scholarly journals Emerging SARS-CoV-2 variants follow a historical pattern recorded in outgroups infecting non-human hosts

2021 ◽  
Author(s):  
Kazutaka Katoh ◽  
Daron M. Standley
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitutions ◽  
Evolutionary Analysis ◽  
Evolutionary Mechanism ◽  
S Protein ◽  
Historical Pattern ◽  
Molecular Evolutionary Analysis

Abstract The ability to predict emerging variants of SARS-CoV-2 would be of enormous value, as it would enable proactive design of vaccines in advance of such emergence. Based on molecular evolutionary analysis of the S protein, we found a significant correspondence in the location of amino acid substitutions between SARS-CoV-2 variants recently emerging and their relatives that infected bat and pangolin before the pandemic. This observation suggests that a limited number of sites in this protein are repeatedly substituted in different lineages of this group of viruses. It follows, therefore, that the sites of future emerging mutations in SARS-CoV-2 can be predicted by analyzing their relatives (outgroups) that have infected non-human hosts. We discuss a possible evolutionary mechanism behind these substitutions and provide a list of frequently substituted sites that potentially include future emerging variants in SARS-CoV-2.

scholarly journals Emerging SARS-CoV-2 variants follow a historical pattern recorded in outgroups infecting non-human hosts

2021 ◽  
Author(s):  
Kazutaka Katoh ◽  
Daron M. Standley
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitutions ◽  
Evolutionary Analysis ◽  
Evolutionary Mechanism ◽  
S Protein ◽  
Historical Pattern ◽  
Molecular Evolutionary Analysis

Abstract The ability to predict emerging variants of SARS-CoV-2 would be of enormous value, as it would enable proactive design of vaccines in advance of such emergence. Based on molecular evolutionary analysis of the S protein, we found a significant correspondence in the location of amino acid substitutions between SARS-CoV-2 variants recently emerging and their relatives that infected bat and pangolin before the pandemic. This observation suggests that a limited number of sites in this protein are repeatedly substituted in different lineages of this group of viruses. It follows, therefore, that the sites of future emerging mutations in SARS-CoV-2 can be predicted by analyzing their relatives (outgroups) that have infected non-human hosts. We discuss a possible evolutionary mechanism behind these substitutions and provide a list of frequently substituted sites that potentially include future emerging variants in SARS-CoV-2.

scholarly journals A simple method for predicting emerging SARS-CoV-2 variants using outgroups infecting non-human hosts

2021 ◽  
Author(s):  
Kazutaka Katoh ◽  
Daron M. Standley
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitutions ◽  
Evolutionary Analysis ◽  
Simple Method ◽  
Evolutionary Mechanism ◽  
S Protein ◽  
Molecular Evolutionary Analysis

Abstract The ability to predict emerging variants of SARS-CoV-2 would be of enormous value, as it would enable proactive design of vaccines in advance of such emergence. Based on molecular evolutionary analysis of S protein, we found a significant correspondence in the location of amino acid substitutions between SARS-CoV-2 variants recently emerging and their relatives that infected bat and pangolin before the pandemic. This observation suggests that a limited number of sites in this protein are repeatedly substituted in independent lineages of this group of viruses. It follows, therefore, that the sites of future emerging mutations in SARS-CoV-2 can be predicted by analyzing their relatives (outgroups) that have infected non-human hosts. We discuss a possible evolutionary mechanism behind these substitutions and provide a list of frequently substituted sites that potentially include future emerging variants in SARS-CoV-2.

scholarly journals Natural variants in SARS-CoV-2 Spike protein pinpoint structural and functional hotspots with implications for prophylaxis and therapeutic strategies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Suman Pokhrel ◽  
Benjamin R. Kraemer ◽  
Scott Burkholz ◽  
Daria Mochly-Rosen
Keyword(s):  
Amino Acid ◽  
Severe Disease ◽  
Single Amino Acid ◽  
Amino Acid Substitutions ◽  
Severe Respiratory Distress ◽  
S Protein ◽  
Individual Sequences ◽  
Natural Variants ◽  
Novel Coronavirus ◽  
The Individual

AbstractIn December 2019, a novel coronavirus, termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified as the cause of pneumonia with severe respiratory distress and outbreaks in Wuhan, China. The rapid and global spread of SARS-CoV-2 resulted in the coronavirus 2019 (COVID-19) pandemic. Earlier during the pandemic, there were limited genetic viral variations. As millions of people became infected, multiple single amino acid substitutions emerged. Many of these substitutions have no consequences. However, some of the new variants show a greater infection rate, more severe disease, and reduced sensitivity to current prophylaxes and treatments. Of particular importance in SARS-CoV-2 transmission are mutations that occur in the Spike (S) protein, the protein on the viral outer envelope that binds to the human angiotensin-converting enzyme receptor (hACE2). Here, we conducted a comprehensive analysis of 441,168 individual virus sequences isolated from humans throughout the world. From the individual sequences, we identified 3540 unique amino acid substitutions in the S protein. Analysis of these different variants in the S protein pinpointed important functional and structural sites in the protein. This information may guide the development of effective vaccines and therapeutics to help arrest the spread of the COVID-19 pandemic.

