Carbohydrates in the interaction of SARS Cov2 B.1.617.2 (Delta) with ACE2
Abstract: Allergic patients, particularly those suffering from asthma, have focused attention due to the frequency with which they present respiratory symptoms that could make them highly vulnerable to Covid 19. It is also discussed whether their predisposition to trigger an IgE-media...
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| Formato: | Artículo revista |
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Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
2022
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| Acceso en línea: | https://revistas.unc.edu.ar/index.php/med/article/view/34845 |
| Aporte de: |
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I10-R327-article-34845 |
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ojs |
| institution |
Universidad Nacional de Córdoba |
| institution_str |
I-10 |
| repository_str |
R-327 |
| container_title_str |
Revista de la Facultad de Ciencias Médicas de Córdoba |
| format |
Artículo revista |
| topic |
SARS Cov2 RBD S protein affinity in sílico SARS Cov2 RBD proteína S afinidad in sílico . |
| spellingShingle |
SARS Cov2 RBD S protein affinity in sílico SARS Cov2 RBD proteína S afinidad in sílico . Cossy Isasi , S Muiño , JC Carbohydrates in the interaction of SARS Cov2 B.1.617.2 (Delta) with ACE2 |
| topic_facet |
SARS Cov2 RBD S protein affinity in sílico SARS Cov2 RBD proteína S afinidad in sílico . |
| author |
Cossy Isasi , S Muiño , JC |
| author_facet |
Cossy Isasi , S Muiño , JC |
| author_sort |
Cossy Isasi , S |
| title |
Carbohydrates in the interaction of SARS Cov2 B.1.617.2 (Delta) with ACE2 |
| title_short |
Carbohydrates in the interaction of SARS Cov2 B.1.617.2 (Delta) with ACE2 |
| title_full |
Carbohydrates in the interaction of SARS Cov2 B.1.617.2 (Delta) with ACE2 |
| title_fullStr |
Carbohydrates in the interaction of SARS Cov2 B.1.617.2 (Delta) with ACE2 |
| title_full_unstemmed |
Carbohydrates in the interaction of SARS Cov2 B.1.617.2 (Delta) with ACE2 |
| title_sort |
carbohydrates in the interaction of sars cov2 b.1.617.2 (delta) with ace2 |
| description |
Abstract:
Allergic patients, particularly those suffering from asthma, have focused attention due to the frequency with which they present respiratory symptoms that could make them highly vulnerable to Covid 19. It is also discussed whether their predisposition to trigger an IgE-mediated response could be protective against the entrance of the virus or it would only increase morbidity. Currently, variant B.1.617.2 (Delta strain)affects our population, whose greater transmissibility might be due to mutations that reduce its affinity for ACE2, also giving it the ability to evade binding with neutralizing immunoglobulins (Ig). The affinity of S protein has been studied considering only the primary, secondary and tertiary structures of ligand and receptor. On this occasion, we present an in silico exploration of the influence of some oligosaccharides common in biological structures on the affinity of S protein of the B.1.617.2 (Delta) variant compared to the original (GenBank MN908947, Wt).
The simulations of binding interactions between S protein´s receptor-binding domain (RBD) and ACE2 (RBD binding domain) were done with EADock, Autodock Vina, Chimera, widely accepted open source software. The structures of the proteins and oligosaccharides obtained by X-ray diffraction and electron microscopy were downloaded from RCSB-PDB and edited to reduce the volume of data according to the available hardware and software.
The affinities obtained (binding deltaG) were: for RBD-ACE2 -4.6: 0.0 kcal / mol and for oligosaccharide binding, galactose -6.1: -5.2; glucosyl galactosyl glucosaminyl galactosaminyl sialic -5.9: -4.8 ,; glucosyl galactosyl glucosaminyl galactosaminyl disialic -7.53: -5.5 kcal / mol Wt : Delta variant respectively.
The results are preliminary but are consistent with recent literature that is based on structural studies, not on receptor-ligand binding analyses. The results indicate that RBD Wt has affinity for deglycosylated ACE2 while the Delta variant does not. The Delta variant would present a lower affinity for carbohydrates. In summary, the affinity (protein-protein) and avidity (RBD-carbohydrates) would be lower in the Delta variant, favoring its permanence in extracellular fluids and attenuating the aggressiveness of the onset of infection.
