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...
- 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:expeditiorepositorio.utadeo.edu.co:20.500.12010/14580 |
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Expeditio: repositorio UTadeo |
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|
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 |
bitstream.checksum.fl_str_mv |
d5a5153b4a0a1b48e5360e913c35b91d abceeb1c943c50d3343516f9dbfc110f |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 |
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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 |