scholarly journals Non-synonymous Mutations of SARS-Cov-2 Leads Epitope Loss and Segregates its Varaints

2020 ◽  
Author(s):  
Aayatti Mallick Gupta ◽  
Sukhendu Mandal
Keyword(s):  
Amino Acid ◽  
Important Determinant ◽  
Surface Glycoprotein ◽  
Spike Glycoprotein ◽  
Synonymous Mutations ◽  
The World

Abstract The non-synonymous mutations of SARS-Cov-2 isolated from across the world have been identified during the last few months. The surface glycoprotein spike of SARS-Cov-2 forms the most important hotspot for amino acid alterations followed by the ORF1a/ORF1ab poly-proteins. It is evident that the D614G mutation in spike glycoprotein and P4715L in RdRp is the important determinant of SARS-Cov-2 evolution since its emergence. P4715L in RdRp, G251V in ORF3a and S1498F of Nsp3 is associated with the epitope loss that may influence pathogenesis caused by antibody escape variants. Phylogenomics distinguished the ancestral viral samples from China and most part of Asia, isolated between Dec, 2019 to Feb, 2020 and the evolved variants isolated from Europe and Americas from Mar, 2020 to April, 2020. The evolved variants have been found to predominant globally with the loss of epitopes from its proteins. These have implications for SARS-Cov-2 transmission, pathogenesis and immune interventions.

scholarly journals Loss of Epitopes from SARS-Cov-2 Proteins for Non-synonymous Mutations: A Potential Global Threat

2020 ◽  
Author(s):  
Aayatti Mallick Gupta ◽  
Sukhendu Mandal
Keyword(s):  
Amino Acid ◽  
Positive Selection ◽  
Important Determinant ◽  
Surface Glycoprotein ◽  
Spike Glycoprotein ◽  
North Central ◽  
Synonymous Mutations ◽  
Indian Isolates ◽  
Global Threat ◽  
Selection Of

The non-synonymous mutations of SARS-Cov-2 have been identified, isolated, and sequenced across several COVID-19 infected countries from Asia, Africa, Europe, North, Central, and South Americas, and Oceania during the last few months since its emergence in Dec 2019 to April 2020. The surface glycoprotein spike of SARS-Cov-2 forms the most important hotspot for amino acid alterations followed by the ORF1a/ORF1ab poly-proteins. It is evident that the D614G mutation in spike glycoprotein and P4715L in RdRp showed co-existence among the various samples and are the important determinant of SARS-Cov-2 evolution from its emergence in China to the present epicenter. Both these mutations are increasing in number from March 2020 to become the most dominant subtype of SARS-Cov-2. It is important to notice that mutation P4715L in RdRp, G251V in ORF3a, and S1498F in the PL2 domain of NSP3 is associated with the epitope loss that may influence pathogenesis caused by antibody escape variants. Phylogenomics showed two distinct clades, (i) green clade with ancestral viral samples from China and most of Asia isolated between Dec 2019 to Feb 2020, and (ii) red with the evolved variants isolated from Europe and Americas from Mar 2020 to April 2020. The evolved variants have been found to show the loss in epitopes from its different proteins. SARS-Cov-2 from the Indian isolates distributed under both clades. The positive selection of mutations among the red clade is becoming predominant globally. These findings have important implications for SARS-Cov-2 transmission, pathogenesis, and immune interventions.

scholarly journals Genomic surveillance reveals the emergence of SARS-CoV-2 Lineage A from Islamabad Pakistan

2021 ◽  
Author(s):  
Massab Umair ◽  
Aamer Ikram ◽  
Zaira Rehman ◽  
Syed Adnan Haider ◽  
Nazish Badar ◽  
...  
Keyword(s):  
Amino Acid ◽  
Virus Replication ◽  
Cleavage Site ◽  
Disease Dynamics ◽  
Amino Acid Deletion ◽  
Spike Glycoprotein ◽  
Furin Cleavage ◽  
Actual Impact ◽  
Furin Cleavage Site ◽  
The World

