Browse
Submit Data
Databases
API
Help

Dataset Information

8 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mutational Asymmetries in the SARS-CoV-2 Genome May Lead to Increased Hydrophobicity of Virus Proteins.

ABSTRACT: The genomic diversity of SARS-CoV-2 has been a focus during the ongoing COVID-19 pandemic. Here, we analyzed the distribution and character of emerging mutations in a data set comprising more than 95,000 virus genomes covering eight major SARS-CoV-2 lineages in the GISAID database, including genotypes arising during COVID-19 therapy. Globally, the C>U transitions and G>U transversions were the most represented mutations, accounting for the majority of single-nucleotide variations. Mutational spectra were not influenced by the time the virus had been circulating in its host or medical treatment. At the amino acid level, we observed about a 2-fold excess of substitutions in favor of hydrophobic amino acids over the reverse. However, most mutations constituting variants of interests of the S-protein (spike) lead to hydrophilic amino acids, counteracting the global trend. The C>U and G>U substitutions altered codons towards increased amino acid hydrophobicity values in more than 80% of cases. The bias is explained by the existing differences in the codon composition for amino acids bearing contrasting biochemical properties. Mutation asymmetries apparently influence the biochemical features of SARS CoV-2 proteins, which may impact protein-protein interactions, fusion of viral and cellular membranes, and virion assembly.

SUBMITTER: Matyasek R

PROVIDER: S-EPMC8227412 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Mutational analysis of structural proteins of SARS-CoV-2.

Project description:SARS-CoV-2 transmissibility is higher than that of other human coronaviruses; therefore, it poses a threat to the populated communities. We investigated mutations among envelope (E), membrane (M), and spike (S) proteins from different isolates of SARS-CoV-2 and plausible signaling influenced by mutated virus in a host. We procured updated protein sequences from the NCBI virus database. Mutations were analyzed in the retrieved sequences of the viral proteins through multiple sequence alignment. Additionally, the data was subjected to ScanPROSITE to analyse if the mutations generated a relevant sequence for host signaling. Unique mutations in E, M, and S proteins resulted in modification sites like PKC phosphorylation and N-myristoylation sites. Based on structural analysis, our study revealed that the D614G mutation in the S protein diminished the interaction with T859 and K854 of adjacent chains. Moreover, the S protein of SARS-CoV-2 consists of an Arg-Gly-Asp (RGD) tripeptide sequence, which could potentially interact with various members of integrin family receptors. RGD sequence in S protein might aid in the initial virus attachment. We speculated crucial host pathways which the mutated isolates of SARS-CoV-2 may alter like PKC, Src, and integrin mediated signaling pathways. PKC signaling is known to influence the caveosome/raft pathway which is critical for virus entry. Additionally, the myristoylated proteins might activate NF-κB, a master molecule of inflammation. Thus the mutations may contribute to the disease pathogenesis and distinct lung pathophysiological changes. Further the frequently occurring mutations in the protein can be studied for possible therapeutic interventions.

| S-EPMC7980187 | biostudies-literature

In Silico Study of Mutational Stability of SARS-CoV-2 Proteins.

Project description:Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), an enveloped RNA virus transmits by droplet infection thus affects the respiratory system. Different genomes have been reported globally for SARS-CoV-2 with moderate level of mutation which makes it harder to combat the virus. Mutational profiling and the relevant evolutionary aspect of coronavirus proteins namely spike glycoprotein, membrane protein, envelope protein, nucleoprotein, ORF1ab, ORF3a, ORF6, ORF7a, ORF7b and ORF8 were studied by in silico experiments. Clustering of the protein sequences and calculation of residue relative abundance were done to get an idea about the protein conservancy as well as finding out some representative sequences for phylogenetic and ancestral reconstruction. By mutational profiling and mutation analysis, the effect of mutations on the protein stability and their functional implication were studied. This study indicates the mutational effect on the proteins and their relevance in evolution, which directs us towards a better understanding of these variations and diversification of SARS-CoV-2 for useful future therapeutic study and thus aid in designing therapeutic agents keeping the highly variable regions in mind.

