scholarly journals Structural and Genetic Analysis of Coronaviruses Spike Proteins Suggest Pangolin as a Proximate Intermediate Host of SARS-CoV-2 (COVID-19)

2020 ◽  
Author(s):  
Sohail Raza ◽  
Muhammad Asif Rasheed ◽  
Wajeeha Zahir ◽  
Muhammad Tariq Navid ◽  
Rana Aamir Diwan ◽  
...  
Keyword(s):  
Intermediate Host ◽  
Structure Alignment ◽  
World Health ◽  
Computer Assisted ◽  
Protein Structure Alignment ◽  
Reference Structure ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Phylogenetics Analysis ◽  
Spike Proteins

During December 2019, a novel coronavirus named SARS-CoV-2 has emerged in Wuhan, China. The human to human transmission of this virus has also been established. The virus has so far infected more than 2 million people and spread over 200 countries. The World Health Organization (WHO) has declared COVID-19 a global health emergency due to its spread well beyond China. It has been established that this virus originates from bats and uses an intermediate host for transfer to humans. The knowledge about the intermediate host is important to find the virus shuttle mechanism to stop future outbreaks. For this, the genetic and structural analysis of coronaviruses spike proteins was performed using a computer-assisted approach.To conduct the In silico analysis, 43 sequences of spike protein belong to different species were retrieved from the NCBI nucleotide database. Pairwise and multiple sequence alignments were performed to check the similarities and differences of the retrieved sequences. Moreover, to highlight relationships among different species, phylogenetics analysis was performed using the MEGA software tool. In the end, protein structure alignment (superimposition) was performed against the reference structure by UCSF Chimera software. The results highlighted that the maximum similarity of human protein was found against Bat and Pangolinsequences. Moreover, among Bat and Pangolin, the highest similarity was found against pangolin based on phylogenetics analysis. These results suggest that SARS-CoV-2 transfers from bats to humans through pangolins.

scholarly journals Analysis of the Spike Proteins Suggest Pangolin as an Intermediate Host of COVID-19 (SARS-CoV-2)

2021 ◽  
Vol 25 (03) ◽  
pp. 639-644
Author(s):  
Sohail Raza
Keyword(s):  
Phylogenetic Analysis ◽  
Intermediate Host ◽  
Human Population ◽  
Genomic Analysis ◽  
In Silico Analysis ◽  
Computer Assisted ◽  
Reference Structure ◽  
Multiple Sequence ◽  
S Protein ◽  
Transmission Potential

The novel coronavirus (SARS-CoV-2) is a third member of its group that has introduced public health catastrophes around the globe. Since, its emergence in Wuhan, China by December 2019, SARS-CoV-2 infected millions of human population along with many casualties globally. The transmission potential of SARS-CoV-2 between humans has already been studied. Despite this transmission in human population, the primary origin of SARS-CoV-2 has been linked with bats by the help of an intermediate (secondary) host. This study was assumed to investigate the possible secondary or intermediate host to shuttle down the SARS-CoV-2 transmission and further to mitigate future pandemics. The antigenic surface/spike (S) protein was used for the structural and genomic analysis through currently available computer assisted technology. For the In-silico analysis, 43 sequences of S-protein of coronaviruses originated in various species were retrieved from nucleotide database of NCBI. These sequences were matched to find any similarities/differences by employing pairwise and multiple sequence alignment. The phylogenetic analysis was conducted to observe the relation among different species through MEGA software. Finally, comparative analysis for structures of S-protein (superimposition) was done with reference structure by using UCSF Chimera software. The results of this study expressed maximum match of S-protein sequences of human coronavirus with Bat and with Pangolin sequences respectively. The Phylogenetic analysis between Bat and Pangolin showed that SARS-CoV-2 transmitted from bats to humans possibly through the intermediate host of Pangolin. © 2021 Friends Science Publishers

scholarly journals Evolutionary Relationships and Sequence-Structure Determinants in Human SARS Coronavirus-2 Spike Proteins for Host Receptor Recognition

2020 ◽  
Author(s):  
Lalitha Guruprasad
Keyword(s):  
Phylogenetic Trees ◽  
Disulfide Bridge ◽  
Sequence Motifs ◽  
Structural Determinants ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Angiotensin Converting Enzyme 2 ◽  
Multiple Sequence Alignments ◽  
Loop 2 ◽  
Spike Proteins