The lineage A of SARS-CoV-2 has been around the world since the start of the pandemic. In Pakistan the last case of lineage A was reported in April, 2021 since then no case has been reported. In November, 2021 during routine genomic surveillance at National Institute of Health we have found 07 cases of lineage A from Islamabad, Pakistan. The study reports two novel deletions in the spike glycoprotein. One 09 amino acid deletion (68-76 a.a) is found in the S1 subunit while another 10 amino acid deletion (679-688 a.a) observed at the junction of S1/S2 referred as furin cleavage site. The removal of furin cleavage site may result in impaired virus replication thus decreasing its pathogenesis. The actual impact of these two deletions on the virus replication and disease dynamics needs to be studied in detail. Moreover, the enhanced genomic surveillance will be required to track the spread of this lineage in other parts of the country.

scholarly journals Spike protein modeling and single amino acid variant analysis might suggest reduced transmitability of SARS-CoV-2 in Jordan, Middle East

2020 ◽  
Author(s):  
Walid Al-Zyoud ◽  
Hazem Haddad
Keyword(s):  
Crystal Structure ◽  
Amino Acid ◽  
Middle East ◽  
Active Sites ◽  
Trna Synthetase ◽  
Surface Glycoprotein ◽  
Spike Protein ◽  
Single Amino Acid ◽  
Spike Glycoprotein ◽  
Amino Acid Variants

Abstract Spike protein (approx. 180 kDa) is the surface glycoprotein of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) necessary for the interaction of the virus with human endothelial cell receptors on the cell membrane to be engulfed causing COVID-19 disease after binding with the angiotensin-converting enzyme 2 (ACE2) with an evident activation by type II transmembrane protease TMPRSS2 . Therefore, mutations and amino acid variants analysis are essential in characterizing the mechanism of binding of spike protein with its receptor, which totally gives insights on possibilities to design a peptide or nucleotide-based vaccine for COVID-19. Here, we employed Iterative Threading Assembly Refinement (I-TASSER) and Multiple Alignment using Fast Fourier Transform (MAFFT) to predict the three-dimensional structure and to analyze the amino acid variants for spike protein sequences of SARS-CoV-2 from GISAID database of samples collected from Jordan to try to find a justification for low number of confirmed COVID-19 in Jordan, Middle East. Our findings showed the molecules structurally close to the spike glycoprotein from the Enzyme Commission (EC) numbers and active sites included Isoleucyl-tRNA synthetase, Crystal structure of the tricorn protease (hydrolase); Crystal structure of the T. Thermophilus RNA polymerase holoenzyme (transferase); Crystal structure of the complex between pyruvate-ferredoxin oxidoreductase from Desulfovibrio africanus and pyruvate (oxidoreductase); and Reovirus core (virus). Our MAFFT findings showed that Four Amino Acid Variants (SAV) founded in 20 samples of SARS-CoV-2 were not conserved residues in spike glycoprotein. What is equal to 5% of samples showed tyrosine (polar) deletion at Y144 , 62% of samples showed aspartate (polar, acidic) substitution to glycine (nonpolar) at D614G, 5% of samples showed aspartate (polar, acidic) substitution to tyrosine (polar) at D1139Y and 5% of samples showed glycine (nonpolar) substitution to serine (polar) at G1167S respectively. By using Phyre2, our findings have shown lower sensitive mutational that cannot affect the pocket region or alpha and beta-sheet in all mutations except for D614G, which has the highest mutational sensitivity score (5 out of 9) indicating a bigger effect on the function of spike protein. This might suggest, in general, a reduced transmitability of SARS-CoV-2 in Jordan, Middle East. As the crystal structure of spike protein is not revealed yet, it was not possible to compare the predicted modes versus each other.

