Targeting SARS-CoV-2 Variants with Nucleic Acid Therapeutic Nanoparticle Conjugates
The emergence of SARS-CoV-2 variants is cause for concern, because these may become resistant to current vaccines and antiviral drugs in development. Current drugs target viral proteins, resulting in a critical need for RNA-targeted nanomedicines. To address this, a comparative analysis of SARS-CoV-...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-10-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/14/10/1012 |
| _version_ | 1797513490236178432 |
|---|---|
| author | Hanah F. Huber Majid Jaberi-Douraki Sarah DeVader Cesar Aparicio-Lopez Juliet Nava-Chavez Xuan Xu Nuwan Indika Millagaha Gedara Natasha N. Gaudreault Robert K. Delong |
| author_facet | Hanah F. Huber Majid Jaberi-Douraki Sarah DeVader Cesar Aparicio-Lopez Juliet Nava-Chavez Xuan Xu Nuwan Indika Millagaha Gedara Natasha N. Gaudreault Robert K. Delong |
| author_sort | Hanah F. Huber |
| collection | DOAJ |
| description | The emergence of SARS-CoV-2 variants is cause for concern, because these may become resistant to current vaccines and antiviral drugs in development. Current drugs target viral proteins, resulting in a critical need for RNA-targeted nanomedicines. To address this, a comparative analysis of SARS-CoV-2 variants was performed. Several highly conserved sites were identified, of which the most noteworthy is a partial homopurine palindrome site with >99% conservation within the coding region. This sequence was compared among recently emerged, highly infectious SARS-CoV-2 variants. Conservation of the site was maintained among these emerging variants, further contributing to its potential as a regulatory target site for SARS-CoV-2. RNAfold was used to predict the structures of the highly conserved sites, with some resulting structures being common among coronaviridae. An RNA-level regulatory map of the conserved regions of SARS-CoV-2 was produced based on the predicted structures, with each representing potential target sites for antisense oligonucleotides, triplex-forming oligomers, and aptamers. Additionally, homopurine/homopyrimidine sequences within the viral genome were identified. These sequences also demonstrate appropriate target sites for antisense oligonucleotides and triplex-forming oligonucleotides. An experimental strategy to investigate these is summarized along with potential nanoparticle types for delivery, and the advantages and disadvantages of each are discussed. |
| first_indexed | 2024-03-10T06:17:19Z |
| format | Article |
| id | doaj.art-83313e956ff0473c9b069ebae336eb1e |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T06:17:19Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-83313e956ff0473c9b069ebae336eb1e2023-11-22T19:36:04ZengMDPI AGPharmaceuticals1424-82472021-10-011410101210.3390/ph14101012Targeting SARS-CoV-2 Variants with Nucleic Acid Therapeutic Nanoparticle ConjugatesHanah F. Huber0Majid Jaberi-Douraki1Sarah DeVader2Cesar Aparicio-Lopez3Juliet Nava-Chavez4Xuan Xu5Nuwan Indika Millagaha Gedara6Natasha N. Gaudreault7Robert K. Delong8Nanotechnology Innovation Center, Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA1DATA Consortium and Department of Mathematics, Kansas State University Olathe, Olathe, KS 66061, USANanotechnology Innovation Center, Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USANanotechnology Innovation Center, Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USANanotechnology Innovation Center, Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA1DATA Consortium and Department of Mathematics, Kansas State University Olathe, Olathe, KS 66061, USA1DATA Consortium and Department of Mathematics, Kansas State University Olathe, Olathe, KS 66061, USADepartment of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USANanotechnology Innovation Center, Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USAThe emergence of SARS-CoV-2 variants is cause for concern, because these may become resistant to current vaccines and antiviral drugs in development. Current drugs target viral proteins, resulting in a critical need for RNA-targeted nanomedicines. To address this, a comparative analysis of SARS-CoV-2 variants was performed. Several highly conserved sites were identified, of which the most noteworthy is a partial homopurine palindrome site with >99% conservation within the coding region. This sequence was compared among recently emerged, highly infectious SARS-CoV-2 variants. Conservation of the site was maintained among these emerging variants, further contributing to its potential as a regulatory target site for SARS-CoV-2. RNAfold was used to predict the structures of the highly conserved sites, with some resulting structures being common among coronaviridae. An RNA-level regulatory map of the conserved regions of SARS-CoV-2 was produced based on the predicted structures, with each representing potential target sites for antisense oligonucleotides, triplex-forming oligomers, and aptamers. Additionally, homopurine/homopyrimidine sequences within the viral genome were identified. These sequences also demonstrate appropriate target sites for antisense oligonucleotides and triplex-forming oligonucleotides. An experimental strategy to investigate these is summarized along with potential nanoparticle types for delivery, and the advantages and disadvantages of each are discussed.https://www.mdpi.com/1424-8247/14/10/1012SARS-CoV-2nanoparticleTFOvarianthomopurinepalindrome |
| spellingShingle | Hanah F. Huber Majid Jaberi-Douraki Sarah DeVader Cesar Aparicio-Lopez Juliet Nava-Chavez Xuan Xu Nuwan Indika Millagaha Gedara Natasha N. Gaudreault Robert K. Delong Targeting SARS-CoV-2 Variants with Nucleic Acid Therapeutic Nanoparticle Conjugates Pharmaceuticals SARS-CoV-2 nanoparticle TFO variant homopurine palindrome |
| title | Targeting SARS-CoV-2 Variants with Nucleic Acid Therapeutic Nanoparticle Conjugates |
| title_full | Targeting SARS-CoV-2 Variants with Nucleic Acid Therapeutic Nanoparticle Conjugates |
| title_fullStr | Targeting SARS-CoV-2 Variants with Nucleic Acid Therapeutic Nanoparticle Conjugates |
| title_full_unstemmed | Targeting SARS-CoV-2 Variants with Nucleic Acid Therapeutic Nanoparticle Conjugates |
| title_short | Targeting SARS-CoV-2 Variants with Nucleic Acid Therapeutic Nanoparticle Conjugates |
| title_sort | targeting sars cov 2 variants with nucleic acid therapeutic nanoparticle conjugates |
| topic | SARS-CoV-2 nanoparticle TFO variant homopurine palindrome |
| url | https://www.mdpi.com/1424-8247/14/10/1012 |
| work_keys_str_mv | AT hanahfhuber targetingsarscov2variantswithnucleicacidtherapeuticnanoparticleconjugates AT majidjaberidouraki targetingsarscov2variantswithnucleicacidtherapeuticnanoparticleconjugates AT sarahdevader targetingsarscov2variantswithnucleicacidtherapeuticnanoparticleconjugates AT cesarapariciolopez targetingsarscov2variantswithnucleicacidtherapeuticnanoparticleconjugates AT julietnavachavez targetingsarscov2variantswithnucleicacidtherapeuticnanoparticleconjugates AT xuanxu targetingsarscov2variantswithnucleicacidtherapeuticnanoparticleconjugates AT nuwanindikamillagahagedara targetingsarscov2variantswithnucleicacidtherapeuticnanoparticleconjugates AT natashangaudreault targetingsarscov2variantswithnucleicacidtherapeuticnanoparticleconjugates AT robertkdelong targetingsarscov2variantswithnucleicacidtherapeuticnanoparticleconjugates |