Broad-spectrum CRISPR-mediated inhibition of SARS-CoV-2 variants and endemic coronaviruses in vitro
Abstract A major challenge in coronavirus vaccination and treatment is to counteract rapid viral evolution and mutations. Here we demonstrate that CRISPR-Cas13d offers a broad-spectrum antiviral (BSA) to inhibit many SARS-CoV-2 variants and diverse human coronavirus strains with >99% reduction of...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-022-30546-7 |
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| author | Leiping Zeng Yanxia Liu Xammy Huu Wrynla Timothy R. Abbott Mengting Han Yanyu Zhu Augustine Chemparathy Xueqiu Lin Xinyi Chen Haifeng Wang Draven A. Rane Jordan M. Spatz Saket Jain Arjun Rustagi Benjamin Pinsky Adrianna E. Zepeda Anastasia P. Kadina John A. Walker Kevin Holden Nigel Temperton Jennifer R. Cochran Annelise E. Barron Michael D. Connolly Catherine A. Blish David B. Lewis Sarah A. Stanley Marie F. La Russa Lei S. Qi |
| author_facet | Leiping Zeng Yanxia Liu Xammy Huu Wrynla Timothy R. Abbott Mengting Han Yanyu Zhu Augustine Chemparathy Xueqiu Lin Xinyi Chen Haifeng Wang Draven A. Rane Jordan M. Spatz Saket Jain Arjun Rustagi Benjamin Pinsky Adrianna E. Zepeda Anastasia P. Kadina John A. Walker Kevin Holden Nigel Temperton Jennifer R. Cochran Annelise E. Barron Michael D. Connolly Catherine A. Blish David B. Lewis Sarah A. Stanley Marie F. La Russa Lei S. Qi |
| author_sort | Leiping Zeng |
| collection | DOAJ |
| description | Abstract A major challenge in coronavirus vaccination and treatment is to counteract rapid viral evolution and mutations. Here we demonstrate that CRISPR-Cas13d offers a broad-spectrum antiviral (BSA) to inhibit many SARS-CoV-2 variants and diverse human coronavirus strains with >99% reduction of the viral titer. We show that Cas13d-mediated coronavirus inhibition is dependent on the crRNA cellular spatial colocalization with Cas13d and target viral RNA. Cas13d can significantly enhance the therapeutic effects of diverse small molecule drugs against coronaviruses for prophylaxis or treatment purposes, and the best combination reduced viral titer by over four orders of magnitude. Using lipid nanoparticle-mediated RNA delivery, we demonstrate that the Cas13d system can effectively treat infection from multiple variants of coronavirus, including Omicron SARS-CoV-2, in human primary airway epithelium air-liquid interface (ALI) cultures. Our study establishes CRISPR-Cas13 as a BSA which is highly complementary to existing vaccination and antiviral treatment strategies. |
| format | Article |
| id | doaj-art-b19524c1f85b4105af7741efdca8ff41 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2022-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-b19524c1f85b4105af7741efdca8ff412025-08-20T03:45:32ZengNature PortfolioNature Communications2041-17232022-05-0113111610.1038/s41467-022-30546-7Broad-spectrum CRISPR-mediated inhibition of SARS-CoV-2 variants and endemic coronaviruses in vitroLeiping Zeng0Yanxia Liu1Xammy Huu Wrynla2Timothy R. Abbott3Mengting Han4Yanyu Zhu5Augustine Chemparathy6Xueqiu Lin7Xinyi Chen8Haifeng Wang9Draven A. Rane10Jordan M. Spatz11Saket Jain12Arjun Rustagi13Benjamin Pinsky14Adrianna E. Zepeda15Anastasia P. Kadina16John A. Walker17Kevin Holden18Nigel Temperton19Jennifer R. Cochran20Annelise E. Barron21Michael D. Connolly22Catherine A. Blish23David B. Lewis24Sarah A. Stanley25Marie F. La Russa26Lei S. Qi27Department of Bioengineering, Stanford UniversityDepartment of Bioengineering, Stanford UniversityDepartment of Molecular and Cellular Biology, University of