Viruses deploy genetically encoded strategies to coopt host machinery and support viral replicative cycles. Here, we use protein structure similarity to scan for molecular mimicry, manifested by structural similarity between viral and endogenous host proteins, across thousands of cataloged viruses and hosts spanning broad ecological niches and taxonomic range, including bacteria, plants and fungi, invertebrates, and vertebrates. This survey identified over 6,000,000 instances of structural mimicry; more than 70% of viral mimics cannot be discerned through protein sequence alone. We demonstrate that the manner and degree to which viruses exploit molecular mimicry varies by genome size and nucleic acid type and identify 158 human proteins that are mimicked by coronaviruses, providing clues about cellular processes driving pathogenesis. Our observations point to molecular mimicry as a pervasive strategy employed by viruses and indicate that the protein structure space used by a given virus is dictated by the host proteome.

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病毒采用遗传编码策略来整合宿主机制并支持病毒复制周期。在这里，我们使用蛋白质结构相似性来扫描分子拟态，表现为病毒和内源宿主蛋白之间的结构相似性，跨越成千上万种分类病毒和宿主，这些宿主跨越广泛的生态位和分类学范围，包括细菌，植物和真菌，无脊椎动物和脊椎动物。这项调查确定了超过6,000,000个结构模仿实例​​；仅通过蛋白质序列无法识别出超过70％的病毒模拟物。我们证明病毒利用分子模拟的方式和程度随基因组大小和核酸类型的不同而变化，并鉴定出158种被冠状病毒模仿的人类蛋白质，从而提供了驱动发病机理的细胞过程的线索。

补充信息中包含了本文透明的同行评审过程的记录。