Development of CRISPR as a prophylactic strategy to combat novel coronavirus and influenza

Abbott, T. R.; Dhamdhere, G.; Liu, Y.; Lin, X.; Goudy, L. E.; Zeng, L.; Chemparathy, A.; Chmura, S.; Heaton, N.; Debs, R.; Pande, T.; Endy, D.; La Russa, M.; Lewis, D. B.; Qi, L. S.

doi:10.1101/2020.03.13.991307

bioRxiv · 10.1101/2020.03.13.991307

Development of CRISPR as a prophylactic strategy to combat novel coronavirus and influenza

Abbott, T. R.·Dhamdhere, G.·Liu, Y.·Lin, X.·Goudy, L. E.·Zeng, L.·Chemparathy, A.·Chmura, S.·Heaton, N.·Debs, R.·Pande, T.·Endy, D.·La Russa, M.·Lewis, D. B.·Qi, L. S.

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Abstract

The outbreak of the coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), has infected more than 100,000 people worldwide with over 3,000 deaths since December 2019. There is no cure for COVID-19 and the vaccine development is estimated to require 12-18 months. Here we demonstrate a CRISPR-Cas13-based strategy, PAC-MAN (Prophylactic Antiviral CRISPR in huMAN cells), for viral inhibition that can effectively degrade SARS-CoV-2 sequences and live influenza A virus (IAV) genome in human lung epithelial cells. We designed and screened a group of CRISPR RNAs (crRNAs) targeting conserved viral regions and identified functional crRNAs for cleaving SARS-CoV-2. The approach is effective in reducing respiratory cell viral replication for H1N1 IAV. Our bioinformatic analysis showed a group of only six crRNAs can target more than 90% of all coronaviruses. The PAC-MAN approach is potentially a rapidly implementable pan-coronavirus strategy to deal with emerging pandemic strains.

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Abbott, T. R., Dhamdhere, G., Liu, Y., Lin, X., Goudy, L. E., Zeng, L., Chemparathy, A., Chmura, S., Heaton, N., Debs, R., Pande, T., Endy, D., La Russa, M., Lewis, D. B., Qi, L. S.. 2020-03-14. Development of CRISPR as a prophylactic strategy to combat novel coronavirus and influenza. https://doi.org/10.1101/2020.03.13.991307

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