CaliforniaDepartment of Bioengineering, Stanford UniversityDepartment of Bioengineering, Stanford UniversityDepartment of Bioengineering, Stanford UniversityDepartment of Bioengineering, Stanford UniversityDepartment of Bioengineering, Stanford UniversityDepartment of Bioengineering, Stanford UniversityDepartment of Bioengineering, Stanford UniversityDepartment of Bioengineering, Stanford UniversityDepartment of Pediatrics, Stanford UniversityUniversity of California San FranciscoDepartment of Medicine, Stanford UniversityDepartment of Medicine, Stanford UniversitySynthego CorporationSynthego CorporationSynthego CorporationSynthego CorporationViral Pseudotype Unit, Medway School of PharmacyDepartment of Bioengineering, Stanford UniversityDepartment of Bioengineering, Stanford UniversityLawrence Berkeley National LaboratoryDepartment of Medicine, Stanford UniversityDepartment of Pediatrics, Stanford UniversityDepartment of Molecular and Cellular Biology, University of CaliforniaDepartment of Bioengineering, Stanford UniversityDepartment of Bioengineering, Stanford UniversityAbstract A major challenge in coronavirus vaccination and treatment is to counteract rapid viral evolution and mutations. Here we demonstrate that CRISPR-Cas13d offers a broad-spectrum antiviral (BSA) to inhibit many SARS-CoV-2 variants and diverse human coronavirus strains with >99% reduction of the viral titer. We show that Cas13d-mediated coronavirus inhibition is dependent on the crRNA cellular spatial colocalization with Cas13d and target viral RNA. Cas13d can significantly enhance the therapeutic effects of diverse small molecule drugs against coronaviruses for prophylaxis or treatment purposes, and the best combination reduced viral titer by over four orders of magnitude. Using lipid nanoparticle-mediated RNA delivery, we demonstrate that the Cas13d system can effectively treat infection from multiple variants of coronavirus, including Omicron SARS-CoV-2, in human primary airway epithelium air-liquid interface (ALI) cultures. Our study establishes CRISPR-Cas13 as a BSA which is highly complementary to existing vaccination and antiviral treatment strategies.https://doi.org/10.1038/s41467-022-30546-7 |
| spellingShingle | Leiping Zeng Yanxia Liu Xammy Huu Wrynla Timothy R. Abbott Mengting Han Yanyu Zhu Augustine Chemparathy Xueqiu Lin Xinyi Chen Haifeng Wang Draven A. Rane Jordan M. Spatz Saket Jain Arjun Rustagi Benjamin Pinsky Adrianna E. Zepeda Anastasia P. Kadina John A. Walker Kevin Holden Nigel Temperton Jennifer R. Cochran Annelise E. Barron Michael D. Connolly Catherine A. Blish David B. Lewis Sarah A. Stanley Marie F. La Russa Lei S. Qi Broad-spectrum CRISPR-mediated inhibition of SARS-CoV-2 variants and endemic coronaviruses in vitro Nature Communications |
| title | Broad-spectrum CRISPR-mediated inhibition of SARS-CoV-2 variants and endemic coronaviruses in vitro |
| title_full | Broad-spectrum CRISPR-mediated inhibition of SARS-CoV-2 variants and endemic coronaviruses in vitro |
| title_fullStr | Broad-spectrum CRISPR-mediated inhibition of SARS-CoV-2 variants and endemic coronaviruses in vitro |
| title_full_unstemmed | Broad-spectrum CRISPR-mediated inhibition of SARS-CoV-2 variants and endemic coronaviruses in vitro |
| title_short | Broad-spectrum CRISPR-mediated inhibition of SARS-CoV-2 variants and endemic coronaviruses in vitro |
| title_sort | broad spectrum crispr mediated inhibition of sars cov 2 variants and endemic coronaviruses in vitro |
| url | https://doi.org/10.1038/s41467-022-30546-7 |
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