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| publisher |
Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología |
| publishDate |
2022 |
| url |
https://revistas.unc.edu.ar/index.php/med/article/view/34845 |
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2024-09-03T21:02:39Z |
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2024-09-03T21:02:39Z |
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I10-R327-article-348452024-04-15T16:19:09Z Carbohydrates in the interaction of SARS Cov2 B.1.617.2 (Delta) with ACE2 Glúcidos en la interacción SARS Cov2 B.1.617.2 (delta) con ACE2 A Cossy Isasi , S Muiño , JC SARS Cov2 RBD S protein affinity in sílico SARS Cov2 RBD proteína S afinidad in sílico . Abstract: Allergic patients, particularly those suffering from asthma, have focused attention due to the frequency with which they present respiratory symptoms that could make them highly vulnerable to Covid 19. It is also discussed whether their predisposition to trigger an IgE-mediated response could be protective against the entrance of the virus or it would only increase morbidity. Currently, variant B.1.617.2 (Delta strain)affects our population, whose greater transmissibility might be due to mutations that reduce its affinity for ACE2, also giving it the ability to evade binding with neutralizing immunoglobulins (Ig). The affinity of S protein has been studied considering only the primary, secondary and tertiary structures of ligand and receptor. On this occasion, we present an in silico exploration of the influence of some oligosaccharides common in biological structures on the affinity of S protein of the B.1.617.2 (Delta) variant compared to the original (GenBank MN908947, Wt). The simulations of binding interactions between S protein´s receptor-binding domain (RBD) and ACE2 (RBD binding domain) were done with EADock, Autodock Vina, Chimera, widely accepted open source software. The structures of the proteins and oligosaccharides obtained by X-ray diffraction and electron microscopy were downloaded from RCSB-PDB and edited to reduce the volume of data according to the available hardware and software. The affinities obtained (binding deltaG) were: for RBD-ACE2 -4.6: 0.0 kcal / mol and for oligosaccharide binding, galactose -6.1: -5.2; glucosyl galactosyl glucosaminyl galactosaminyl sialic -5.9: -4.8 ,; glucosyl galactosyl glucosaminyl galactosaminyl disialic -7.53: -5.5 kcal / mol Wt : Delta variant respectively. The results are preliminary but are consistent with recent literature that is based on structural studies, not on receptor-ligand binding analyses. The results indicate that RBD Wt has affinity for deglycosylated ACE2 while the Delta variant does not. The Delta variant would present a lower affinity for carbohydrates. In summary, the affinity (protein-protein) and avidity (RBD-carbohydrates) would be lower in the Delta variant, favoring its permanence in extracellular fluids and attenuating the aggressiveness of the onset of infection. Resumen: Los pacientes alérgicos, particularmente los que sufren asma, han concentrado atención debido a la frecuencia con que presentan síntomas respiratorios que podrían hacerlos altamente vulnerables ante Covid 19. Se discute además si su predisposición a desencadenar una respuesta mediada por IgE podría ser protectora frente al ingreso del virus o solamente aumentaría la morbilidad. Actualmente impacta en nuestra población la variante B.1.617.2 o cepa d cuya mayor transmisibilidad se debería a mutaciones que reducen su afinidad por ACE2, dándole capacidad de evadir la unión con inmunogloblinas (Igs) neutralizantes. La afinidad de la proteína S se ha estudiado considerando sólo las estructuras primaria, secundaria y terciaria de ligando y receptor. Se presenta en esta ocasión una exploración in sílico de la influencia de algunos oligosacáridos frecuentes en estructuras biológicas sobre la afinidad de la proteína S de la variante B.1.617.2 comparada con la original (GenBank MN908947). Las simulaciones de unión de la proteína S dominio de unión al receptor (RBD) y ACE2 (dominio de unión a RBD) se hicieron con EADock, Autodock Vina, Chimera, software open source ampliamente consensuado. Las estructuras de las proteínas y oligosacáridos obtenidas por difracción de rayos X y microscopía electrónica de RCSB-PDB se descargaron y editaron para reducir el volumen de datos acorde al hardware y software disponible. Las afinidades obtenidas (deltaG de unión) fueron: para la RBD-ACE2 de -4,6 : 0,0 kcal/mol y para la unión de oligosacáridos, galactosa -6,1 : -5,2 ; glucosil galactosil glucosaminil glactosaminil siálico -5,9 : -4,8,; glucosil galactosil glucosaminil glactosaminil disiálico -7,53 : -5,5 kcal/mol Wt : Variante Delta respectivamente. Los resultados son preliminares pero están en consonancia con bibliografía reciente que se basa en estudios estructurales, no de unión ligando receptor. Los resultados indican que RBD Wt tiene afinidad por ACE2 deglicosilada mientras que la variante Delta no. La variante Delta presentaría menor afinidad por glúcidos. En resumen, la afinidad (proteína-proteína) y la avidez (RBD-glúcidos) serían menores en la variante Delta favoreciendo su permanencia en fluídos extracelulares y atenuando la agresividad del inicio de la infección. . Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2022-06-07 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion texto texto texto https://revistas.unc.edu.ar/index.php/med/article/view/34845 Revista de la Facultad de Ciencias Médicas de Córdoba.; Vol. 78 No. Suplemento (2021): Suplemento JIC XXII Revista de la Facultad de Ciencias Médicas de Córdoba; Vol. 78 Núm. Suplemento (2021): Suplemento JIC XXII Revista da Faculdade de Ciências Médicas de Córdoba; v. 78 n. Suplemento (2021): Suplemento JIC XXII 1853-0605 0014-6722 http://creativecommons.org/licenses/by-nc/4.0 |