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Unraveling the molecular basis of host cell receptor usage in SARS-CoV-2 and other human pathogenic ß-CoVs.
Pontes, Camila; Ruiz-Serra, Victoria; Lepore, Rosalba; Valencia, Alfonso.
  • Pontes C; Barcelona Supercomputing Center (BSC), 08034 Barcelona, Spain.
  • Ruiz-Serra V; University of Brasília (UnB), 70910-900, Brasília - DF, Brazil.
  • Lepore R; Barcelona Supercomputing Center (BSC), 08034 Barcelona, Spain.
  • Valencia A; Barcelona Supercomputing Center (BSC), 08034 Barcelona, Spain.
Comput Struct Biotechnol J ; 19: 759-766, 2021.
Article in English | MEDLINE | ID: covidwho-1036889
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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Semantic information from SemMedBD (by NLM)
1. Basis TREATS Betacoronavirus
Subject
Basis
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TREATS
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Betacoronavirus
2. Basis TREATS 2019 novel coronavirus
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Basis
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2019 novel coronavirus
3. 2019 novel coronavirus PROCESS_OF human group
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2019 novel coronavirus
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4. M Protei PART_OF C2806453
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M Protei
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C2806453
5. receptor INTERACTS_WITH ACE2 gene|ACE2
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receptor
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INTERACTS_WITH
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6. Basis TREATS Betacoronavirus
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Basis
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TREATS
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Betacoronavirus
7. Basis TREATS 2019 novel coronavirus
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Basis
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TREATS
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2019 novel coronavirus
8. 2019 novel coronavirus PROCESS_OF human group
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2019 novel coronavirus
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PROCESS_OF
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human group
9. M Protein, multiple myeloma PART_OF Betacoronavirus
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M Protein, multiple myeloma
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PART_OF
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Betacoronavirus
10. receptor INTERACTS_WITH ACE2 gene|ACE2
Subject
receptor
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INTERACTS_WITH
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ACE2 gene|ACE2
ABSTRACT
The recent emergence of the novel SARS-CoV-2 in China and its rapid spread in the human population has led to a public health crisis worldwide. Like in SARS-CoV, horseshoe bats currently represent the most likely candidate animal source for SARS-CoV-2. Yet, the specific mechanisms of cross-species transmission and adaptation to the human host remain unknown. Here we show that the unsupervised analysis of conservation patterns across the ß-CoV spike protein family, using sequence information alone, can provide valuable insights on the molecular basis of the specificity of ß-CoVs to different host cell receptors. More precisely, our results indicate that host cell receptor usage is encoded in the amino acid sequences of different CoV spike proteins in the form of a set of specificity determining positions (SDPs). Furthermore, by integrating structural data, in silico mutagenesis and coevolution analysis we could elucidate the role of SDPs in mediating ACE2 binding across the Sarbecovirus lineage, either by engaging the receptor through direct intermolecular interactions or by affecting the local environment of the receptor binding motif. Finally, by the analysis of coevolving mutations across a paired MSA we were able to identify key intermolecular contacts occurring at the spike-ACE2 interface. These results show that effective mining of the evolutionary records held in the sequence of the spike protein family can help tracing the molecular mechanisms behind the evolution and host-receptor adaptation of circulating and future novel ß-CoVs.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Type of study: Randomized controlled trials Language: English Journal: Comput Struct Biotechnol J Year: 2021 Document Type: Article Affiliation country: J.csbj.2021.01.006

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Randomized controlled trials Language: English Journal: Comput Struct Biotechnol J Year: 2021 Document Type: Article Affiliation country: J.csbj.2021.01.006