Structural basis of measles virus polymerase inhibition by nonnucleoside inhibitor ERDRP-0519

Dong Wang; Fan Bu; Ge Yang; Bin Liu

doi:10.1038/s41467-025-64128-0

Structural basis of measles virus polymerase inhibition by nonnucleoside inhibitor ERDRP-0519

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Abstract

ERDRP-0519 is a potent nonnucleoside inhibitor active against measles virus (MeV) and other Morbilliviruses. Here we report cryo-EM structures of the compound bound to MeV polymerase complexes at 2.73 Å and 2.48 Å resolution, revealing a unique binding pocket in the RdRp palm subdomain that overlaps the catalytic GDN motif. These findings clarify the basis of resistance mutations, including W671, and provide a foundation for designing next-generation Paramyxovirus antivirals.

Original language	Undefined/Unknown
Article number	9061
Journal	Nature communications
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41467-025-64128-0
State	Published - Dec 2025

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© The Author(s) 2025.

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abstract = "ERDRP-0519 is a potent nonnucleoside inhibitor active against measles virus (MeV) and other Morbilliviruses. Here we report cryo-EM structures of the compound bound to MeV polymerase complexes at 2.73 {\AA} and 2.48 {\AA} resolution, revealing a unique binding pocket in the RdRp palm subdomain that overlaps the catalytic GDN motif. These findings clarify the basis of resistance mutations, including W671, and provide a foundation for designing next-generation Paramyxovirus antivirals.",

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AU - Bu, Fan

AU - Yang, Ge

AU - Liu, Bin

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N2 - ERDRP-0519 is a potent nonnucleoside inhibitor active against measles virus (MeV) and other Morbilliviruses. Here we report cryo-EM structures of the compound bound to MeV polymerase complexes at 2.73 Å and 2.48 Å resolution, revealing a unique binding pocket in the RdRp palm subdomain that overlaps the catalytic GDN motif. These findings clarify the basis of resistance mutations, including W671, and provide a foundation for designing next-generation Paramyxovirus antivirals.

AB - ERDRP-0519 is a potent nonnucleoside inhibitor active against measles virus (MeV) and other Morbilliviruses. Here we report cryo-EM structures of the compound bound to MeV polymerase complexes at 2.73 Å and 2.48 Å resolution, revealing a unique binding pocket in the RdRp palm subdomain that overlaps the catalytic GDN motif. These findings clarify the basis of resistance mutations, including W671, and provide a foundation for designing next-generation Paramyxovirus antivirals.

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DO - 10.1038/s41467-025-64128-0

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Structural basis of measles virus polymerase inhibition by nonnucleoside inhibitor ERDRP-0519

Abstract

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