Publication:
ACE2-decorated virus-like particles effectively block SARS-CoV-2 infection

dc.contributor.coauthorSupramaniam, Aroon
dc.contributor.coauthorIdris, Adi
dc.contributor.departmentKUTTAM (Koç University Research Center for Translational Medicine)
dc.contributor.departmentGraduate School of Health Sciences
dc.contributor.departmentGraduate School of Sciences and Engineering
dc.contributor.departmentSchool of Medicine
dc.contributor.kuauthorBayraktar, Canan
dc.contributor.kuauthorDurgun, Ayşegül
dc.contributor.kuauthorKayabölen, Alişan
dc.contributor.kuauthorKök, İpek
dc.contributor.kuauthorOdabaş, Arda
dc.contributor.kuauthorÖnder, Tuğba Bağcı
dc.contributor.kuauthorSevinç, Kenan
dc.contributor.schoolcollegeinstituteGRADUATE SCHOOL OF HEALTH SCIENCES
dc.contributor.schoolcollegeinstituteGRADUATE SCHOOL OF SCIENCES AND ENGINEERING
dc.contributor.schoolcollegeinstituteResearch Center
dc.contributor.schoolcollegeinstituteSCHOOL OF MEDICINE
dc.date.accessioned2024-12-29T09:38:03Z
dc.date.issued2024
dc.description.abstractPurpose: Over the past three years, extensive research has been dedicated to understanding and combating COVID-19. Targeting the interaction between the SARS-CoV-2 Spike protein and the ACE2 receptor has emerged as a promising therapeutic strategy against SARS-CoV-2. This study aimed to develop ACE2-coated virus-like particles (ACE2-VLPs), which can be utilized to prevent viral entry into host cells and efficiently neutralize the virus. Methods: Virus-like particles were generated through the utilization of a packaging plasmid in conjunction with a plasmid containing the ACE2 envelope sequence. Subsequently, ACE2-VLPs and ACE2-EVs were purified via ultracentrifugation. The quantification of VLPs was validated through multiple methods, including Nanosight 3000, TEM imaging, and Western blot analysis. Various packaging systems were explored to optimize the ACE2-VLP configuration for enhanced neutralization capabilities. The evaluation of neutralization effectiveness was conducted using pseudoviruses bearing different spike protein variants. Furthermore, the study assessed the neutralization potential against the Omicron BA.1 variant in Vero E6 cells. Results: ACE2-VLPs showed a high neutralization capacity even at low doses and demonstrated superior efficacy in in vitro pseudoviral assays compared to extracellular vesicles carrying ACE2. ACE2-VLPs remained stable under various environmental temperatures and effectively blocked all tested variants of concern in vitro. Notably, they exhibited significant neutralization against Omicron BA.1 variant in Vero E6 cells. Given their superior efficacy compared to extracellular vesicles and proven success against live virus, ACE2-VLPs stand out as crucial candidates for treating SARS-CoV-2 infections. Conclusion: This novel therapeutic approach of coating VLPs with receptor particles provides a proof-of-concept for designing effective neutralization strategies for other viral diseases in the future.
dc.description.indexedbyWOS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.openaccessgold
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuTÜBİTAK
dc.description.sponsorshipWe thank Goektug Karab & imath;y & imath;k for his help with the image analysis. The authors acknowledge the financial support and use of the services and facilities of the Koc University Research Center for Translational Medicine (KUTTAM) . We thank the Molecular Imaging Center and TEM Facility at Koc University N2Star. The CR3022 antibody was obtained from Dr. Naphak Modhiran and Assoc. Prof. Dan Watterson from the School of Chemistry and Molecular Biosciences, The University of Queensland, QLD, Australia. C.B. is supported by a TUBITAK-BIDEB 2211 scholarship for PhD studies. This paper has been uploaded to bioRxiv as a preprint: https:// www.biorxiv.org/content/10.1101/2023.09.19.558424v1 .
dc.description.volume19
dc.identifier.doi10.2147/IJN.S446093
dc.identifier.issn1178-2013
dc.identifier.quartileQ1
dc.identifier.scopus2-s2.0-85199014420
dc.identifier.urihttps://doi.org/10.2147/IJN.S446093
dc.identifier.urihttps://hdl.handle.net/20.500.14288/22569
dc.identifier.wos1266474900001
dc.keywordsACE2
dc.keywordsVirus like particles
dc.keywordsSARS-CoV-2
dc.keywordsNeutralization
dc.keywordsVLP
dc.keywordsEscape mutations
dc.keywordsSpike protein
dc.language.isoeng
dc.publisherDove Medical Press Ltd
dc.relation.ispartofInternational Journal of Nanomedicine
dc.subjectNanoscience and nanotechnology
dc.subjectPharmacology and pharmacy
dc.titleACE2-decorated virus-like particles effectively block SARS-CoV-2 infection
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.kuauthorBayraktar, Canan
local.contributor.kuauthorKayabölen, Alişan
local.contributor.kuauthorOdabaş, Arda
local.contributor.kuauthorDurgun, Ayşegül
local.contributor.kuauthorKök, İpek
local.contributor.kuauthorSevinç, Kenan
local.contributor.kuauthorÖnder, Tuğba Bağcı
local.publication.orgunit1GRADUATE SCHOOL OF HEALTH SCIENCES
local.publication.orgunit1GRADUATE SCHOOL OF SCIENCES AND ENGINEERING
local.publication.orgunit1SCHOOL OF MEDICINE
local.publication.orgunit1Research Center
local.publication.orgunit2KUTTAM (Koç University Research Center for Translational Medicine)
local.publication.orgunit2School of Medicine
local.publication.orgunit2Graduate School of Health Sciences
local.publication.orgunit2Graduate School of Sciences and Engineering
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