scholarly journals The Functional Consequences of the Novel Ribosomal Pausing Site in SARS-CoV-2 Spike Glycoprotein RNA

2021 ◽  
Vol 22 (12) ◽  
pp. 6490
Author(s):  
Olga A. Postnikova ◽  
Sheetal Uppal ◽  
Weiliang Huang ◽  
Maureen A. Kane ◽  
Rafael Villasmil ◽  
...  
Keyword(s):  
Amino Acid ◽  
Insertion Sequence ◽  
Experimental Studies ◽  
Spike Protein ◽  
Spike Glycoprotein ◽  
Furin Cleavage ◽  
New Host ◽  
S Protein ◽  
Furin Cleavage Site ◽  
Ribosome Pausing

The SARS-CoV-2 Spike glycoprotein (S protein) acquired a unique new 4 amino acid -PRRA- insertion sequence at amino acid residues (aa) 681–684 that forms a new furin cleavage site in S protein as well as several new glycosylation sites. We studied various statistical properties of the -PRRA- insertion at the RNA level (CCUCGGCGGGCA). The nucleotide composition and codon usage of this sequence are different from the rest of the SARS-CoV-2 genome. One of such features is two tandem CGG codons, although the CGG codon is the rarest codon in the SARS-CoV-2 genome. This suggests that the insertion sequence could cause ribosome pausing as the result of these rare codons. Due to population variants, the Nextstrain divergence measure of the CCU codon is extremely large. We cannot exclude that this divergence might affect host immune responses/effectiveness of SARS-CoV-2 vaccines, possibilities awaiting further investigation. Our experimental studies show that the expression level of original RNA sequence “wildtype” spike protein is much lower than for codon-optimized spike protein in all studied cell lines. Interestingly, the original spike sequence produces a higher titer of pseudoviral particles and a higher level of infection. Further mutagenesis experiments suggest that this dual-effect insert, comprised of a combination of overlapping translation pausing and furin sites, has allowed SARS-CoV-2 to infect its new host (human) more readily. This underlines the importance of ribosome pausing to allow efficient regulation of protein expression and also of cotranslational subdomain folding.

scholarly journals Emerging Therapeutics Based on the Amino Acid Neurotransmitter System: An Update on the Pharmaceutical Pipeline for Mood Disorders

2021 ◽  
Vol 5 ◽  
pp. 247054702110204
Author(s):  
Julia Hecking ◽  
Pasha A. Davoudian ◽  
Samuel T. Wilkinson
Keyword(s):  
Amino Acid ◽  
Mood Disorders ◽  
Phase Iii ◽  
Public Health Issue ◽  
Complex Nature ◽  
Novel Therapies ◽  
Amino Acid Neurotransmitters ◽  
Neurotransmitter System ◽  
Phase Iii Clinical Trials ◽  
The World

Mood disorders represent a pressing public health issue and significant source of disability throughout the world. The classical monoamine hypothesis, while useful in developing improved understanding and clinical treatments, has not fully captured the complex nature underlying mood disorders. Despite these shortcomings, the monoamine hypothesis continues to dominate the conceptual framework when approaching mood disorders. However, recent advances in basic and clinical research have led to a greater appreciation for the role that amino acid neurotransmitters play in the pathophysiology of mood disorders and as potential targets for novel therapies. In this article we review progress of compounds that focus on these systems. We cover both glutamate-targeting drugs such as: esketamine, AVP-786, REL-1017, AXS-05, rapastinel (GLYX-13), AV-101, NRX-101; as well as GABA-targeting drugs such as: brexanolone (SAGE-547), ganaxolone, zuranolone (SAGE-217), and PRAX-114. We focus the review on phase-II and phase-III clinical trials and evaluate the extant data and progress of these compounds.

scholarly journals Mutations within the Open Reading Frame (ORF) including Ochre stop codon of the Surface Glycoprotein gene of SARS-CoV-2 virus erase potential seed location motifs of human non-coding microRNAs.

