Tuesday, 27 February 2024 09:38

Identifican mutaciones que afectan la multiplicación del virus SARS-CoV-2 con redes neuronales

Mapas neuronales como el dibujado en el centro han servido para identificar mutaciones que afectan a la polimerasa del virus del SARS-CoV-2. La imagen transmite la multidisciplinariedad del estudio y la gran diversidad que se está descubriendo para este virus. Mapas neuronales como el dibujado en el centro han servido para identificar mutaciones que afectan a la polimerasa del virus del SARS-CoV-2. La imagen transmite la multidisciplinariedad del estudio y la gran diversidad que se está descubriendo para este virus. Soledad Delgado, Pilar Somovilla y Javier Muñoz.
  • El estudio ha revelado la aparición incipiente de variantes de coronavirus con propiedades biológicas alteradas en pacientes de COVID-19
  • Estas mutaciones, hasta ahora inadvertidas por su baja proporción en los pacientes infectados, han sido detectadas gracias a una técnica de secuenciación ultra-profunda

Equipos del Consejo Superior de Investigaciones Científicas (CSIC), de la Universidad Politécnica de Madrid y de la Fundación Jiménez Díaz han revelado en pacientes de COVID-19 la aparición incipiente de variantes de coronavirus con propiedades biológicas alteradas.

El estudio utilizó muestras de virus aislados de pacientes de la primera ola de COVID-19 en Madrid, sobre las que se aplica una técnica de secuenciación ultra-profunda para identificar mutaciones presentes en muy baja proporción. En cada paciente infectado se hallaron multitud de mutaciones cuya relación de parentesco se analizó mediante mapas de redes neuronales. Este procedimiento, basado en técnicas de computación avanzada, permite visualizar en forma de mapas tridimensionales las secuencias con distintas mutaciones, la distancia evolutiva entre secuencias y la frecuencia con la que se encuentran en cada paciente.

El foco se fijó sobre la proteína que permite la multiplicación del virus, llamada polimerasa, y en la proteína responsable de inducir la producción de anticuerpos que pueden proteger frente a enfermedad grave. La investigación ha demostrado que algunas de las mutaciones son capaces de modificar la velocidad con la que se multiplica el virus. Para confirmar este efecto, se purificó la polimerasa del virus y se comprobó que su capacidad de copiar el material genético del virus varía considerablemente entre las polimerasas mutantes que de modo incipiente surgen en los virus de los pacientes. Estas mutaciones hasta ahora habían pasado inadvertidas por su baja proporción en los pacientes infectados.

El estudio ha sido codirigido por Soledad Delgado, Celia Perales, Nuria Verdaguer y Esteban Domingo, en el consorcio participan también investigadores de la Universidad Complutense de Madrid, la Northwestern University de Estados Unidos y la consultora internacional Management Solutions. Su éxito se ha basado en el marcado carácter interdisciplinar de la investigación, en la que se han aunado un amplio abanico de conocimientos que abarcan desde la medicina a la biología estructural y la bioinformática.

Los resultados han puesto de manifiesto que la capacidad de variación de este coronavirus es mucho mayor de lo que se sospechaba, con una rápida proliferación de mutantes de comportamiento distinto. Ello obliga a buscar tratamientos más eficaces, que es uno de los objetivos que tiene planteados actualmente el consorcio.

El trabajo acaba de ser publicado en la revista PNAS de la Academia Nacional de Ciencias de los Estados Unidos.

Firma: CSIC Comunicación / CBM Comunicación

Referencia bibliográfica: S Delgado, P Somovilla, C Ferrer-Orta, B Martínez-González, S Vázquez-Monteagudo, J Muñoz-Flores, ME Soria, C García-Crespo, AI de Avila, A Duran-Pastor, I Gadea, C López-Galíndez, F Morán, R Lorenzo-Redondo, N Verdaguer, C Perales, and E Domingo. (2024). Incipient functional SARS-CoV-2 diversification identified through neural network haplotype maps. Proceedings of the National Academy of Sciences of the United States of America.

DOI: 10.1073/pnas.2317851121 www.pnas.org/doi/10.1073/pnas.2317851121

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