Zika Genome Sequences Set for Diagnostic, Vaccine Development Purposes

2016 ◽  
Vol 11 (12) ◽  
pp. 417-418
Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1061
Author(s):  
Wajdy J. Al-Awaida ◽  
Baker Jawabrah Al Hourani ◽  
Samer Swedan ◽  
Refat Nimer ◽  
Foad Alzoughool ◽  
...  

The outbreak of coronavirus disease 2019 (COVID-19), by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly developed into a worldwide pandemic. Mutations in the SARS-CoV-2 genome may affect various aspects of the disease including fatality ratio. In this study, 553,518 SARS-CoV-2 genome sequences isolated from patients from continents for the period 1 December 2020 to 15 March 2021 were comprehensively analyzed and a total of 82 mutations were identified concerning the reference sequence. In addition, associations between the mutations and the case fatality ratio (CFR), cases per million and deaths per million, were examined. The mutations having the highest frequencies among different continents were Spike_D614G and NSP12_P323L. Among the identified mutations, NSP2_T153M, NSP14_I42V and Spike_L18F mutations showed a positive correlation to CFR. While the NSP13_Y541C, NSP3_T73I and NSP3_Q180H mutations demonstrated a negative correlation to CFR. The Spike_D614G and NSP12_P323L mutations showed a positive correlation to deaths per million. The NSP3_T1198K, NS8_L84S and NSP12_A97V mutations showed a significant negative correlation to deaths per million. The NSP12_P323L and Spike_D614G mutations showed a positive correlation to the number of cases per million. In contrast, NS8_L84S and NSP12_A97V mutations showed a negative correlation to the number of cases per million. In addition, among the identified clades, none showed a significant correlation to CFR. The G, GR, GV, S clades showed a significant positive correlation to deaths per million. The GR and S clades showed a positive correlation to number of cases per million. The clades having the highest frequencies among continents were G, followed by GH and GR. These findings should be taken into consideration during epidemiological surveys of the virus and vaccine development.


mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Bhavna Hora ◽  
Naila Gulzar ◽  
Yue Chen ◽  
Konstantinos Karagiannis ◽  
Fangping Cai ◽  
...  

ABSTRACT High-throughput sequencing (HTS) has been widely used to characterize HIV-1 genome sequences. There are no algorithms currently that can directly determine genotype and quasispecies population using short HTS reads generated from long genome sequences without additional software. To establish a robust subpopulation, subtype, and recombination analysis workflow, we amplified the HIV-1 3′-half genome from plasma samples of 65 HIV-1-infected individuals and sequenced the entire amplicon (∼4,500 bp) by HTS. With direct analysis of raw reads using HIVE-hexahedron, we showed that 48% of samples harbored 2 to 13 subpopulations. We identified various subtypes (17 A1s, 4 Bs, 27 Cs, 6 CRF02_AGs, and 11 unique recombinant forms) and defined recombinant breakpoints of 10 recombinants. These results were validated with viral genome sequences generated by single genome sequencing (SGS) or the analysis of consensus sequence of the HTS reads. The HIVE-hexahedron workflow is more sensitive and accurate than just evaluating the consensus sequence and also more cost-effective than SGS. IMPORTANCE The highly recombinogenic nature of human immunodeficiency virus type 1 (HIV-1) leads to recombination and emergence of quasispecies. It is important to reliably identify subpopulations to understand the complexity of a viral population for drug resistance surveillance and vaccine development. High-throughput sequencing (HTS) provides improved resolution over Sanger sequencing for the analysis of heterogeneous viral subpopulations. However, current methods of analysis of HTS reads are unable to fully address accurate population reconstruction. Hence, there is a dire need for a more sensitive, accurate, user-friendly, and cost-effective method to analyze viral quasispecies. For this purpose, we have improved the HIVE-hexahedron algorithm that we previously developed with in silico short sequences to analyze raw HTS short reads. The significance of this study is that our standalone algorithm enables a streamlined analysis of quasispecies, subtype, and recombination patterns from long HIV-1 genome regions without the need of additional sequence analysis tools. Distinct viral populations and recombination patterns identified by HIVE-hexahedron are further validated by comparison with sequences obtained by single genome sequencing (SGS).