<div>Coronavirus disease 2019 (COVID-19) is a pandemic infectious disease caused by novel Severe Acute Respiratory Syndrome coronavirus-2 (SARS CoV-2). The SARS CoV-2 is transmitted more rapidly and readily than SARS CoV. Both, SARS CoV and SARS CoV-2 via their glycosylated spike proteins recognize the human angiotensin converting enzyme-2 (ACE-2) receptor. We generated multiple sequence alignments and phylogenetic trees for representative spike proteins of CoV and CoV-2 from various host sources in order to analyze the specificity in SARS CoV-2 spike proteins required for causing infection in humans. Our results show that two sequence motifs in the N-terminal domain; "MESEFR" and "SYLTPG" are specific to human SARS CoV-2 and pangolin SARS CoV. In the receptor binding domain (RBD), three sequence loops; VGGNY (loop 1), YQAGSTPC (loop 2), EGFNCY (loop 3) and a tethered disulfide bridge Cys480-Cys488 connecting loops 2 and 3 are structural determinants for the recognition of human ACE-2 receptor. The complete genome analysis of representative SARS CoVs from bat, civet, pangolin, human host sources and human SARS CoV-2 identified the bat genome (GenBank code: MN996532.1) and the pangolin SARS CoV genomes as closest to the recent novel human SARS CoV-2 genomes. The bat CoV genomes (GenBank codes: MG772933 and MG772934) are evolutionary intermediates in the mutagenesis progression towards becoming human SARS CoV-2. </div>

scholarly journals Evolutionary Relationships and Sequence-Structure Determinants in Human SARS Coronavirus-2 Spike Proteins for Host Receptor Recognition

2020 ◽  
Author(s):  
Lalitha Guruprasad
Keyword(s):  
Phylogenetic Trees ◽  
Disulfide Bridge ◽  
Sequence Motifs ◽  
Structural Determinants ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Angiotensin Converting Enzyme 2 ◽  
Multiple Sequence Alignments ◽  
Loop 2 ◽  
Spike Proteins

Coronavirus disease 2019 (COVID-19) is a pandemic infectious disease caused by novel Severe Acute Respiratory Syndrome coronavirus-2 (SARS CoV-2). The SARS CoV-2 is transmitted more rapidly and readily than SARS CoV. Both, SARS CoV and SARS CoV-2 via their glycosylated spike proteins recognize the human angiotensin converting enzyme-2 (ACE-2) receptor. We generated multiple sequence alignments and phylogenetic trees for representative spike proteins of CoV and CoV-2 from various host sources in order to analyze the specificity in SARS CoV-2 spike proteins required for causing infection in humans. Our results show that two sequence motifs in the N-terminal domain; "MESEFR" and "SYLTPG" are specific to human SARS CoV-2 and pangolin SARS CoV. In the receptor binding domain (RBD), three sequence loops; VGGNY (loop 1), YQAGSTPC (loop 2), EGFNCY (loop 3) and a tethered disulfide bridge Cys480-Cys488 connecting loops 2 and 3 are structural determinants for the recognition of human ACE-2 receptor. The complete genome analysis of representative SARS CoVs from bat, civet, pangolin, human host sources and human SARS CoV-2 identified the bat genome (GenBank code: MN996532.1) and the pangolin SARS CoV genomes as closest to the recent novel human SARS CoV-2 genomes. The bat CoV genomes (GenBank codes: MG772933 and MG772934) are evolutionary intermediates in the mutagenesis progression towards becoming human SARS CoV-2.

scholarly journals Evolutionary Relationships and Sequence-Structure Determinants in Human SARS Coronavirus-2 Spike Proteins for Host Receptor Recognition

2020 ◽  
Author(s):  
Lalitha Guruprasad
Keyword(s):  
Phylogenetic Trees ◽  
Disulfide Bridge ◽  
Sequence Motifs ◽  
Structural Determinants ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Angiotensin Converting Enzyme 2 ◽  
Multiple Sequence Alignments ◽  
Complete Genome Analysis ◽  
Spike Proteins

<div>Coronavirus disease 2019 (COVID-19) is a pandemic infectious disease caused by novel Severe Acute Respiratory Syndrome coronavirus-2 (SARS CoV-2). The SARS CoV-2 is transmitted more rapidly and readily than SARS CoV. Both, SARS CoV and SARS CoV-2 via their glycosylated spike proteins recognize the human angiotensin converting enzyme-2 (ACE-2) receptor. We generated multiple sequence alignments and phylogenetic trees for representative spike proteins of CoV and CoV-2 from various host sources in order to analyze the specificity in SARS CoV-2 spike proteins required for causing infection in humans. Our results show that two sequence motifs in the N-terminal domain; "MESEFR" and "SYLTPG" are specific to human SARS CoV-2. In the receptor binding domain (RBD), two sequence motifs; "VGGNY" and "EIYQAGSTPCNGV" and a disulfide bridge connecting 480C and 488C in the extended loop are structural determinants for the recognition of human ACE-2 receptor. The complete genome analysis of representative SARS CoVs from bat, civet, human host sources and human SARS CoV-2 identified the bat genome (GenBank code: MN996532.1) as closest to the recent novel human SARS CoV-2 genomes. The bat CoV genomes (GenBank codes: MG772933 and MG772934) are evolutionary intermediates in the mutagenesis progression towards becoming human SARS CoV-2. <br></div>

