Structural Studies of RNA Virus Replication

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Virology".

Deadline for manuscript submissions: 31 October 2026 | Viewed by 2176

Editor


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Guest Editor
1. Department of Chemistry, Georgia State University, Atlanta, GA 35302, USA
2. Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 35302, USA
Interests: influenza virus; respiratory viruses; biochemistry; biophysical chemistry

Special Issue Information

Dear Colleagues,

RNA viruses include a large number of pathogens infecting humans, animals and plants. They cause serious problems for human health and economics. Since the genome of these viruses is RNA, special mechanisms of RNA replication are encoded by the viral genome, which is not present in the host cell. The first step in the cycle of virus replication is entry of the host cell. Upon cell entry, viral proteins are produced and the RNA genome is amplified by the viral mechanism. Different RNA viruses may use different mechanisms to produce viral proteins. In positive strand RNA viruses, the viral genome may be directly translated by host ribosomes to synthesize viral proteins. In negative strand and double-stranded RNA viruses, mRNAs are first transcribed from the viral genome, followed by translation by host ribosomes. New virions are assembled to package the RNA genome by viral proteins to carry on further infection. There are extensive structural studies of each step in virus replication. They reveal the molecular details for these biochemical activities. These research efforts greatly facilitate the development of antiviral drugs and vaccines, which brings unprecedented benefits to our life.

Prof. Dr. Ming Luo
Guest Editor

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Keywords

  • crystal
  • cryoEM
  • cryoET
  • genome
  • polymerase
  • replication
  • transcription
  • RNA synthesis
  • assembly
  • entry

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Published Papers (3 papers)

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Research

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9 pages, 1640 KB  
Communication
Differences in RNA Binding Between Segmented and Non-Segmented Negative-Strand Virus Nucleocapsids
by Rob W. H. Ruigrok, Allison Ballandras-Colas, Thibaut Crépin, Hélène Malet and Dan Kolakofsky
Microorganisms 2026, 14(6), 1194; https://doi.org/10.3390/microorganisms14061194 - 26 May 2026
Viewed by 550
Abstract
Segmented and non-segmented negative-strand RNA viruses share the same general pathway for genome transcription, which generates messenger RNA, and genome replication which duplicates the viral RNA. These processes are performed by the viral polymerase and necessitate the viral RNA to be coated by [...] Read more.
Segmented and non-segmented negative-strand RNA viruses share the same general pathway for genome transcription, which generates messenger RNA, and genome replication which duplicates the viral RNA. These processes are performed by the viral polymerase and necessitate the viral RNA to be coated by a non-covalent polymer of nucleoproteins known as nucleocapsid. The non-segmented negative-strand RNA viruses (nsNSVs) have rigid nucleocapsids covering the entire tightly bound genome and require a phosphoprotein cofactor for proper replication and transcription by the polymerase, while the segmented negative-strand RNA viruses (sNSVs) have very flexible nucleocapsids with only few nucleotides tightly bound to each nucleoprotein, and their viral RNA genome ends are directly bound to the polymerase. We discuss here how the differences in RNA binding are likely to be crucial for proper replication and transcription in both nsNSVs and sNSVs. Full article
(This article belongs to the Special Issue Structural Studies of RNA Virus Replication)
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15 pages, 2869 KB  
Article
Assembly of the Linear Viral Nucleocapsid
by Ming Luo, Kristin V. Lyles, Oluwafoyinsola O. Faniyi and Ryuha Kim
Microorganisms 2026, 14(4), 848; https://doi.org/10.3390/microorganisms14040848 - 9 Apr 2026
Viewed by 680
Abstract
Nucleocapsids protect viral genomes and play fundamental roles in viral assembly and infection. While many viruses adopt icosahedral or helical symmetries, negative-strand RNA viruses (NSVs) assemble their nucleocapsids with a distinct translation-based symmetry that is often considered helical because of their curvature. Our [...] Read more.
Nucleocapsids protect viral genomes and play fundamental roles in viral assembly and infection. While many viruses adopt icosahedral or helical symmetries, negative-strand RNA viruses (NSVs) assemble their nucleocapsids with a distinct translation-based symmetry that is often considered helical because of their curvature. Our study analyzes the structural basis, assembly principles, and functional implications of the linear nucleocapsids. Structural coordinates of viruses were obtained from the Protein Data Bank (PDB) and examined using PyMOL version 1.3 to compare protein folds, RNA–protein interactions, inter-subunit contacts, and curvature properties across multiple nucleocapsids. We found that linear nucleocapsids share a similar 5H + 3H fold in their capsid proteins and encapsidate a fixed number of nucleotides per subunit, though the degree of nucleotide sequestration varies. Their architecture differs in inter-subunit interactions, determining whether empty capsids can assemble and influencing RNase sensitivity. Although these nucleocapsids may appear helical, they lack strict helical symmetry and instead display variable curvature that is modulated by environmental conditions. Relaxation of this curvature is likely required for viral RNA-dependent RNA polymerase to access the sequestered RNA genome during transcription/replication. In conclusion, linear nucleocapsids constitute a class of RNA–protein assemblies with variable curvature. The topologically conserved fold of the capsid protein enables genome protection while regulating exposure of RNA during viral RNA synthesis. Full article
(This article belongs to the Special Issue Structural Studies of RNA Virus Replication)
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Review

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22 pages, 3704 KB  
Review
Structural Advances in Respiratory Syncytial Virus: Implications for Vaccine and Antiviral Development
by Xuanwei Huang, Caner Akıl and Peijun Zhang
Microorganisms 2026, 14(5), 1130; https://doi.org/10.3390/microorganisms14051130 - 16 May 2026
Cited by 2 | Viewed by 578
Abstract
Respiratory syncytial virus (RSV) remains a leading cause of severe lower respiratory tract disease in infants, older adults, and immunocompromised individuals. Over the past decade, advances in structural biology, particularly cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET), have transformed our understanding of RSV [...] Read more.
Respiratory syncytial virus (RSV) remains a leading cause of severe lower respiratory tract disease in infants, older adults, and immunocompromised individuals. Over the past decade, advances in structural biology, particularly cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET), have transformed our understanding of RSV architecture, dynamics, and the mechanisms of entry and replication. High-resolution structures of the prefusion F glycoprotein (pre-F) and its complexes with neutralizing antibodies established the rationale for structure-guided antigen stabilization and directly enabled the development of the first licensed RSV vaccines. Complementary structures of the ribonucleoprotein, polymerase complex, and matrix lattice have broadened therapeutic targets beyond F. Here, we summarize these structural advances; review current structure-guided vaccine, antibody, and antiviral development efforts; and highlight priorities for next-generation vaccines and therapeutics. Full article
(This article belongs to the Special Issue Structural Studies of RNA Virus Replication)
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