Molecular evolutionary analysis based on the amino acid sequence of catalase

1993 ◽  
Vol 37 (1) ◽  
pp. 71-76 ◽  
Author(s):  
Ingemar von Ossowski ◽  
Georg Hausner ◽  
Peter C. Loewen
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Evolutionary Analysis ◽  
Molecular Evolutionary Analysis

scholarly journals Amino Acid Substitutions in the S2 Region Enhance Severe Acute Respiratory Syndrome Coronavirus Infectivity in Rat Angiotensin-Converting Enzyme 2-Expressing Cells

2007 ◽  
Vol 81 (19) ◽  
pp. 10831-10834 ◽  
Author(s):  
Shuetsu Fukushi ◽  
Tetsuya Mizutani ◽  
Kouji Sakai ◽  
Masayuki Saijo ◽  
Fumihiro Taguchi ◽  
...  
Keyword(s):  
Amino Acid ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Host Species ◽  
Molecular Basis ◽  
Amino Acid Substitutions ◽  
Converting Enzyme ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Virus Adaptation

ABSTRACT To clarify the molecular basis of severe acute respiratory syndrome coronavirus (SARS-CoV) adaptation to different host species, we serially passaged SARS-CoV in rat angiotensin-converting enzyme 2 (ACE2)-expressing cells. After 15 passages, the virus (Rat-P15) came to replicate effectively in rat ACE2-expressing cells. Two amino acid substitutions in the S2 region were found on the Rat-P15 S gene. Analyses of the infectivity of the pseudotype-bearing S protein indicated that the two substitutions in the S2 region, especially the S950F substitution, were responsible for efficient infection. Therefore, virus adaptation to different host species can be induced by amino acid substitutions in the S2 region.

scholarly journals Mutational spectra of SARS-CoV-2 isolated from animals

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10609
Author(s):  
Ahmed Elaswad ◽  
Mohamed Fawzy ◽  
Shereen Basiouni ◽  
Awad A. Shehata
Keyword(s):  
Amino Acid ◽  
Wide Spectrum ◽  
Geographic Region ◽  
Heptad Repeat ◽  
Binding Motif ◽  
Amino Acid Substitutions ◽  
Furin Cleavage ◽  
S Protein ◽  
Furin Cleavage Site ◽  
Unique Amino Acid

Coronaviruses are ubiquitous and infect a wide spectrum of animals and humans. The newly emerged severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a worldwide pandemic. To address the role that animals may play in the evolution of SARS-CoV-2, the full genome sequences of SARS-CoV-2 isolated from animals were compared with SARS-CoV-2 human isolates from the same clade and geographic region. Phylogenetic analysis of SARS-CoV-2 isolated from the cat, dog, mink, mouse, and tiger revealed a close relationship with SARS-CoV-2 human isolates from the same clade and geographic region with sequence identities of 99.94–99.99%. The deduced amino acid sequence of spike (S) protein revealed the presence of a furin cleavage site (682RRAR▾685), which did not differ among all SARS-CoV-2 isolates from animals and humans. SARS-CoV-2 isolates from minks exhibited two amino acid substitutions (G261D, A262S) in the N-terminal domain of S protein and four (L452M, Y453F, F486L, N501T) in the receptor-binding motif (RBM). In the mouse, the S protein had two amino acid substitutions, one in the RBM (Q498H) and the other (N969S) in the heptad repeat 1. SARS-CoV-2 isolated from minks furtherly exhibited three unique amino acid substitutions in the nucleocapsid (N)protein. In the cat, two unique amino acid substitutions were discovered in the N (T247I) and matrix (T175M) proteins. Additionally, SARS-CoV-2 isolated from minks possessed sixteen, four, and two unique amino acid substitutions in the open reading frame 1ab (ORF1ab), ORF3a, and ORF6, respectively. Dog and cat SARS-CoV-2 isolates showed one and seven unique amino acid substitutions in ORF1ab, respectively. Further studies may be necessary to determine the pathogenic significance of these amino acid substitutions to understand the molecular epidemiology and evolution of SARS-CoV-2.

Recombinant Variants of Tissue-Type Plasminogen Activator Containing Amino Acid Substitutions in the Finger Domain

1992 ◽  
Vol 68 (06) ◽  
pp. 672-677 ◽  
Author(s):  
Hitoshi Yahara ◽  
Keiji Matsumoto ◽  
Hiroyuki Maruyama ◽  
Tetsuya Nagaoka ◽  
Yasuhiro Ikenaka ◽  
...  
Keyword(s):  
Amino Acid ◽  
Plasminogen Activator ◽  
Half Life ◽  
Tissue Type ◽  
Clot Lysis ◽  
Amino Acid Substitutions ◽  
Wild Type ◽  
Plasma Clot ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator

SummaryTissue-type plasminogen activator (t-PA) is a fibrin-specific agent which has been used to treat acute myocardial infarction. In an attempt to clarify the determinants for its rapid clearance in vivo and high affinity for fibrin clots, we produced five variants containing amino acid substitutions in the finger domain, at amino acid residues 7–9, 10–14, 15–19, 28–33, and 37–42. All the variants had a prolonged half-life and a decreased affinity for fibrin of various degrees. The 37–42 variant demonstrated about a 6-fold longer half-life with a lower affinity for fibrin. Human plasma clot lysis assay estimated the fibrinolytic activity of the 37–42 variant to be 1.4-fold less effective than that of the wild-type rt-PA. In a rabbit jugular vein clot lysis model, doses of 1.0 and 0.15 mg/kg were required for about 70% lysis in the wild-type and 37–42 variant, respectively. Fibrinogen was degraded only when the wild-type rt-PA was administered at a dose of 1.0 mg/kg. These findings suggest that the 37–42 variant can be employed at a lower dosage and that it is a more fibrin-specific thrombolytic agent than the wild-type rt-PA.

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