tetano
Editor, Senior Moderator
Nat Commun
. 2022 May 19;13(1):2766.
doi: 10.1038/s41467-022-30546-7.
Broad-spectrum CRISPR-mediated inhibition of SARS-CoV-2 variants and endemic coronaviruses in vitro
Leiping Zeng[SUP] #[/SUP][SUP] 1 [/SUP], Yanxia Liu[SUP] #[/SUP][SUP] 1 [/SUP], Xammy Huu Nguyenla[SUP] 2 [/SUP], Timothy R Abbott[SUP] 1 [/SUP], Mengting Han[SUP] 1 [/SUP], Yanyu Zhu[SUP] 1 [/SUP], Augustine Chemparathy[SUP] 1 [/SUP], Xueqiu Lin[SUP] 1 [/SUP], Xinyi Chen[SUP] 1 [/SUP], Haifeng Wang[SUP] 1 [/SUP], Draven A Rane[SUP] 1 [/SUP], Jordan M Spatz[SUP] 3 [/SUP], Saket Jain[SUP] 4 [/SUP], Arjun Rustagi[SUP] 5 [/SUP], Benjamin Pinsky[SUP] 5 6 [/SUP], Adrianna E Zepeda[SUP] 7 [/SUP], Anastasia P Kadina[SUP] 7 [/SUP], John A Walker 3rd[SUP] 7 [/SUP], Kevin Holden[SUP] 7 [/SUP], Nigel Temperton[SUP] 8 [/SUP], Jennifer R Cochran[SUP] 1 [/SUP], Annelise E Barron[SUP] 1 [/SUP], Michael D Connolly[SUP] 9 [/SUP], Catherine A Blish[SUP] 5 10 [/SUP], David B Lewis[SUP] 3 [/SUP], Sarah A Stanley[SUP] 11 [/SUP], Marie F La Russa[SUP] 12 [/SUP], Lei S Qi[SUP] 13 14 15 [/SUP]
Affiliations
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.
. 2022 May 19;13(1):2766.
doi: 10.1038/s41467-022-30546-7.
Broad-spectrum CRISPR-mediated inhibition of SARS-CoV-2 variants and endemic coronaviruses in vitro
Leiping Zeng[SUP] #[/SUP][SUP] 1 [/SUP], Yanxia Liu[SUP] #[/SUP][SUP] 1 [/SUP], Xammy Huu Nguyenla[SUP] 2 [/SUP], Timothy R Abbott[SUP] 1 [/SUP], Mengting Han[SUP] 1 [/SUP], Yanyu Zhu[SUP] 1 [/SUP], Augustine Chemparathy[SUP] 1 [/SUP], Xueqiu Lin[SUP] 1 [/SUP], Xinyi Chen[SUP] 1 [/SUP], Haifeng Wang[SUP] 1 [/SUP], Draven A Rane[SUP] 1 [/SUP], Jordan M Spatz[SUP] 3 [/SUP], Saket Jain[SUP] 4 [/SUP], Arjun Rustagi[SUP] 5 [/SUP], Benjamin Pinsky[SUP] 5 6 [/SUP], Adrianna E Zepeda[SUP] 7 [/SUP], Anastasia P Kadina[SUP] 7 [/SUP], John A Walker 3rd[SUP] 7 [/SUP], Kevin Holden[SUP] 7 [/SUP], Nigel Temperton[SUP] 8 [/SUP], Jennifer R Cochran[SUP] 1 [/SUP], Annelise E Barron[SUP] 1 [/SUP], Michael D Connolly[SUP] 9 [/SUP], Catherine A Blish[SUP] 5 10 [/SUP], David B Lewis[SUP] 3 [/SUP], Sarah A Stanley[SUP] 11 [/SUP], Marie F La Russa[SUP] 12 [/SUP], Lei S Qi[SUP] 13 14 15 [/SUP]
Affiliations
- PMID: 35589813
- DOI: 10.1038/s41467-022-30546-7
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.