{"id":279968,"date":"2024-07-31T09:00:21","date_gmt":"2024-07-31T07:00:21","guid":{"rendered":"https:\/\/dhcp205002.cbm.uam.es\/?page_id=279968"},"modified":"2026-01-23T09:23:27","modified_gmt":"2026-01-23T08:23:27","slug":"variabilidad-genetica-de-virus-rna","status":"publish","type":"page","link":"https:\/\/www.cbm.uam.es\/index.php\/programas-cientificos\/interacciones-con-el-entorno\/microorganismos-en-la-salud-y-el-bienestar\/variabilidad-genetica-de-virus-rna\/?lang=es","title":{"rendered":"Variabilidad gen\u00e9tica de virus RNA"},"content":{"rendered":"

[et_pb_section fb_built=”1″ _builder_version=”4.27.0″ _module_preset=”default” background_color=”#34609B” background_image=”https:\/\/www.cbm.uam.es\/wp-content\/uploads\/2024\/07\/iStock-1833377669small-scaled.jpg” background_position=”bottom_center” background_vertical_offset=”32%” min_height=”352px” height=”294px” da_disable_devices=”off|off|off” global_colors_info=”{}” da_is_popup=”off” da_exit_intent=”off” da_has_close=”on” da_alt_close=”off” da_dark_close=”off” da_not_modal=”on” da_is_singular=”off” da_with_loader=”off” da_has_shadow=”on”][et_pb_row column_structure=”2_5,3_5″ use_custom_gutter=”on” gutter_width=”4″ _builder_version=”4.23.4″ _module_preset=”default” background_color=”RGBA(255,255,255,0)” custom_margin=”61px||||false|false” custom_padding=”||0px|||” global_colors_info=”{}”][et_pb_column type=”2_5″ _builder_version=”4.23.4″ _module_preset=”default” background_color=”rgba(52,96,155,0.83)” custom_padding=”50px||50px|50px|false|false” border_radii=”on|15px|15px|15px|15px” global_colors_info=”{}”][et_pb_text _builder_version=”4.25.0″ _module_preset=”default” text_text_color=”#FFFFFF” custom_margin=”0px||10px||false|false” custom_padding=”0px||0px||false|false” global_colors_info=”{}”]<\/p>\n

Programa Cient\u00edfico<\/p>\n

[\/et_pb_text][et_pb_heading title=”Interacciones con el entorno” _builder_version=”4.25.0″ _module_preset=”default” title_font=”Montserrat||||||||” title_text_color=”#FFFFFF” title_font_size=”43px” global_colors_info=”{}”][\/et_pb_heading][\/et_pb_column][et_pb_column type=”3_5″ _builder_version=”4.23.4″ _module_preset=”default” custom_padding=”157px||||false|false” global_colors_info=”{}”][et_pb_text _builder_version=”4.25.0″ _module_preset=”default” global_colors_info=”{}”]<\/p>\n

UNIDADES EN ESTE PROGRAMA
\n<\/span><\/h4>\n
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\nMicroorganismos en la salud y el bienestar<\/a><\/span> Desarrollo y funci\u00f3n del sistema inmunitario<\/a><\/span> <\/h6>\n

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\nORCID<\/a><\/p>\n

[\/et_pb_text][\/et_pb_column][et_pb_column type=”1_4″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_image src=”\/imgs\/226.jpg” title_text=”logoRecurso 7″ align=”right” module_class=”roundedImg” _builder_version=”4.27.5″ _module_preset=”default” global_colors_info=”{}”][\/et_pb_image][\/et_pb_column][et_pb_column type=”1_4″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_heading title=”Celia Perales Viejo” _builder_version=”4.27.5″ _module_preset=”default” title_level=”h3″ title_text_align=”left” title_text_color=”#008C93″ global_colors_info=”{}”][\/et_pb_heading][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”4.23.4″ _module_preset=”default” background_color=”#13B5BD” custom_margin=”0px||0px||false|false” custom_padding=”0px||0px||false|false” da_disable_devices=”off|off|off” global_colors_info=”{}” da_is_popup=”off” da_exit_intent=”off” da_has_close=”on” da_alt_close=”off” da_dark_close=”off” da_not_modal=”on” da_is_singular=”off” da_with_loader=”off” da_has_shadow=”on”][et_pb_row column_structure=”1_3,1_3,1_3″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_column type=”1_3″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_button button_url=”#investiga” button_text=”Investigaci\u00f3n” button_alignment=”center” _builder_version=”4.25.0″ _module_preset=”default” custom_button=”on” button_bg_color=”#34609B” animation_style=”zoom” global_colors_info=”{}”][\/et_pb_button][\/et_pb_column][et_pb_column type=”1_3″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_button button_url=”#personal” button_text=”Miembros del grupo” button_alignment=”center” _builder_version=”4.25.0″ _module_preset=”default” custom_button=”on” button_bg_color=”#34609B” custom_padding=”|44px||44px|false|true” animation_style=”zoom” global_colors_info=”{}”][\/et_pb_button][\/et_pb_column][et_pb_column type=”1_3″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_button button_url=”#publica” button_text=”Publicaciones” button_alignment=”center” _builder_version=”4.25.0″ _module_preset=”default” custom_button=”on” button_bg_color=”#34609B” animation_style=”zoom” global_colors_info=”{}”][\/et_pb_button][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”4.23.4″ _module_preset=”default” background_enable_image=”off” background_size=”custom” background_image_height=”84%” background_position=”bottom_right” custom_margin=”0px||0px||false|false” custom_padding=”0px||15px||false|false” da_disable_devices=”off|off|off” global_colors_info=”{}” da_is_popup=”off” da_exit_intent=”off” da_has_close=”on” da_alt_close=”off” da_dark_close=”off” da_not_modal=”on” da_is_singular=”off” da_with_loader=”off” da_has_shadow=”on”][et_pb_row column_structure=”1_2,1_2″ use_custom_gutter=”on” gutter_width=”2″ _builder_version=”4.23.4″ _module_preset=”default” custom_margin=”20px||||false|false” custom_padding=”||||false|false” global_colors_info=”{}”][et_pb_column type=”1_2″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_text admin_label=”resumen” module_id=”resumen” module_class=”resumen” _builder_version=”4.25.0″ _module_preset=”default” text_font_size=”15px” text_line_height=”1.8em” background_color=”#f1f8fe” custom_padding=”20px|20px|20px|20px|true|false” border_width_top=”1px” border_color_top=”#008C93″ border_width_bottom=”1px” border_color_bottom=”#008C93″ global_colors_info=”{}”]<\/p>\n