| S-EPMC8061876 | biostudies-literature

Opposing activities of IFITM proteins in SARS-CoV-2 infection

Project description:Interferon-induced transmembrane proteins (IFITMs) restrict infections by many viruses, but a subset of IFITMs enhance infections by specific coronaviruses through currently unknown mechanisms. We show that SARS-CoV-2 Spike-pseudotyped virus and genuine SARS-CoV-2 infections are generally restricted by human and mouse IFITM1, IFITM2, and IFITM3, using gain- and loss-of-function approaches. Mechanistically, SARS-CoV-2 restriction occurred independently of IFITM3 S-palmitoylation, indicating a restrictive capacity distinct from reported inhibition of other viruses. In contrast, the IFITM3 amphipathic helix and its amphipathic properties were required for virus restriction. Mutation of residues within the IFITM3 endocytosis-promoting Yxx? motif converted human IFITM3 into an enhancer of SARS-CoV-2 infection, and cell-to-cell fusion assays confirmed the ability of endocytic mutants to enhance Spike-mediated fusion with the plasma membrane. Overexpression of TMPRSS2, which increases plasma membrane fusion versus endosome fusion of SARS-CoV-2, attenuated IFITM3 restriction and converted amphipathic helix mutants into infection enhancers. In sum, we uncover new pro- and anti-viral mechanisms of IFITM3, with clear distinctions drawn between enhancement of viral infection at the plasma membrane and amphipathicity-based mechanisms used for endosomal SARS-CoV-2 restriction.

| S-SCDT-EMBOJ-2020-106501 | biostudies-other

Mutational hotspots and conserved domains of SARS-CoV-2 genome in African population.

Project description:BackgroundSince outbreak in December 2019, the highly infectious and pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over a million deaths globally. With increasing burden, the novel coronavirus has posed a dire threat to public health, social interaction, and global economy. Mutations in the SARS-CoV-2 genome are moderately evolving which might have contributed to its genome variability, transmission, replication efficiency, and virulence in different regions of the world.ResultsThe present study elucidated the mutational landscape in the SARS-CoV-2 genome among the African populace, which may have contributed to the virulence, spread, and pathogenicity observed in the region. A total of 3045 SARS-CoV-2 complete protein sequences with the reference viral sequence (EPI_ISL_402124) were mined and analyzed. SARS-CoV-2 ORF1ab, spike, ORF3, ORF8, and nucleocapsid proteins were observed as mutational hotspots in the African population and may be of keen interest in understanding the viral host relationship, while there is conservation in the ORF6, ORF7a, ORF7b, ORF10, envelope, and membrane proteins.ConclusionsThe accumulation of moderate mutations (though slowly), in the SARS-CoV-2 genome as seen in this present study, could be a promising strategy to develop antiviral drugs or vaccines. These antiviral interventions should target viral conserved domains and host cellular proteins and/or receptors involved in viral invasion and replication to avoid a new viral wave due to drug resistance and vaccine evasion.Supplementary informationThe online version contains supplementary material available at 10.1186/s43088-021-00102-1.

| S-EPMC7861160 | biostudies-literature

Structures from "Engineering Neutralizing SARS-CoV Antibodies to Bind SARS-CoV-2"

Project description: Not available

| S-BSST379 | biostudies-other

Increased sequence hydrophobicity reduces conformational specificity: A mutational case study of the Arc repressor protein.

Project description:The amino-acid sequences of soluble, globular proteins must have hydrophobic residues to form a stable core, but excess sequence hydrophobicity can lead to loss of native state conformational specificity and aggregation. Previous studies of polar-to-hydrophobic mutations in the β-sheet of the Arc repressor dimer showed that a single substitution at position 11 (N11L) leads to population of an alternate dimeric fold in which the β-sheet is replaced by helix. Two additional hydrophobic mutations at positions 9 and 13 (Q9V and R13V) lead to population of a differently folded octamer along with both dimeric folds. Here we conduct a comprehensive study of the sequence determinants of this progressive loss of fold specificity. We find that the alternate dimer-fold specifically results from the N11L substitution and is not promoted by other hydrophobic substitutions in the β-sheet. We also find that three highly hydrophobic substitutions at positions 9, 11, and 13 are necessary and sufficient for oligomer formation, but the oligomer size depends on the identity of the hydrophobic residue in question. The hydrophobic substitutions increase thermal stability, illustrating how increased hydrophobicity can increase folding stability even as it degrades conformational specificity. The oligomeric variants are predicted to be aggregation-prone but may be hindered from doing so by proline residues that flank the β-sheet region. Loss of conformational specificity due to increased hydrophobicity can manifest itself at any level of structure, depending upon the specific mutations and the context in which they occur.

