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Master's Dissertation
DOI
https://doi.org/10.11606/D.59.2021.tde-24082021-145318
Document
Author
Full name
Patrícia Pereira Duzi Carvalho
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2020
Supervisor
Committee
Alves, Nelson Augusto (President)
Oliveira, Ronaldo Junio de
Silva, Fernando Luis Barroso da
Title in Portuguese
Caracterização da interação dos coronavírus SARS-CoV e SARS-CoV-2 com o receptor ACE2 por meio de um padrão evolutivo conservado de aminoácidos
Keywords in Portuguese
1. ACE2
2. SARS-CoV-2
3. SARS-CoV
4. COVID-19
5. Conservação de aminoácidos
6. Bolso hidrofóbico
7. Bioinformática.
Abstract in Portuguese
As proteínas spike (S) medeiam a entrada do coronavírus na célula hospedeira. A subunidade S1 das proteínas S contém o domínio de ligação ao receptor (RBD) que é capaz de reconhecer diferentes receptores, destacando sua notável capacidade de adaptação aos seus hospedeiros ao longo da evolução viral. Enquanto o RBD situado na proteína spike e determinante para a interação vírus-receptor, os resíduos ativos estão no motivo de ligação ao receptor (RBM), uma região localizada no RBD que desempenha um papel fundamental na ligação da superfície externa de seus receptores. Neste projeto de pesquisa, abordamos a hipótese de que as cepas dos coronavírus SARS-CoV e SARS-CoV-2 capazes de usar a enzima conversora de angiotensina 2 (ACE2) para infectar células hospedeiras adaptaram seu RBM ao longo da evolução viral para explorar topologias conformacionais direcionadas pelos resíduos de aminoácidos YGF que formam um bolso hidrofóbico, importante via de reconhecimento e ligação ao receptor. Mecanismo similar e usado na interação do complexo UBA-ubiquitina, associado a proteólise. Utilizamos neste projeto diferentes gêneros de coronavírus e suas sequências foram analisadas com ClustalW e Jalview com o intuito de investigar se o mecanismo molecular baseado em YGF pode atuar como uma assinatura proteica localizada no RBM, distinguindo os coronavírus capazes de usar o ACE2 como um receptor de entrada celular. Os resíduos analisados podem representar um alvo importante para o desenvolvimento de medicamentos e além disso, a compreensão da organização do coronavírus na ligação ao receptor ACE2.
Title in English
Featuring ACE2 binding SARS-CoV and SARS-CoV-2 through a conserved evolutionary pattern of amino acid residues
Keywords in English
ACE2
Conservation of amino acids
hydrophobic pocket.
SARS-CoV-2
SARS-CoV. COVID-19
Abstract in English
Spike (S) proteins mediate coronavirus entry into the host cell. The S1 subunit of the S proteins contains the receptor-binding domain (RBD) that is able to recognize different host receptors, highlighting its remarkable capacity to adapt to their hosts along the viral evolution. While RBD in spike proteins is determinant for the virus-receptor interaction, the active residues lie at the receptor-binding motif (RBM), a region located in RBD that plays a fundamental role binding the outer surface of their receptors. In this research project, we approached the hypothesis that strains of the SARS-CoV and SARS-CoV-2 coronaviruses capable of using the angiotensin-converting enzyme 2 (ACE2) to infect host cells adapted their RBM throughout viral evolution to explore topologies conformational directed by the YGF amino acid residues that form a hydrophobic pocket, an important pathway for recognition and binding to the receptor. A similar mechanism is used in the interaction of the UBA-ubiquitin complex, associated with proteolysis. In this project we used different genera of coronaviruses and their sequences were analyzed with ClustalW and Jalview in order to investigate whether the molecular mechanism based on YGF can act as a protein signature located in the RBM, distinguishing coronaviruses capable of using ACE2 as a receptor for cell entry. The analyzed residues may represent an important target for the development of medications and in addition, the understanding of the organization of the coronavirus in the binding to the ACE2 receptor.
 
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Release Date
2023-05-06
Publishing Date
2021-11-22
 
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