La variabilidad gen\u00e9tica de virus RNA es un paradigma de complejidad biol\u00f3gica, con implicaciones te\u00f3ricas y pr\u00e1cticas. Es una dificultad importante para el control de enfermedades. Investigamos la complejidad de SARS-CoV-2 mediante herramientas experimentales y de computaci\u00f3n avanzada. Buscamos tratamientos antiv\u00edricos basados en mutag\u00e9nesis letal que inhiban eficazmente la replicaci\u00f3n viral. <\/p>\n

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Nuestro trabajo previo con los virus RNA pat\u00f3genos, el virus de la fiebre aftosa, el virus de la inmunodeficiencia humana tipo 1, el virus de la coriomeningitis linfocitaria de rat\u00f3n y el virus de la hepatitis C (VHC), proporcion\u00f3 una imagen unificada de las implicaciones que tiene que las poblaciones de virus consistan en nubes de mutantes. Estos primeros estudios abrieron el camino a la mutag\u00e9nesis letal (extinci\u00f3n de virus por exceso de mutaciones) como estrategia antiviral eficaz que hemos investigado con varios virus. Algunos de los agentes antivirales utilizados actualmente y aprobados para su uso en terapia antiviral humana act\u00faan mediante mutag\u00e9nesis letal. Se logr\u00f3 un avance significativo cuando documentamos que dos an\u00e1logos de nucle\u00f3sido ejerc\u00edan una actividad anti-VHC sin\u00e9rgica, abriendo as\u00ed el camino a tratamientos mejorados que requieren dosis m\u00e1s bajas de f\u00e1rmacos. Recientemente, hemos demostrado que la mutag\u00e9nesis letal sin\u00e9rgica es eficaz para extinguir el SARS-CoV-2. <\/p>\n

[\/et_pb_text][\/et_pb_column][et_pb_column type=”2_5″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_image src=”https:\/\/www.cbm.uam.es\/wp-content\/uploads\/2024\/12\/2023-02-15-Grupo-Esteban-Domingo-05-1000px.jpg” title_text=”2023-02-15 Grupo Esteban Domingo 05-1000px” _builder_version=”4.27.3″ _module_preset=”default” custom_margin=”60px||||false|false” custom_padding=”|||27px||” animation_style=”zoom” border_width_all=”3px” border_color_all=”#13B5BD” box_shadow_style=”preset3″ global_colors_info=”{}”][\/et_pb_image][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=”4.23.4″ _module_preset=”default” custom_padding=”0px||||false|false” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_text _builder_version=”4.25.0″ _module_preset=”default” global_colors_info=”{}”]<\/p>\n

