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ANTIVIRAL DRUGS

Drugging viral factories

Nature Chemical Biology volume 17, page 929 (2021)Cite this article

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Nature 595, 596–599 (2021)

Human respiratory syncytial virus (RSV) causes respiratory infections and induces the formation of inclusion bodies (IBs) or ‘viral factories’, which consist of viral proteins and genomic RNA, where mRNA synthesis, genome replication and packaging take place. IBs of negative-strand RNA viruses are biomolecular condensates, a specific type of subcellular compartment formed through liquid–liquid phase separation. Risso-Ballester et al. identified two small molecules, steroidal alkaloid cyclopamine (CPM) and its ethoxy analog A3E, which target the IB condensates resulting in disorganization and hardening of the IBs and preventing viral replication. The small-molecule effects are dependent on the presence of viral transcription factor M2-1 in the IBs, as recombinant RSV viruses, expressing the M2-1(R151K) mutant, were resistant to the effects of CPM and A3E. Finally, CPM and A3E could block RSV replication in a mouse model, which demonstrates that their condensate-hardening properties translate to antiviral effects in vivo. This study paves the way for the development of antiviral drugs against viruses that use condensate formation as an essential step in their life cycle and other pathophysiological processes that involve biomolecular condensates.

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  1. Nature Chemical Biology https://www.nature.com/nchembio

    Majda Bratovič

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  1. Majda Bratovič
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Correspondence to Majda Bratovič.

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Bratovič, M. Drugging viral factories. Nat Chem Biol 17, 929 (2021). https://doi.org/10.1038/s41589-021-00872-w

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