Development of CRISPR as an Antiviral Strategy to Combat SARS-CoV-2 and Influenza
Development of CRISPR as an Antiviral Strategy to Combat SARS-CoV-2 and Influenza
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DOI：
10.1016/j.cell.2020.04.020
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发表时间：
2020-05-14
期刊：
影响因子：
64.5
通讯作者：
Qi, Lei S.
中科院分区：
文献类型：
--
作者：
Abbott, Timothy R.;Dhamdhere, Girija;Qi, Lei S.
由SARS-CoV-2病毒引起的2019年冠状病毒病（COVID-19）大流行突出了对抗病毒方法的需求，这些方法可以针对没有有效疫苗或药物的新兴病毒。在这里，我们展示了一种基于CRISPR-Cas 13的策略，PAC-MAN（人类细胞中的预防性抗病毒CRISPR），用于病毒抑制，可以有效地降解人肺上皮细胞中SARS-CoV-2序列和活甲型流感病毒（IAV）的RNA。我们设计并筛选了靶向保守病毒区域的CRISPR RNA（crRNA），并鉴定了靶向SARS-CoV-2的功能性crRNA。这种方法有效地降低了呼吸道上皮细胞中的H1N1 IAV载量。我们的生物信息学分析表明，一组仅6个crRNA就可以靶向90%以上的冠状病毒。随着安全有效的呼吸道给药系统的发展，PAC-MAN有可能成为一种重要的泛冠状病毒抑制策略。
The coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, has highlighted the need for antiviral approaches that can target emerging viruses with no effective vaccines or pharmaceuticals. Here, we demonstrate a CRISPR-Cas13-based strategy, PAC -MAN (prophylactic antiviral CRISPR in human cells), for viral inhibition that can effectively degrade RNA from SARS-CoV-2 sequences and live influenza A virus (IAV) in human lung epithelial cells. We designed and screened CRISPR RNAs (crRNAs) targeting conserved viral regions and identified functional crRNAs targeting SARS-CoV-2. This approach effectively reduced H1 N1 IAV load in respiratory epithelial cells. Our bioinformatic analysis showed that a group of only six crRNAs can target more than 90% of all coronaviruses. With the development of a safe and effective system for respiratory tract delivery, PAC -MAN has the potential to become an important pan-coronavirus inhibition strategy.