2021 ◽  
Author(s):  
Krishna Himmatbhai Goyani ◽  
Shalin Vaniawala ◽  
Pratap Narayan Mukhopadhyaya
Keyword(s):  
Gene Sequence ◽  
Stop Codon ◽  
Early Stage ◽  
Amino Acid Position ◽  
Surface Glycoprotein ◽  
Nucleotide Polymorphisms ◽  
Cellular Mirnas ◽  
Synonymous Mutations ◽  
S Gene ◽  
Epidemic Period

MicroRNA are short and non-coding RNA, 18-25 nucleotides in length. They are produced at the early stage of viral infection. The roles played by cellular miRNAs and miRNA-mediated gene-silencing in the COVID-19 epidemic period is critical in order to develop novel therapeutics. We analysed SARS-CoV-2 Surface Glycoprotein (S) nucleotide sequence originating from India as well as Iran, Australia, Germany, Italy, Russia, China, Japan and Turkey and identified mutation in potential seed location of several human miRNA. Seventy single nucleotide polymorphisms (SNP) were detected in the S gene out of which, 36, 32 and 2 were cases of transitions, transversions and deletions respectively. Eleven human miRNA targets were identified on the reference S gene sequence with a score >80 in the miRDB database. Mutation A845S erased a common binding site of 7 human miRNA (miR-195-5p, miR-16-5p, miR-15b-5p, miR-15a-5p, miR-497-5p, miR-424-5p and miR-6838-5p). A synonymous mutation altered the wild type Ochre stop codon within the S gene sequence (Italy) to Opal thereby changing the seed sequence of miR-511-3p. Similar (synonymous) mutations were detected at amino acid position 659 and 1116 of the S gene where amino acids serine and threonine were retained, abolishing potential seed location for miR-219a-1-3p and miR-20b-3p respectively. The significance of this finding in reference to the strategy to use synthetic miRNA combinations as a novel therapeutic tool is discussed.

History, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19)

Coronaviruses ◽  
2021 ◽  
Vol 02 ◽  
Author(s):  
Amaresh Mishra ◽  
Nisha Nair ◽  
Vishwas Tripathi ◽  
Yamini Pathak ◽  
Jaseela Majeed
Keyword(s):  
Amino Acid ◽  
Severe Acute Respiratory Syndrome ◽  
Sequence Similarity ◽  
Neurological Complications ◽  
Amino Acid Sequences ◽  
World Health ◽  
Amino Acid Sequence Similarity ◽  
Effective Prevention ◽  
Short Period ◽  
The World

: The Coronavirus Disease 2019 (COVID-19), also known as a novel coronavirus (2019-nCoV), reportedly originated from Wuhan City, Hubei Province, China. Coronavirus Disease 2019 rapidly spread all over the world within a short period. On January 30th, 2020, the World Health Organization (WHO) declared it a global epidemic. COVID-19 is a severe acute respiratory syndrome coronavirus (SARS-CoV) virus that evolves to respiratory, hepatic, gastrointestinal, and neurological complications, and eventually death. SARS-CoV and the Middle East Respiratory Syndrome coronavirus (MERS-CoV) genome sequences similar identity with 2019-nCoV or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, few amino acid sequences of 2019-nCoV differ from SARS-CoV and MERS-CoV. COVID-19 shares about 90% amino acid sequence similarity with SARS-CoV. Effective prevention methods should be taken in order to control this pandemic situation. Till now, there are no effective treatments available to treat COVID-19. This review provides information regarding COVID-19 history, epidemiology, pathogenesis, and molecular diagnosis. Also, we focus on the development of vaccines in the management of this COVID-19 pandemic and limiting the spread of the virus.

scholarly journals Metalloprotease activity of CD13/aminopeptidase N on the surface of human myeloid cells

