Viruses thrive by exploiting the cells they infect but must also produce viral proteins to replicate and infect other cells. As a consequence, they are also susceptible to exploitation by defective versions of themselves that do not produce such proteins. A defective viral genome with deletions in protein-coding genes could still replicate in cells coinfected with full-length viruses, and even replicate faster due to its shorter size, interfering with the replication of the virus. We have created a synthetic defective interfering version of SARS-CoV-2, the virus causing the recent Covid-19 pandemic, assembling parts of the viral genome that do not code for any functional protein but enable it to be replicated and packaged. This synthetic defective genome replicates three times faster than SARS-CoV-2 in coinfected cells, and interferes with it, reducing the viral load of a cell by half in 24 hours. The synthetic genome is transmitted as efficiently as the full-length genome, confirming the location of the putative packaging signal of SARS-CoV-2. A version of such a synthetic construct could be used as a self-promoting antiviral therapy: by enabling replication of the synthetic genome, the virus promotes its own demise.

中文翻译：

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合成缺陷性干扰SARS-CoV-2

病毒通过利用其感染的细胞而蓬勃发展，但还必须产生病毒蛋白才能复制和感染其他细胞。结果，它们也容易被不产生这种蛋白质的自身缺陷形式利用。在蛋白质编码基因中缺失的有缺陷的病毒基因组仍然可以在感染了全长病毒的细胞中复制，甚至由于其较短的大小而复制得更快，从而干扰了病毒的复制。我们创建了SARS-CoV-2的合成有缺陷的干扰版本，该病毒引起最近的Covid-19大流行，组装了病毒基因组的某些部分，这些部分不编码任何功能蛋白，但能够被复制和包装。这种合成缺陷基因组在共同感染的细胞中复制速度比SARS-CoV-2快三倍，并对其产生干扰，在24小时内将细胞的病毒载量降低一半。合成基因组的传输效率与全长基因组一样高，从而确认了SARS-CoV-2假定包装信号的位置。这种合成构建体的一种形式可以用作自我促进的抗病毒治疗：通过使合成基因组复制，病毒可以促进自身的灭亡。