2020 ◽  
Author(s):  
Arun Shanker ◽  
Divya Bhanu ◽  
Anajani Alluri

The family of viruses belonging to Coronaviridae mainly consist of virulent pathogens that have a zoonotic property, Severe Respiratory Syndrome (SARS-CoV) and Middle East Respiratory Syndrome (MERS-CoV) of this family have emerged before and now the Novel COVID-19 has emerged in China. Characterization of spike glycoproteins, polyproteins and other viral proteins from viruses are important for vaccine development. Homology modelling of these proteins with known templates offers the opportunity to discover ligand binding sites and possible antiviral properties of these protein ligand complexes. Any information emerging from these protein models can be used for vaccine development. In this study we did a complete bioinformatic analysis, sequence alignment, comparison of multiple sequences and homology modelling of the Novel COVID-19 whole genome sequences, the spike protein and the polyproteins for homology with known proteins, we also analysed receptor binding sites in these models for possible vaccine development. Our results showed that the tertiary structure of the polyprotein isolate COVID-19 _HKU-SZ-001_2020 had 98.94 percent identity with SARS-Coronavirus NSP12 bound to NSP7 and NSP8 co-factors. Our results indicate that a part of the viral genome (residues 254 to 13480 in Frame 2 with 4409 amino acids) of the Novel COVID-19 virus isolate Wuhan-Hu-1 (Genbank Accession Number MN908947.3) when modelled with template 2a5i of the PDB database had 96 percent identity with a 3C like peptidase of SARS-CoV which has ability to bind with Aza-Peptide Epoxide (APE) which is known for irreversible inhibition of SARS-CoV main peptidase. The part of the genome when modelled with template 3e9s of the PDB database had 82 percent identity with a papain-like protease/deubiquitinase which when complexed with ligand GRL0617 acts as inhibitor which can block SARS-CoV replication. It is possible that these viral inhibiters can be used for vaccine development for the Novel COVID-19.


Author(s):  
L Ponoop Prasad Patro ◽  
Chakkarai Sathyaseelan ◽  
Patil Pranita Uttamrao ◽  
Thenmalarchelvi Rathinavelan

ABSTRACTTo accelerate the drug and vaccine development against the severe acute respiratory syndrome virus 2 (SARS-CoV-2), a comparative analysis of SARS-CoV-2 proteome has been performed in two phases by considering manually curated 31389 whole genome sequences from 84 countries. Among the 9 mutations that occur at a high significance (T85I-NPS2, L37F-NSP6, P323L-NSP12, D614G-spike, Q57H-ORF3a, G251V-ORF3a, L84S-ORF8, R203K-nucleocapsid and G204R-nucleocapsid), R203K-nucleocapsid and G204R-nucleocapsid are co-occurring (dependent) mutations and P323L-NSP12 and D614G-spike often appear simultaneously. Other notable variations that appear with a moderate to low significance are, M85-NSP1 deletion, D268-NSP2 deletion, 112 amino acids deletion in ORF8, a phenylalanine insertion amidst F34-F36 (NSP6) and several co-existing (dependent) substitution/deletion (I559V & P585S in NSP2, P504L & Y541C in NSP13, G82 & H83 deletions in NSP1 and K141, S142 & F143 deletions in NSP2) mutations. P323L-NSP12, D614G-spike, L37F-NSP6, L84S-ORF8 and the sequences deficient of the high significant mutations have led to 4 major SARS-CoV-2 clades. The top 5 countries bearing all the high significant and majority of the moderate significant mutations are: USA, England, Wales, Australia and Scotland. Further, the majority of the significant mutations have evolved in the first phase and have already transmitted around the globe indicating the positive selection pressure. Among the 26 SARS-CoV-2 proteins, nucleocapsid protein, ORF3a, ORF8, RNA dependent RNA polymerase and spike exhibit a higher heterogeneity compared with the rest of the proteins. However, NSP9, NSP10, NSP8, the envelope protein and NSP4 are highly resistant to mutations and can be exploited for drug/vaccine development.


2012 ◽  
Vol 93 (4) ◽  
pp. 866-875 ◽  
Author(s):  
Jelle Matthijnssens ◽  
Samuel Miño ◽  
Hajnalka Papp ◽  
Christiaan Potgieter ◽  
Luis Novo ◽  
...  

