ArticleNature microbiology2021
Cryo-EM structures of Lassa and Machupo virus polymerases complexed with cognate regulatory Z proteins identify targets for antivirals.
Article in Nature microbiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- Structure of Crimean-Congo haemorrhagic fever virus RNA polymerase.Nature microbiology · 2026Article
- Characterization of conserved residues in the mammarenavirus matrix protein Z using novel Lassa virus life cycle modelling assays.Scientific reports · 2026Article
- Targeting the Rift Valley Fever Virus Polymerase: Resistance Mechanisms and Structural Insights.ACS infectious diseases · 2025Article
- Identification of Factors Contributing to Pathogenic Variability Among Lassa Virus Strains Using the Guinea Pig Model and Reverse Genetics.The Journal of infectious diseases · 2025Article
- Article
- Structural basis for the activation of plant bunyavirus replication machinery and its dual-targeted inhibition by ribavirin.Nature plants · 2025Article
- Lassa virus protein-protein interactions as mediators of Lassa fever pathogenesis.Virology journal · 2025Review
- Targeting n-myristoyltransferases promotes a pan-Mammarenavirus inhibition through the degradation of the Z matrix protein.PLoS pathogens · 2024Article
- Lassa virus Z protein hijacks the autophagy machinery for efficient transportation by interrupting CCT2-mediated cytoskeleton network formation.Autophagy · 2024Article
- Unraveling factors responsible for pathogenic differences in Lassa virus strains.bioRxiv : the preprint server for biology · 2024Article
- Treatment of highly virulent mammarenavirus infections-status quo and future directions.Expert opinion on drug discovery · 2024Review
- Spatio-temporal spread and evolution of Lassa virus in West Africa.BMC infectious diseases · 2024Article
- Structural characterization of the oligomerization of full-length Hantaan virus polymerase into symmetric dimers and hexamers.Nature communications · 2024Article
- Development of reverse genetics system for Guanarito virus: substitution of E1497K in the L protein of Guanarito virus S-26764 strain changes plaque phenotype and growth kinetics.Journal of virology · 2024Article
- RNA to Rule Them All: Critical Steps in Lassa Virus Ribonucleoparticle Assembly and Recruitment.Journal of the American Chemical Society · 2023Article
- The Arenaviridae Family: Knowledge Gaps, Animal Models, Countermeasures, and Prototype Pathogens.The Journal of infectious diseases · 2023Article
- Article
- Fine Regulation of Influenza Virus RNA Transcription and Replication by Stoichiometric Changes in Viral NS1 and NS2 Proteins.Journal of virology · 2023Article
- Fundamentals of HDX-MS.Essays in biochemistry · 2023Review
- The mechanism of genome replication and transcription in bunyaviruses.PLoS pathogens · 2023Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Zoonotic arenaviruses can lead to life-threating diseases in humans. These viruses encode a large (L) polymerase that transcribes and replicates the viral genome. At the late stage of replication, the multifunctional Z protein interacts with the L polymerase to shut down RNA synthesis and initiate virion assembly. However, the mechanism by which the Z protein regulates the activity of L polymerase is unclear. Here, we used cryo-electron microscopy to resolve the structures of both Lassa and Machupo virus L polymerases in complex with their cognate Z proteins, and viral RNA, to 3.1-3.9 Å resolutions. These structures reveal that Z protein binding induces conformational changes in two catalytic motifs of the L polymerase, and restrains their conformational dynamics to inhibit RNA synthesis, which is supported by hydrogen-deuterium exchange mass spectrometry analysis. Importantly, we show, by in vitro polymerase reactions, that Z proteins of Lassa and Machupo viruses can cross-inhibit their L polymerases, albeit with decreased inhibition efficiencies. This cross-reactivity results from a highly conserved determinant motif at the contacting interface, but is affected by other variable auxiliary motifs due to the divergent evolution of Old World and New World arenaviruses. These findings could provide promising targets for developing broad-spectrum antiviral drugs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.