Drug repurposing to find inhibitors of SARS-CoV-2 main protease

Autores
Conti, German Andres; Gómez Chávez, José Leonardo; Angelina, Emilio Luis; Peruchena, Nelida Maria
Año de publicación
2021
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the strain of coronavirus that causes coronavirus disease 2019 (COVID-19), the respiratory illness responsible for the COVID-19 pandemic. As of October 2021, with about 6 billion doses of COVID-19 vaccines administered globally, the world is slowly returning back to normality. However, there is still a need for novel therapeutics for people that contracted the disease either because they were not vaccinated or because the vaccine was not effective for them. Drug repurposing is a strategy for identifying new uses for approved drugs that has the advantage, over conventional approaches that attempt to develop a drug from scratch, that the time frame of the overall process can be significantly reduced because of the few number of clinical trials required. In this work, a structure-based virtual screening of FDA-approved drugs was performed for repositioning as potential inhibitors of the main protease Mpro of SARS-CoV-2. 12 drugs were prioritized from the Virtual Screening campaigns as potential inhibitors of the Mpro enzyme. Some of the selected compounds turned out to be antiviral drugs already being tested in COVID-19 clinical trials or used to alleviate symptoms of the disease. Curiously, the most promising candidate is the naturally occurring broad spectrum antibiotic Oxytetracycline (OTC). This drug has largely outperformed the remaining selected candidates along all filtering steps of the virtual screening workflow. The closely related tetracycline-derived drug Doxycycline (DOX) recently has proven to reduce the viral load in Vero cells infected with SARS-CoV-2. Since OTC but not DOX surpassed the more stringent filters in the late stages of our virtual screening pipeline, we suspect that OTC will show even higher antiviral activity than DOX in viral replication experiments.Considering our computational findings together with the proven antiviral properties of DOX, we believe it is worth testing OTC in prospective viral replication studies. We encourage the scientific community working on COVID-19 projects to include this repurposing candidate on their experimental screening pipelines.
Fil: Conti, German Andres. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina
Fil: Gómez Chávez, José Leonardo. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Angelina, Emilio Luis. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Peruchena, Nelida Maria. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
XI Congreso Argentino de Bioinformática y Biología Computacional
Buenos Aires
Argentina
Asociacion Argentina de Bioinformática y Biología Computacional
Materia
Cribado Virtual
COVID-19
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/170855
Acceder
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spelling Drug repurposing to find inhibitors of SARS-CoV-2 main proteaseConti, German AndresGómez Chávez, José LeonardoAngelina, Emilio LuisPeruchena, Nelida MariaCribado VirtualCOVID-19https://purl.org/becyt/ford/1.2https://purl.org/becyt/ford/1Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the strain of coronavirus that causes coronavirus disease 2019 (COVID-19), the respiratory illness responsible for the COVID-19 pandemic. As of October 2021, with about 6 billion doses of COVID-19 vaccines administered globally, the world is slowly returning back to normality. However, there is still a need for novel therapeutics for people that contracted the disease either because they were not vaccinated or because the vaccine was not effective for them. Drug repurposing is a strategy for identifying new uses for approved drugs that has the advantage, over conventional approaches that attempt to develop a drug from scratch, that the time frame of the overall process can be significantly reduced because of the few number of clinical trials required. In this work, a structure-based virtual screening of FDA-approved drugs was performed for repositioning as potential inhibitors of the main protease Mpro of SARS-CoV-2. 12 drugs were prioritized from the Virtual Screening campaigns as potential inhibitors of the Mpro enzyme. Some of the selected compounds turned out to be antiviral drugs already being tested in COVID-19 clinical trials or used to alleviate symptoms of the disease. Curiously, the most promising candidate is the naturally occurring broad spectrum antibiotic Oxytetracycline (OTC). This drug has largely outperformed the remaining selected candidates along all filtering steps of the virtual screening workflow. The closely related tetracycline-derived drug Doxycycline (DOX) recently has proven to reduce the viral load in Vero cells infected with SARS-CoV-2. Since OTC but not DOX surpassed the more stringent filters in the late stages of our virtual screening pipeline, we suspect that OTC will show even higher antiviral activity than DOX in viral replication experiments.Considering our computational findings together with the proven antiviral properties of DOX, we believe it is worth testing OTC in prospective viral replication studies. We encourage the scientific community working on COVID-19 projects to include this repurposing candidate on their experimental screening pipelines.Fil: Conti, German Andres. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; ArgentinaFil: Gómez Chávez, José Leonardo. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; ArgentinaFil: Angelina, Emilio Luis. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; ArgentinaFil: Peruchena, Nelida Maria. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; ArgentinaXI Congreso Argentino de Bioinformática y Biología ComputacionalBuenos AiresArgentinaAsociacion Argentina de Bioinformática y Biología ComputacionalAsociación Argentina de Bioinformática y Biología Computacional2021info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/170855Drug repurposing to find inhibitors of SARS-CoV-2 main protease; XI Congreso Argentino de Bioinformática y Biología Computacional; Buenos Aires; Argentina; 2021; 1-2CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://2021.a2b2c.org.ar/Book.pdfInternacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:34:07Zoai:ri.conicet.gov.ar:11336/170855instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:34:07.858CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Drug repurposing to find inhibitors of SARS-CoV-2 main protease
title Drug repurposing to find inhibitors of SARS-CoV-2 main protease
spellingShingle Drug repurposing to find inhibitors of SARS-CoV-2 main protease
Conti, German Andres