Blood ◽  
1990 ◽  
Vol 75 (2) ◽  
pp. 462-469 ◽  
Author(s):  
RA Ashmun ◽  
AT Look
Keyword(s):  
Amino Acid ◽  
Cell Surface ◽  
Myeloid Cells ◽  
Myeloid Cell ◽  
Aminopeptidase N ◽  
Surface Glycoprotein ◽  
Aminopeptidase Activity ◽  
Peptidase Activity ◽  
Cell Surface Glycoprotein ◽  
Metalloprotease Inhibitors

Abstract We previously found that the myeloid cell surface glycoprotein CD13 (gp150) is identical to aminopeptidase N (EC 3.4.11.2), a widely distributed membrane-bound, zinc-dependent metalloprotease with an extracellular enzymatic domain that cleaves N-terminal amino acid residues from oligopeptides (J Clin Invest 83:1299, 1989). As a first step toward defining the function of this molecule on myeloid cells, we assessed cell surface-associated N-terminal peptidase activity by sensitive spectrophotometric measurements of the cleavage of p- nitroanilide amino acid derivatives. Aminopeptidase activity detected on the surface of normal and malignant hematopoietic cells coincided with the level of cell surface CD13 expression as measured by flow cytometry. The enzyme was specifically inhibited by the zinc-binding metalloprotease inhibitors, bestatin, 1,10-phenanthroline, or 2.2′- dipyridyl, but was not affected by several inhibitors of other classes of proteases. Aminopeptidase activity was demonstrated for CD13 molecules specifically immunoprecipitated from the surface of CD13- positive cells and was blocked by the metalloprotease inhibitor 1,10- phenanthroline. Moreover, cell surface aminopeptidase activity was partially inhibited when viable cells were incubated with two of a panel of 11 monoclonal antibodies (MoAbs) known to be specific for extracellular epitopes of human CD13. This inhibition was apparent in the absence of detectable downmodulation of CD13 molecules from the cell surface, suggesting that these MoAbs either physically interfere with substrate binding or alter the zinc-coordinating properties of aminopeptidase N molecules. Aminopeptidase N could play an important role in modulating signals generated by peptides at the surface of myeloid cells, either by removing key N-terminal residues from active peptides or by converting inactive peptides to active forms. The inhibitory antibodies used in this study should prove useful in delineating the physiologic roles of CD13/aminopeptidase N on normal and malignant myeloid cells.

Bioinformatics Analysis of Laccase (Lac1) in Pycnoporus cinnabarinus

2010 ◽  
Vol 121-122 ◽  
pp. 502-506
Author(s):  
He Li ◽  
Guo Ying Zhou ◽  
Huai Yun Zhang ◽  
Liang Guo
Keyword(s):  
Amino Acid ◽  
Manganese Peroxidase ◽  
Bioinformatics Analysis ◽  
Instability Index ◽  
Pycnoporus Cinnabarinus ◽  
Grand Average ◽  
Glycosylation Sites ◽  
The World ◽  
Aliphatic Index

Pycnoporus cinnabarinus is a plant pathogen. It is common in many areas and is widely distributed throughout the world. Laccases of are some of the few oxidoreductases commercialized as industrial catalysts. In the present study, some characters of the amino acid sequence of P.cinnabarinus laccase (Lac1) were predicted and analyzed with the tools of bioinformatics. These results showed that the protein was composed of 20 kinds of amino acid; the theoretical pI of manganese peroxidase was 4.81 and the theoretical molecular weight of manganese peroxidase was 56292.0 Da; total number of atoms was 7806; the extinction coefficient was 58120 (280 nm). The N-terminal of the sequence considered was M (Met) and the estimated half-life was 30 hours (mammalian reticulocytes, in vitro). The instability index (II) was computed to be 34.50; this classifies the protein as stable. Aliphatic index was 82.64. Grand average of hydropathicity (GRAVY) was -0.063. There were 8 glycosylation sites, a signal peptide and conserved domains.

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