miR-24-3p Is Antiviral Against SARS-CoV-2 by Downregulating Critical Host Entry Factors
Despite all the progress in treating SARS-CoV-2, escape mutants to current therapies remain a constant concern. Promising alternative treatments for current and future coronaviruses are those that limit escape mutants by inhibiting multiple pathogenic targets, analogous to the current strategies for...
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MDPI AG
2024-11-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/16/12/1844 |
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| author | Parrish Evers Spencer M. Uguccioni Nadine Ahmed Magen E. Francis Alyson A. Kelvin John P. Pezacki |
| author_facet | Parrish Evers Spencer M. Uguccioni Nadine Ahmed Magen E. Francis Alyson A. Kelvin John P. Pezacki |
| author_sort | Parrish Evers |
| collection | DOAJ |
| description | Despite all the progress in treating SARS-CoV-2, escape mutants to current therapies remain a constant concern. Promising alternative treatments for current and future coronaviruses are those that limit escape mutants by inhibiting multiple pathogenic targets, analogous to the current strategies for treating HCV and HIV. With increasing popularity and ease of manufacturing of RNA technologies for vaccines and drugs, therapeutic microRNAs represent a promising option. In the present work, miR-24-3p was identified to inhibit SARS-CoV-2 entry, replication, and production; furthermore, this inhibition was retained against common mutations improving SARS-CoV-2 fitness. To determine the mechanism of action, bioinformatic tools were employed, identifying numerous potential effectors promoting infection targeted by miR-24-3p. Of these targets, several key host proteins for priming and facilitating SARS-CoV-2 entry were identified: furin, NRP1, NRP2, and SREBP2. With further experimental analysis, we show that miR-24-3p directly downregulates these viral entry factors to impede infection when producing virions and when infecting the target cell. Furthermore, we compare the findings with coronavirus, HCoV-229E, which relies on different factors strengthening the miR-24-3p mechanism. Taken together, the following work suggests that miR-24-3p could be an avenue to treat current coronaviruses and those likely to emerge. |
| format | Article |
| id | doaj-art-61de43d7afec4edcb5c6840f8c72ea98 |
| institution | Kabale University |
| issn | 1999-4915 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj-art-61de43d7afec4edcb5c6840f8c72ea982024-12-27T14:59:01ZengMDPI AGViruses1999-49152024-11-011612184410.3390/v16121844miR-24-3p Is Antiviral Against SARS-CoV-2 by Downregulating Critical Host Entry FactorsParrish Evers0Spencer M. Uguccioni1Nadine Ahmed2Magen E. Francis3Alyson A. Kelvin4John P. Pezacki5Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, ON K1N 6N6, CanadaDepartment of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, ON K1N 6N6, CanadaDepartment of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, ON K1N 6N6, CanadaVaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK S7N 5E3, CanadaVaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK S7N 5E3, CanadaDepartment of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, ON K1N 6N6, CanadaDespite all the progress in treating SARS-CoV-2, escape mutants to current therapies remain a constant concern. Promising alternative treatments for current and future coronaviruses are those that limit escape mutants by inhibiting multiple pathogenic targets, analogous to the current strategies for treating HCV and HIV. With increasing popularity and ease of manufacturing of RNA technologies for vaccines and drugs, therapeutic microRNAs represent a promising option. In the present work, miR-24-3p was identified to inhibit SARS-CoV-2 entry, replication, and production; furthermore, this inhibition was retained against common mutations improving SARS-CoV-2 fitness. To determine the mechanism of action, bioinformatic tools were employed, identifying numerous potential effectors promoting infection targeted by miR-24-3p. Of these targets, several key host proteins for priming and facilitating SARS-CoV-2 entry were identified: furin, NRP1, NRP2, and SREBP2. With further experimental analysis, we show that miR-24-3p directly downregulates these viral entry factors to impede infection when producing virions and when infecting the target cell. Furthermore, we compare the findings with coronavirus, HCoV-229E, which relies on different factors strengthening the miR-24-3p mechanism. Taken together, the following work suggests that miR-24-3p could be an avenue to treat current coronaviruses and those likely to emerge.https://www.mdpi.com/1999-4915/16/12/1844SARS-CoV-2COVID-19microRNAmiR-24miR-24-3pHCoV-229E |
| spellingShingle | Parrish Evers Spencer M. Uguccioni Nadine Ahmed Magen E. Francis Alyson A. Kelvin John P. Pezacki miR-24-3p Is Antiviral Against SARS-CoV-2 by Downregulating Critical Host Entry Factors Viruses SARS-CoV-2 COVID-19 microRNA miR-24 miR-24-3p HCoV-229E |
| title | miR-24-3p Is Antiviral Against SARS-CoV-2 by Downregulating Critical Host Entry Factors |
| title_full | miR-24-3p Is Antiviral Against SARS-CoV-2 by Downregulating Critical Host Entry Factors |
| title_fullStr | miR-24-3p Is Antiviral Against SARS-CoV-2 by Downregulating Critical Host Entry Factors |
| title_full_unstemmed | miR-24-3p Is Antiviral Against SARS-CoV-2 by Downregulating Critical Host Entry Factors |
| title_short | miR-24-3p Is Antiviral Against SARS-CoV-2 by Downregulating Critical Host Entry Factors |
| title_sort | mir 24 3p is antiviral against sars cov 2 by downregulating critical host entry factors |
| topic | SARS-CoV-2 COVID-19 microRNA miR-24 miR-24-3p HCoV-229E |
| url | https://www.mdpi.com/1999-4915/16/12/1844 |
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