| S-EPMC6322834 | biostudies-literature

The mutational dynamics of the SARS-CoV-2 virus in serial passages in vitro

Project description:Since its outbreak in 2019, Severe Acute Respiratory Syndrome Coronavirus 2 keeps surprising the medical community by evolving diverse immune escape mutations in a rapid and effective manner. To gain deeper insight into mutation frequency and dynamics, we isolated ten ancestral strains of SARS-CoV-2 and performed consecutive serial incubation in ten replications in a suitable and common cell line and subsequently analysed them using RT-qPCR and whole genome sequencing. Along those lines we hoped to gain fundamental insights into the evolutionary capacity of SARS-CoV-2 in vitro. Our results identified a series of adaptive genetic changes, ranging from unique convergent substitutional mutations and hitherto undescribed insertions. The region coding for spike proved to be a mutational hotspot, evolving a number of mutational changes including the already known substitutions at positions S:484 and S:501. We discuss the evolution of all specific adaptations as well as possible reasons for the seemingly inhomogeneous potential of SARS-CoV-2 in the adaptation to cell culture. The combination of serial passage in vitro with whole genome sequencing uncovers the immense mutational potential of some SARS-CoV-2 strains. The observed genetic changes of SARS-CoV-2 in vitro could not be explained solely by selectively neutral mutations but possibly resulted from the action of directional selection accumulating favourable genetic changes in the evolving variants, along the path of increasing potency of the strain. Competition among a high number of quasi-species in the SARS-CoV-2 in vitro population gene pool may reinforce directional selection and boost the speed of evolutionary change.

| S-EPMC8800542 | biostudies-literature

Cryo-EM structure of SARS-CoV-2 Spike Proteins on intact virions

Project description: Not available

| EMPIAR-10492 | biostudies-other

Mutational analysis and assessment of its impact on proteins of SARS-CoV-2 genomes from India.

Project description:Mutational status of SARS-CoV-2 genomes from India along with their impact on proteins was ascertained through multiple tools including MEGA, Genome Detective, SIFT, PROVEAN and ws-SNPs&GO. Excluding gaps and ambiguous sequences, 493 variable sites (152 parsimony informative and 341 singleton) were observed. NSP3 had the highest incidence of 101 sites followed by S protein (74), NSP12b (43) and ORF3a (31). Average mutations per sample for males and females was 2.56 and 2.88 respectively. Non-uniform geographical distribution of mutations suggests that sequences in some regions are mutating faster than others. There were 281 mutations (198 Neutral and 83 Disease) affecting amino acid sequence. NSP13 has a maximum of 14 Disease variants followed by S protein and ORF3a with 13 each. Disease mutations in genomes from asymptomatic people was mere 11% but those from deceased patients was at 38% indicating contribution of these mutations to the pathophysiology of the SARS-CoV-2.

| S-EPMC7860943 | biostudies-literature

Genomic chronicle of SARS-CoV-2: a mutational analysis with over 1 million genome sequences.

Project description:Use of information technologies to analyse big data on SARS-CoV-2 genome provides an insight for tracking variations and examining the evolution of the virus. Nevertheless, storing, processing, alignment and analyses of these numerous genomes are still a challenge. In this study, over 1 million SARS-CoV-2 genomes have been analysed to show distribution and relationship of variations that could enlighten development and evolution of the virus. In all genomes analysed in this study, a total of over 215M SNVs have been detected and average number of SNV per isolate was found to be 21.83. Single nucleotide variant (SNV) average is observed to reach 31.25 just in March 2021. The average variation number of isolates is increasing and compromising with total case numbers around the world. Remarkably, cytosine deamination, which is one of the most important biochemical processes in the evolutionary development of coronaviruses, accounts for 46% of all SNVs seen in SARS-CoV-2 genomes within 16 months. This study is one of the most comprehensive SARS-CoV-2 genomic analysis study in terms of number of genomes analysed in an academic publication so far, and reported results could be useful in monitoring the development of SARS-CoV-2.

| S-EPMC8573839 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data