Cribado Virtual
COVID-19
title_short Drug repurposing to find inhibitors of SARS-CoV-2 main protease
title_full Drug repurposing to find inhibitors of SARS-CoV-2 main protease
title_fullStr Drug repurposing to find inhibitors of SARS-CoV-2 main protease
title_full_unstemmed Drug repurposing to find inhibitors of SARS-CoV-2 main protease
title_sort Drug repurposing to find inhibitors of SARS-CoV-2 main protease
dc.creator.none.fl_str_mv Conti, German Andres
Gómez Chávez, José Leonardo
Angelina, Emilio Luis
Peruchena, Nelida Maria
author Conti, German Andres
author_facet Conti, German Andres
Gómez Chávez, José Leonardo
Angelina, Emilio Luis
Peruchena, Nelida Maria
author_role author
author2 Gómez Chávez, José Leonardo
Angelina, Emilio Luis
Peruchena, Nelida Maria
author2_role author
author
author
dc.subject.none.fl_str_mv Cribado Virtual
COVID-19
topic Cribado Virtual
COVID-19
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.2
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the strain of coronavirus that causes coronavirus disease 2019 (COVID-19), the respiratory illness responsible for the COVID-19 pandemic. As of October 2021, with about 6 billion doses of COVID-19 vaccines administered globally, the world is slowly returning back to normality. However, there is still a need for novel therapeutics for people that contracted the disease either because they were not vaccinated or because the vaccine was not effective for them. Drug repurposing is a strategy for identifying new uses for approved drugs that has the advantage, over conventional approaches that attempt to develop a drug from scratch, that the time frame of the overall process can be significantly reduced because of the few number of clinical trials required. In this work, a structure-based virtual screening of FDA-approved drugs was performed for repositioning as potential inhibitors of the main protease Mpro of SARS-CoV-2. 12 drugs were prioritized from the Virtual Screening campaigns as potential inhibitors of the Mpro enzyme. Some of the selected compounds turned out to be antiviral drugs already being tested in COVID-19 clinical trials or used to alleviate symptoms of the disease. Curiously, the most promising candidate is the naturally occurring broad spectrum antibiotic Oxytetracycline (OTC). This drug has largely outperformed the remaining selected candidates along all filtering steps of the virtual screening workflow. The closely related tetracycline-derived drug Doxycycline (DOX) recently has proven to reduce the viral load in Vero cells infected with SARS-CoV-2. Since OTC but not DOX surpassed the more stringent filters in the late stages of our virtual screening pipeline, we suspect that OTC will show even higher antiviral activity than DOX in viral replication experiments.Considering our computational findings together with the proven antiviral properties of DOX, we believe it is worth testing OTC in prospective viral replication studies. We encourage the scientific community working on COVID-19 projects to include this repurposing candidate on their experimental screening pipelines.
Fil: Conti, German Andres. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina
Fil: Gómez Chávez, José Leonardo. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Angelina, Emilio Luis. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Peruchena, Nelida Maria. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
XI Congreso Argentino de Bioinformática y Biología Computacional
Buenos Aires
Argentina
Asociacion Argentina de Bioinformática y Biología Computacional
description Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the strain of coronavirus that causes coronavirus disease 2019 (COVID-19), the respiratory illness responsible for the COVID-19 pandemic. As of October 2021, with about 6 billion doses of COVID-19 vaccines administered globally, the world is slowly returning back to normality. However, there is still a need for novel therapeutics for people that contracted the disease either because they were not vaccinated or because the vaccine was not effective for them. Drug repurposing is a strategy for identifying new uses for approved drugs that has the advantage, over conventional approaches that attempt to develop a drug from scratch, that the time frame of the overall process can be significantly reduced because of the few number of clinical trials required. In this work, a structure-based virtual screening of FDA-approved drugs was performed for repositioning as potential inhibitors of the main protease Mpro of SARS-CoV-2. 12 drugs were prioritized from the Virtual Screening campaigns as potential inhibitors of the Mpro enzyme. Some of the selected compounds turned out to be antiviral drugs already being tested in COVID-19 clinical trials or used to alleviate symptoms of the disease. Curiously, the most promising candidate is the naturally occurring broad spectrum antibiotic Oxytetracycline (OTC). This drug has largely outperformed the remaining selected candidates along all filtering steps of the virtual screening workflow. The closely related tetracycline-derived drug Doxycycline (DOX) recently has proven to reduce the viral load in Vero cells infected with SARS-CoV-2. Since OTC but not DOX surpassed the more stringent filters in the late stages of our virtual screening pipeline, we suspect that OTC will show even higher antiviral activity than DOX in viral replication experiments.Considering our computational findings together with the proven antiviral properties of DOX, we believe it is worth testing OTC in prospective viral replication studies. We encourage the scientific community working on COVID-19 projects to include this repurposing candidate on their experimental screening pipelines.
publishDate 2021
dc.date.none.fl_str_mv 2021
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info:eu-repo/semantics/conferenceObject
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http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/170855
Drug repurposing to find inhibitors of SARS-CoV-2 main protease; XI Congreso Argentino de Bioinformática y Biología Computacional; Buenos Aires; Argentina; 2021; 1-2
CONICET Digital
CONICET
url http://hdl.handle.net/11336/170855
identifier_str_mv Drug repurposing to find inhibitors of SARS-CoV-2 main protease; XI Congreso Argentino de Bioinformática y Biología Computacional; Buenos Aires; Argentina; 2021; 1-2
CONICET Digital
CONICET
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dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv Asociación Argentina de Bioinformática y Biología Computacional
publisher.none.fl_str_mv Asociación Argentina de Bioinformática y Biología Computacional
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