The emergence of COVID-19 and its causative agent, SARS-CoV-2, posed a double scientific challenge, that we are currently approaching in collaboration with the group of Dr. Celia Perales (CNB-CSIC). The first challenge was to explore whether this new pathogen adhered to the tenets of quasispecies dynamics that we had established for other viruses. Given the large coronavirus genome size, and its encoding an exonuclease proofreading-repair enzyme, many experts believed (and some still do) that the degree of intra-host diversity of this virus would be limited, and so would be the impact of quasispecies dynamics in its behavior and disease treatment protocols. This first challenge has been largely solved by collaborative work of our two teams with a multidisciplinary consortium that includes M.Ds and Ph.Ds from Fundaci\u00f3n Jim\u00e9nez-D\u00edaz, Dr. Soledad Delgado (UPM) (assisted by Dr. Federico Mor\u00e1n of UCM and Cecilio L\u00f3pez-Gal\u00edndez of ISCIII), the group of Dr. Nuria Verdaguer (IBMB-CSIC), Dr. Ram\u00f3n Lorenzo-Redondo (Northwestern University, USA) and the consulting international company Management Solutions. We have quantified an extensive SARS-CoV-2 population heterogeneity within infected COVID-19 patients by reaching by ultra-deep sequencing an unprecedented resolution of minority mutations, present at 0.1% frequency. Significantly, by studying multiple haplotypes within patients using self-organized neuronal maps, we have shown that the incipient diversification observed in infected individuals is functionally relevant. Indeed, several mutations that arise within infected patients changed the kinetics of viral RNA synthesis.
The second challenge was if variation of SARS-CoV-2 was sufficient to pose a difficulty for COVID-19 control and, therefore, if our synergistic lethal mutagenesis approach would be useful as an antiviral design. Again, quasispecies dynamics of SARS-CoV-2 had the expected consequences: vaccines exhibit limited effectiveness, and they require periodic updating. Likewise, synergistic antiviral treatments will be required to reach adequate efficacy, and to minimize selection of antiviral-resistant mutants.
Use of neuronal networks to understand the informational contents and implications of SARS-CoV-2 mutant clouds, and the search of new antiviral combinations based on lethal mutagenesis, are the two major research lines of our laboratory. To achieve these aims we have available thousands of SARS-CoV-2 isolates from patients of the different COVID-19 waves, who display different clinical profiles (immunocompetent, immunocompromised, etc.). Also, with the support of the group of Dr. Luis Enjuanes (CNB-CSIC) we have developed a cell culture system to study SARS-CoV-2 population dynamics, and protocols to obtain virus of different replicative fitness in a cell culture environment. Since fitness is by itself a factor of antiviral resistance, the availability of high fitness SARS-CoV-2 will permit applying stricter protocols of antiviral efficacy than using standard virus isolates. <\/p>\n

[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”4.23.4″ _module_preset=”default” background_color=”rgba(0,0,0,0.04)” da_disable_devices=”off|off|off” global_colors_info=”{}” da_is_popup=”off” da_exit_intent=”off” da_has_close=”on” da_alt_close=”off” da_dark_close=”off” da_not_modal=”on” da_is_singular=”off” da_with_loader=”off” da_has_shadow=”on”][et_pb_row _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_heading title=”Miembros del grupo” module_id=”personal” _builder_version=”4.25.0″ _module_preset=”default” custom_margin=”0px|||0px|false|false” custom_padding=”3px|||8px|false|false” border_width_left=”6px” border_color_left=”#34609B” global_colors_info=”{}”][\/et_pb_heading][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=”4.25.0″ _module_preset=”default” max_width=”2560px” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.25.0″ _module_preset=”default” global_colors_info=”{}”][et_pb_code _builder_version=”4.25.2″ _module_preset=”default” global_colors_info=”{}”][et_pb_row _builder_version=\"4.25.0\" _module_preset=\"default\" column_structure=\"1_4,1_4,1_4,1_4\" hover_enabled=\"0\" sticky_enabled=\"0\"][et_pb_column _builder_version=\"4.25.0\" _module_preset=\"default\" type=\"1_4\"][et_pb_blurb title=\"Esteban Domingo Sol\u00e1ns\" image=\"\/imgs\/45.jpg\" _builder_version=\"4.25.0\" _module_preset=\"default\" header_text_align=\"center\" body_text_align=\"center\" global_colors_info=\"{}\" theme_builder_area=\"post_content\" module_class=\"roundedImg\"]

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Exploration of sequence space as the basis of viral RNA genome segmentation<\/h3>\n

Elena Moreno et al.<\/p>\n

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Synergistic Lethal Mutagenesis of Hepatitis C Virus<\/h3>\n

Isabel Gallego et al.<\/p>\n

[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”1_4,1_4,1_4,1_4″ _builder_version=”4.23.4″ _module_preset=”default” animation_style=”zoom” global_colors_info=”{}”][et_pb_column type=”1_4″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_image src=”https:\/\/www.cbm.uam.es\/wp-content\/uploads\/2024\/09\/Selected-publication_3_Web_ED_2022.jpg” title_text=”Imagen sobre la publicaci\u00f3n” url_new_window=”on” _builder_version=”4.27.0″ _module_preset=”default” global_colors_info=”{}”][\/et_pb_image][\/et_pb_column][et_pb_column type=”1_4″ _builder_version=”4.25.0″ _module_preset=”default” global_colors_info=”{}”][et_pb_text _builder_version=”4.25.0″ _module_preset=”default” link_option_url=”https:\/\/www.mdpi.com\/2076-0817\/11\/6\/662″ link_option_url_new_window=”on” global_colors_info=”{}”]<\/p>\n

SARS-CoV-2 Mutant Spectra at Different Depth Levels Reveal an Overwhelming Abundance of Low Frequency Mutations<\/h3>\n

Brenda Mart\u00ednez-Gonz\u00e1lez et al.<\/p>\n

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Incipient functional SARS-CoV-2 diversification identified through neural network haplotype maps<\/h3>\n

Soledad Delgado et al.<\/p>\n

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