Computer-aided drug design against spike glycoprotein of SARS-CoV-2 to aid COVID-19 treatment

Background: SARS-CoV-2 has the Spike glycoprotein (S) which is crucial in attachment with host receptor and cell entry leading to COVID-19 infection. The current study was conducted to explore drugs against Receptor Binding Domain (RBD) of SARS-CoV-2 using in silico pharmacophore modelling and virtu...

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Autores:
Tipo de recurso:
Article of investigation
Fecha de publicación:
2020
Institución:
Universidad de Bogotá Jorge Tadeo Lozano
Repositorio:
Expeditio: repositorio UTadeo
Idioma:
eng
OAI Identifier:
oai:expeditiorepositorio.utadeo.edu.co:20.500.12010/14580
Acceso en línea:
https://doi.org/10.1016/j.heliyon.2020.e05278
http://hdl.handle.net/20.500.12010/14580
Palabra clave:
Bioinformatics
Immunology
Computer-aided drug design
Drug binding
Infectious disease
Viral protein
Viruses
SARS-CoV-2
Receptor binding domain
Virtual screening
Lead compounds
Anti-Viral drugs
COVID-19
Síndrome respiratorio agudo grave
COVID-19
SARS-CoV-2
Coronavirus
Rights
License
Abierto (Texto Completo)
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oai_identifier_str oai:expeditiorepositorio.utadeo.edu.co:20.500.12010/14580
network_acronym_str UTADEO2
network_name_str Expeditio: repositorio UTadeo
repository_id_str
dc.title.spa.fl_str_mv Computer-aided drug design against spike glycoprotein of SARS-CoV-2 to aid COVID-19 treatment
title Computer-aided drug design against spike glycoprotein of SARS-CoV-2 to aid COVID-19 treatment
spellingShingle Computer-aided drug design against spike glycoprotein of SARS-CoV-2 to aid COVID-19 treatment
Bioinformatics
Immunology
Computer-aided drug design
Drug binding
Infectious disease
Viral protein
Viruses
SARS-CoV-2
Receptor binding domain
Virtual screening
Lead compounds
Anti-Viral drugs
COVID-19
Síndrome respiratorio agudo grave
COVID-19
SARS-CoV-2
Coronavirus
title_short Computer-aided drug design against spike glycoprotein of SARS-CoV-2 to aid COVID-19 treatment
title_full Computer-aided drug design against spike glycoprotein of SARS-CoV-2 to aid COVID-19 treatment
title_fullStr Computer-aided drug design against spike glycoprotein of SARS-CoV-2 to aid COVID-19 treatment
title_full_unstemmed Computer-aided drug design against spike glycoprotein of SARS-CoV-2 to aid COVID-19 treatment
title_sort Computer-aided drug design against spike glycoprotein of SARS-CoV-2 to aid COVID-19 treatment
dc.subject.spa.fl_str_mv Bioinformatics
Immunology
Computer-aided drug design
Drug binding
Infectious disease
Viral protein
Viruses
SARS-CoV-2
Receptor binding domain
Virtual screening
Lead compounds
Anti-Viral drugs
COVID-19
topic Bioinformatics
Immunology
Computer-aided drug design
Drug binding
Infectious disease
Viral protein
Viruses
SARS-CoV-2
Receptor binding domain
Virtual screening
Lead compounds
Anti-Viral drugs
COVID-19
Síndrome respiratorio agudo grave
COVID-19
SARS-CoV-2
Coronavirus
dc.subject.lemb.spa.fl_str_mv Síndrome respiratorio agudo grave
COVID-19
SARS-CoV-2
Coronavirus
description Background: SARS-CoV-2 has the Spike glycoprotein (S) which is crucial in attachment with host receptor and cell entry leading to COVID-19 infection. The current study was conducted to explore drugs against Receptor Binding Domain (RBD) of SARS-CoV-2 using in silico pharmacophore modelling and virtual screening approach to combat COVID-19. Methods: All the available sequences of RBD in NCBI were retrieved and multiple aligned to get insight into its diversity. The 3D structure of RBD was modelled and the conserved region was used as a template to design pharmacophore using LigandScout. Lead compounds were screened using Cambridge, Drugbank, ZINC and TIMBLE databases and these identified lead compounds were screened for their toxicity and Lipinski's rule of five. Molecular docking of shortlisted lead compounds was performed using AutoDock Vina and interacting residues were visualized. Results: Active residues of Receptor Binding Motif (RBM) in S, involved in interaction with receptor, were found to be conserved in all 483 sequences. Using this RBM motif as a pharmacophore a total of 1327 lead compounds were predicted initially from all databases, however, only eight molecules fit the criteria for safe oral drugs. Conclusion: The RBM region of S interacts with Angiotensin Converting Enzyme 2 (ACE2) receptor and Glucose Regulated Protein 78 (GRP78) to mediate viral entry. Based on in silico analysis, the lead compounds scrutinized herewith interact with S, hence, can prevent its internalization in cell using ACE2 and GRP78 receptor. The compounds predicted in this study are based on rigorous computational analysis and the evaluation of predicted lead compounds can be promising in experimental studies.