In this study, the complete genome sequences of seven equine group A rotavirus (RVA) strains (RVA/Horse-tc/GBR/L338/1991/G13P[18], RVA/Horse-wt/IRL/03V04954/2003/G3P[12] and RVA/Horse-wt/IRL/04V2024/2004/G14P[12] from Europe; RVA/Horse-wt/ARG/E30/1993/G3P[12], RVA/Horse-wt/ARG/E403/2006/G14P[12] and RVA/Horse-wt/ARG/E4040/2008/G14P[12] from Argentina; and RVA/Horse-wt/ZAF/EqRV-SA1/2006/G14P[12] from South Africa) were determined. Multiple novel genotypes were identified and genotype numbers were assigned by the Rotavirus Classification Working Group: R9 (VP1), C9 (VP2), N9 (NSP2), T12 (NSP3), E14 (NSP4), and H7 and H11 (NSP5). The genotype constellation of L338 was unique: G13-P[18]-I6-R9-C9-M6-A6-N9-T12-E14-H11. The six remaining equine RVA strains showed a largely conserved genotype constellation: G3/G14-P[12]-I2/I6-R2-C2-M3-A10-N2-T3-E2/E12-H7, which is highly divergent from other known non-equine RVA genotype constellations. Phylogenetic analyses revealed that the sequences of these equine RVA strains are related distantly to non-equine RVA strains, and that at least three lineages exist within equine RVA strains. A small number of reassortment events were observed. Interestingly, the three RVA strains from Argentina possessed the E12 genotype, whereas the three RVA strains from Ireland and South Africa possessed the E2 genotype. The unusual E12 genotype has until now only been described in Argentina among RVA strains collected from guanaco, cattle and horses, suggesting geographical isolation of this NSP4 genotype. This conserved genetic configuration of equine RVA strains could be useful for future vaccine development or improvement of currently used equine RVA vaccines.


2020 ◽  
Author(s):  
Arun Shanker ◽  
Anjani Alluri ◽  
Divya Bhanu

<p></p><p>The family of viruses belonging to Coronaviridae mainly consist of virulent pathogens that have a zoonotic property, Severe Respiratory Syndrome (SARS-CoV) and Middle East Respiratory Syndrome (MERS-CoV) of this family have emerged before and now the SARS-CoV-2 has emerged in China. Characterization of spike glycoproteins, polyproteins and other viral proteins from viruses are important for vaccine development. Homology modelling of these proteins with known templates offers the opportunity to discover ligand binding sites and explore the possible antiviral properties of these protein ligand complexes. Any information emerging from these protein models can be used for vaccine development. In this study we did a complete bioinformatic analysis, sequence alignment, comparison of multiple sequences and homology modelling of the <a>SARS-CoV-2 </a>whole genome sequences, the spike protein and the polyproteins for homology with known proteins, we also analysed receptor binding sites in these models for possible binding with ligands that exhibit antiviral properties. Our results showed that the tertiary structure of the polyprotein isolate SARS-CoV-2_HKU-SZ-001_2020 had 98.94 percent identity with SARS-Coronavirus NSP12 bound to NSP7 and NSP8 co-factors. <a>Our results indicate that a part of the viral genome </a><a>(residues 3268 -3573 in Frame 2 with 306 amino acids) of the SARS-CoV-2 virus isolate Wuhan-Hu-1 (Genbank Accession Number MN908947.3) </a>when modelled with template 2a5i of the PDB database had 96 percent identity with a 3C like peptidase of SARS-CoV which has ability to bind with Aza-Peptide Epoxide (APE) which is known for irreversible inhibition of SARS-CoV main peptidase. The part of the genome (residues 1568-1882 in Frame 2 with 315 amino acids) when modelled with template 3e9s of the PDB database had 82 percent identity with a papain-like protease/deubiquitinase which when complexed with ligand GRL0617 acts as inhibitor which can block SARS-CoV replication. It is possible that these viral inhibiters can be used for vaccine development for the SARS-CoV-2.</p><p></p><p></p>


