets with a matched set of 663 SARS-CoV-2 clinical samples sequenced with an Illumina NovaSeq 6000 instrument. We observe general improvements in sequencing depth and quality, and improved resolution of the SNP causing the D950N variation in the spike protein. Importantly, we also find nearly universal presence of spike protein substitution G142D in Delta-lineage samples. Due to the prior release and widespread use of the ARTIC V3 primers during the initial surge of the Delta variant, it is likely that the G142D amino acid substitution is substantially underrepresented among early Delta variant genomes deposited in public repositories. In addition to the improved performance of the ARTIC V4 primer set, this study also illustrates the importance of the primer scheme in downstream analyses.

scholarly journals Evolution of the hepatitis E virus hypervariable region

2012 ◽  
Vol 93 (11) ◽  
pp. 2408-2418 ◽  
Author(s):  
Donald B. Smith ◽  
Jeff Vanek ◽  
Sandeep Ramalingam ◽  
Ingolfur Johannessen ◽  
Kate Templeton ◽  
...  
Keyword(s):  
Amino Acid ◽  
Positive Selection ◽  
Hepatitis E Virus ◽  
Hypervariable Region ◽  
Hepatitis E ◽  
Virus Genome ◽  
Amino Acid Sequences ◽  
Specific Sequence ◽  
Virus Genotypes ◽  
Selection For

The presence of a hypervariable (HVR) region within the genome of hepatitis E virus (HEV) remains unexplained. Previous studies have described the HVR as a proline-rich spacer between flanking functional domains of the ORF1 polyprotein. Others have proposed that the region has no function, that it reflects a hypermutable region of the virus genome, that it is derived from the insertion and evolution of host sequences or that it is subject to positive selection. This study attempts to differentiate between these explanations by documenting the evolutionary processes occurring within the HVR. We have measured the diversity of HVR sequences within acutely infected individuals or amongst sequences derived from epidemiologically linked samples and, surprisingly, find relative homogeneity amongst these datasets. We found no evidence of positive selection for amino acid substitution in the HVR. Through an analysis of published sequences, we conclude that the range of HVR diversity observed within virus genotypes can be explained by the accumulation of substitutions and, to a much lesser extent, through deletions or duplications of this region. All published HVR amino acid sequences display a relative overabundance of proline and serine residues that cannot be explained by a local bias towards cytosine in this part of the genome. Although all published HVRs contain one or more SH3-binding PxxP motifs, this motif does not occur more frequently than would be expected from the proportion of proline residues in these sequences. Taken together, these observations are consistent with the hypothesis that the HVR has a structural role that is dependent upon length and amino acid composition, rather than a specific sequence.

scholarly journals Suboptimal Nucleotides in the Infectious, Pathogenic Simian Immunodeficiency Virus Clone SIVmac239

2001 ◽  
Vol 75 (8) ◽  
pp. 4019-4022 ◽  
Author(s):  
Louis Alexander ◽  
Lynn Denekamp ◽  
Susan Czajak ◽  
Ronald C. Desrosiers
Keyword(s):  
Amino Acid ◽  
Simian Immunodeficiency Virus ◽  
High Viral Load ◽  
Virus Genome ◽  
Amino Acid Sequences ◽  
Primer Binding Site ◽  
Nucleotide Change ◽  
Single Nucleotide ◽  
Single Nucleotide Change ◽  
Immunodeficiency Virus

ABSTRACT We analyzed virus sequences in two monkeys infected with SIVmac239 and two monkeys infected with SHIVnef that maintained high, persisting viral loads. Sequence changes were observed consistently at four loci in all four animals: a single nucleotide change in the Lys-tRNA primer binding site in the 5′ long terminal repeat; two nucleotide changes that resulted in two amino acid changes in thepol gene product; and a single nucleotide change in the region of the simian immunodeficiency virus genome where therev and env genes overlap, resulting in changes in the predicted amino acid sequences of both gene products. None of these mutations were seen in short-term cultures of CEM×174 cells infected with SIVmac239 or SHIVnef. At all four positions in all four animals, the new sequences represented consensus sequences for primate lentiviruses, whereas the inoculum sequences at these four loci have either never been or rarely been reported outside of SIVmac239. Thus, although cloned SIVmac239 is consistently pathogenic and consistently induces high viral load set points, it is clearly less than optimal at these four nucleotide positions.

scholarly journals The lethal triad: SARS-CoV-2 Spike, ACE2 and TMPRSS2. Mutations in host and pathogen may affect the course of pandemic

2021 ◽  
Author(s):  
Matteo Calcagnile ◽  
Patricia Forgez ◽  
Marco Alifano ◽  
Pietro Alifano
Keyword(s):  
Amino Acid ◽  
Receptor Binding ◽  
Virus Transmission ◽  
Threat Assessment ◽  
Spike Protein ◽  
Binding Motif ◽  
Lethal Triad ◽  
New Variant ◽  
South East England ◽  
And Control

AbstractVariants of SARS-CoV-2 have been identified rapidly after the beginning of pandemic. One of them, involving the spike protein and called D614G, represents a substantial percentage of currently isolated strains. While research on this variant was ongoing worldwide, on December 20th 2020 the European Centre for Disease Prevention and Control reported a Threat Assessment Brief describing the emergence of a new variant of SARS-CoV-2, named B.1.1.7, harboring multiple mutations mostly affecting the Spike protein. This viral variant has been recently associated with a rapid increase in COVID-19 cases in South East England, with alarming implications for future virus transmission rates. Specifically, of the nine amino acid replacements that characterize the Spike in the emerging variant, four are found in the region between the Fusion Peptide and the RBD domain (namely the already known D614G, together with A570D, P681H, T716I), and one, N501Y, is found in the Spike Receptor Binding Domain – Receptor Binding Motif (RBD-RBM). In this study, by using in silico biology, we provide evidence that these amino acid replacements have dramatic effects on the interactions between SARS-CoV-2 Spike and the host ACE2 receptor or TMPRSS2, the protease that induces the fusogenic activity of Spike. Mostly, we show that these effects are strongly dependent on ACE2 and TMPRSS2 polymorphism, suggesting that dynamics of pandemics are strongly influenced not only by virus variation but also by host genetic background.

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