publishDate 2020
dc.date.accessioned.none.fl_str_mv 2020-10-19T16:56:08Z
dc.date.available.none.fl_str_mv 2020-10-19T16:56:08Z
dc.date.created.none.fl_str_mv 2020
dc.type.local.spa.fl_str_mv Artículo
dc.type.coar.spa.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
format http://purl.org/coar/resource_type/c_2df8fbb1
dc.identifier.issn.spa.fl_str_mv 2405-8440
dc.identifier.other.spa.fl_str_mv https://doi.org/10.1016/j.heliyon.2020.e05278
dc.identifier.uri.none.fl_str_mv http://hdl.handle.net/20.500.12010/14580
dc.identifier.doi.spa.fl_str_mv https://doi.org/10.1016/j.heliyon.2020.e05278
identifier_str_mv 2405-8440
url https://doi.org/10.1016/j.heliyon.2020.e05278
http://hdl.handle.net/20.500.12010/14580
dc.language.iso.spa.fl_str_mv eng
language eng
dc.rights.coar.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.rights.local.spa.fl_str_mv Abierto (Texto Completo)
rights_invalid_str_mv Abierto (Texto Completo)
http://purl.org/coar/access_right/c_abf2
dc.format.extent.spa.fl_str_mv 10 páginas
dc.format.mimetype.spa.fl_str_mv application/pdf
dc.publisher.spa.fl_str_mv Heliyon
dc.source.spa.fl_str_mv reponame:Expeditio Repositorio Institucional UJTL
instname:Universidad de Bogotá Jorge Tadeo Lozano
instname_str Universidad de Bogotá Jorge Tadeo Lozano
institution Universidad de Bogotá Jorge Tadeo Lozano
reponame_str Expeditio Repositorio Institucional UJTL
collection Expeditio Repositorio Institucional UJTL
bitstream.url.fl_str_mv https://expeditiorepositorio.utadeo.edu.co/bitstream/20.500.12010/14580/3/Computer-aided-drug-design-against-spike-glycoprotein-of-SARS-CoV-_2020_Heli.pdf.jpg
https://expeditiorepositorio.utadeo.edu.co/bitstream/20.500.12010/14580/2/license.txt
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repository.name.fl_str_mv Repositorio Institucional - Universidad Jorge Tadeo Lozano
repository.mail.fl_str_mv expeditio@utadeo.edu.co
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spelling 2020-10-19T16:56:08Z2020-10-19T16:56:08Z20202405-8440https://doi.org/10.1016/j.heliyon.2020.e05278http://hdl.handle.net/20.500.12010/14580https://doi.org/10.1016/j.heliyon.2020.e05278Background: SARS-CoV-2 has the Spike glycoprotein (S) which is crucial in attachment with host receptor and cell entry leading to COVID-19 infection. The current study was conducted to explore drugs against Receptor Binding Domain (RBD) of SARS-CoV-2 using in silico pharmacophore modelling and virtual screening approach to combat COVID-19. Methods: All the available sequences of RBD in NCBI were retrieved and multiple aligned to get insight into its diversity. The 3D structure of RBD was modelled and the conserved region was used as a template to design pharmacophore using LigandScout. Lead compounds were screened using Cambridge, Drugbank, ZINC and TIMBLE databases and these identified lead compounds were screened for their toxicity and Lipinski's rule of five. Molecular docking of shortlisted lead compounds was performed using AutoDock Vina and interacting residues were visualized. Results: Active residues of Receptor Binding Motif (RBM) in S, involved in interaction with receptor, were found to be conserved in all 483 sequences. Using this RBM motif as a pharmacophore a total of 1327 lead compounds were predicted initially from all databases, however, only eight molecules fit the criteria for safe oral drugs. Conclusion: The RBM region of S interacts with Angiotensin Converting Enzyme 2 (ACE2) receptor and Glucose Regulated Protein 78 (GRP78) to mediate viral entry. Based on in silico analysis, the lead compounds scrutinized herewith interact with S, hence, can prevent its internalization in cell using ACE2 and GRP78 receptor. The compounds predicted in this study are based on rigorous computational analysis and the evaluation of predicted lead compounds can be promising in experimental studies.10 páginasapplication/pdfengHeliyonreponame:Expeditio Repositorio Institucional UJTLinstname:Universidad de Bogotá Jorge Tadeo LozanoBioinformaticsImmunologyComputer-aided drug designDrug bindingInfectious diseaseViral proteinVirusesSARS-CoV-2Receptor binding domainVirtual screeningLead compoundsAnti-Viral drugsCOVID-19Síndrome respiratorio agudo graveCOVID-19SARS-CoV-2CoronavirusComputer-aided drug design against spike glycoprotein of SARS-CoV-2 to aid COVID-19 treatmentArtículohttp://purl.org/coar/resource_type/c_2df8fbb1Abierto (Texto Completo)http://purl.org/coar/access_right/c_abf2Shehroz, MuhammadZaheer, TahreemHussain, TanveerTHUMBNAILComputer-aided-drug-design-against-spike-glycoprotein-of-SARS-CoV-_2020_Heli.pdf.jpgComputer-aided-drug-design-against-spike-glycoprotein-of-SARS-CoV-_2020_Heli.pdf.jpgIM Thumbnailimage/jpeg23038https://expeditiorepositorio.utadeo.edu.co/bitstream/20.500.12010/14580/3/Computer-aided-drug-design-against-spike-glycoprotein-of-SARS-CoV-_2020_Heli.pdf.jpgd5a5153b4a0a1b48e5360e913c35b91dMD53open accessLICENSElicense.txtlicense.txttext/plain; charset=utf-82938https://expeditiorepositorio.utadeo.edu.co/bitstream/20.500.12010/14580/2/license.txtabceeb1c943c50d3343516f9dbfc110fMD52open access20.500.12010/14580oai:expeditiorepositorio.utadeo.edu.co:20.500.12010/145802021-03-12 18:33:34.343metadata only accessRepositorio Institucional - Universidad Jorge Tadeo Lozanoexpeditio@utadeo.edu.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