2020 ◽  
Author(s):  
Arun Shanker ◽  
Divya Bhanu ◽  
Anajani Alluri

<p></p><p>The family of viruses belonging to Coronaviridae mainly consist of virulent pathogens that have a zoonotic property, Severe Respiratory Syndrome (SARS-CoV) and Middle East Respiratory Syndrome (MERS-CoV) of this family have emerged before and now the Novel COVID-19 has emerged in China. Characterization of spike glycoproteins, polyproteins and other viral proteins from viruses are important for vaccine development. Homology modelling of these proteins with known templates offers the opportunity to discover ligand binding sites and possible antiviral properties of these protein ligand complexes. Any information emerging from these protein models can be used for vaccine development. In this study we did a complete bioinformatic analysis, sequence alignment, comparison of multiple sequences and homology modelling of the Novel COVID-19 whole genome sequences, the spike protein and the polyproteins for homology with known proteins, we also analysed receptor binding sites in these models for possible vaccine development. Our results showed that the tertiary structure of the polyprotein isolate COVID-19 _HKU-SZ-001_2020 had 98.94 percent identity with SARS-Coronavirus NSP12 bound to NSP7 and NSP8 co-factors. Our results indicate that a part of the viral genome (residues 254 to 13480 in Frame 2 with 4409 amino acids) of the Novel COVID-19 virus isolate Wuhan-Hu-1 (Genbank Accession Number MN908947.3) when modelled with template 2a5i of the PDB database had 96 percent identity with a 3C like peptidase of SARS-CoV which has ability to bind with Aza-Peptide Epoxide (APE) which is known for irreversible inhibition of SARS-CoV main peptidase. The part of the genome when modelled with template 3e9s of the PDB database had 82 percent identity with a papain-like protease/deubiquitinase which when complexed with ligand GRL0617 acts as inhibitor which can block SARS-CoV replication. It is possible that these viral inhibiters can be used for vaccine development for the Novel COVID-19.</p><p></p><p></p>


2020 ◽  
Author(s):  
Arun Shanker ◽  
Anjani Alluri ◽  
Divya Bhanu

<p></p><p>The family of viruses belonging to Coronaviridae mainly consist of virulent pathogens that have a zoonotic property, Severe Respiratory Syndrome (SARS-CoV) and Middle East Respiratory Syndrome (MERS-CoV) of this family have emerged before and now the Novel COVID-19 has emerged in China. Characterization of spike glycoproteins, polyproteins and other viral proteins from viruses are important for vaccine development. Homology modelling of these proteins with known templates offers the opportunity to discover ligand binding sites and possible antiviral properties of these protein ligand complexes. Any information emerging from these protein models can be used for vaccine development. In this study we did a complete bioinformatic analysis, sequence alignment, comparison of multiple sequences and homology modelling of the Novel COVID-19 whole genome sequences, the spike protein and the polyproteins for homology with known proteins, we also analysed receptor binding sites in these models for possible vaccine development. Our results showed that the tertiary structure of the polyprotein isolate COVID-19 _HKU-SZ-001_2020 had 98.94 percent identity with SARS-Coronavirus NSP12 bound to NSP7 and NSP8 co-factors. Our results indicate that a part of the viral genome (residues 254 to 13480 in Frame 2 with 4409 amino acids) of the Novel COVID-19 virus isolate Wuhan-Hu-1 (Genbank Accession Number MN908947.3) when modelled with template 2a5i of the PDB database had 96 percent identity with a 3C like peptidase of SARS-CoV which has ability to bind with Aza-Peptide Epoxide (APE) which is known for irreversible inhibition of SARS-CoV main peptidase. The part of the genome when modelled with template 3e9s of the PDB database had 82 percent identity with a papain-like protease/deubiquitinase which when complexed with ligand GRL0617 acts as inhibitor which can block SARS-CoV replication. It is possible that these viral inhibiters can be used for vaccine development for the Novel COVID-19.</p><p></p><p></p>


Pathogens ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 584 ◽  
Author(s):  
Eric Dumonteil ◽  
Claudia Herrera

The ongoing SARS-CoV-2 pandemic has triggered multiple efforts for serological tests and vaccine development. Most of these tests and vaccines are based on the Spike glycoprotein (S) or the Nucleocapsid (N) viral protein. Conservation of these antigens among viral strains is critical to ensure optimum diagnostic test performance and broad protective efficacy, respectively. We assessed N and S antigen diversity from 17,853 SARS-CoV-2 genome sequences and evaluated selection pressure. Up to 6–7 incipient phylogenetic clades were identified for both antigens, confirming early variants of the S antigen and identifying new ones. Significant diversifying selection was detected at multiple sites for both antigens. Some sequence variants have already spread in multiple regions, in spite of their low frequency. In conclusion, the N and S antigens of SARS-CoV-2 are well-conserved antigens, but new clades are emerging and may need to be included in future diagnostic and vaccine formulations.


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