scholarly journals Positive natural selection in primate genes of the type I interferon response

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Elena N. Judd ◽  
Alison R. Gilchrist ◽  
Nicholas R. Meyerson ◽  
Sara L. Sawyer
Keyword(s):  
Natural Selection ◽  
Positive Selection ◽  
Type I Interferon ◽  
Interferon Response ◽  
Type I ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Multiple Sequence Alignments ◽  
Interferon Stimulated Genes ◽  
Interferon Induction

Abstract Background The Type I interferon response is an important first-line defense against viruses. In turn, viruses antagonize (i.e., degrade, mis-localize, etc.) many proteins in interferon pathways. Thus, hosts and viruses are locked in an evolutionary arms race for dominance of the Type I interferon pathway. As a result, many genes in interferon pathways have experienced positive natural selection in favor of new allelic forms that can better recognize viruses or escape viral antagonists. Here, we performed a holistic analysis of selective pressures acting on genes in the Type I interferon family. We initially hypothesized that the genes responsible for inducing the production of interferon would be antagonized more heavily by viruses than genes that are turned on as a result of interferon. Our logic was that viruses would have greater effect if they worked upstream of the production of interferon molecules because, once interferon is produced, hundreds of interferon-stimulated proteins would activate and the virus would need to counteract them one-by-one. Results We curated multiple sequence alignments of primate orthologs for 131 genes active in interferon production and signaling (herein, “induction” genes), 100 interferon-stimulated genes, and 100 randomly chosen genes. We analyzed each multiple sequence alignment for the signatures of recurrent positive selection. Counter to our hypothesis, we found the interferon-stimulated genes, and not interferon induction genes, are evolving significantly more rapidly than a random set of genes. Interferon induction genes evolve in a way that is indistinguishable from a matched set of random genes (22% and 18% of genes bear signatures of positive selection, respectively). In contrast, interferon-stimulated genes evolve differently, with 33% of genes evolving under positive selection and containing a significantly higher fraction of codons that have experienced selection for recurrent replacement of the encoded amino acid. Conclusion Viruses may antagonize individual products of the interferon response more often than trying to neutralize the system altogether.

scholarly journals Respiratory syncytial virus B sequence analysis reveals a novel early genotype

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Juan C. Muñoz-Escalante ◽  
Andreu Comas-García ◽  
Sofía Bernal-Silva ◽  
Daniel E. Noyola
Keyword(s):  
Molecular Markers ◽  
Respiratory Syncytial Virus ◽  
Maximum Likelihood ◽  
Respiratory Infections ◽  
Phylogenetic Analyses ◽  
Detection Methods ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Individual Gene ◽  
Syncytial Virus

AbstractRespiratory syncytial virus (RSV) is a major cause of respiratory infections and is classified in two main groups, RSV-A and RSV-B, with multiple genotypes within each of them. For RSV-B, more than 30 genotypes have been described, without consensus on their definition. The lack of genotype assignation criteria has a direct impact on viral evolution understanding, development of viral detection methods as well as vaccines design. Here we analyzed the totality of complete RSV-B G gene ectodomain sequences published in GenBank until September 2018 (n = 2190) including 478 complete genome sequences using maximum likelihood and Bayesian phylogenetic analyses, as well as intergenotypic and intragenotypic distance matrices, in order to generate a systematic genotype assignation. Individual RSV-B genes were also assessed using maximum likelihood phylogenetic analyses and multiple sequence alignments were used to identify molecular markers associated to specific genotypes. Analyses of the complete G gene ectodomain region, sequences clustering patterns, and the presence of molecular markers of each individual gene indicate that the 37 previously described genotypes can be classified into fifteen distinct genotypes: BA, BA-C, BA-CC, CB1-THB, GB1-GB4, GB6, JAB1-NZB2, SAB1, SAB2, SAB4, URU2 and a novel early circulating genotype characterized in the present study and designated GB0.

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