Hantaviruses, transmitted primarily through rodents, represent a global health threat exacerbated by the absence of approved vaccines or treatments. The Andes virus, endemic to regions of the southwestern United States as well as parts of North and South America, has been responsible for severe outbreaks, including fatal infections such as the one reported last year in New Mexico. The research team’s detailed structural elucidation of the virus’s surface architecture is a foundational stride in battling these viruses before they spiral into widespread pandemics.

Central to the Andes virus’s infectivity is the Gn-Gc tetramer, a mushroom-shaped assembly of glycoproteins meticulously orchestrated on the viral surface. The team engineered virus-like particles—synthetic mimics devoid of viral genetic material—to safely analyze this complex. Employing cutting-edge cryo-electron microscopy (cryo-EM), which captures molecular shadows by transmitting electrons through vitrified samples, researchers reconstructed the Gn-Gc tetramers with unprecedented clarity. This technique exploits electron scattering to resolve molecular shapes at near-atomic scales.

A distinctive aspect of this study lies in the team’s novel approach to data refinement. They selectively isolated cryo-EM images of tetramers oriented perpendicular to the electron beam, while excluding other orientations. This selective curation allowed them to repurpose algorithmic reconstruction methods originally designed for isolated proteins rather than virus surface assemblies. The resulting 3D molecular maps feature an extraordinary resolution of 2.3 angstroms—fine enough to distinguish details on the scale of just a few atoms. This represents a quantum leap in structural precision compared to prior models resolving at approximately 12 angstroms, which were prone to inaccuracies.

The intricate details captured in this high-resolution structure reveal the conformational subtleties of the viral glycoprotein complex prior to cell attachment and fusion. This “pre-fusion” state is crucial for rational vaccine design because it informs how to stabilize the protein conformation so the immune system can recognize and neutralize the virus effectively. Once the virus initiates fusion with host cells, its surface proteins rearrange, rendering antibody targeting more challenging. The research team plans to leverage artificial intelligence-driven protein engineering to introduce stabilizing mutations that lock the tetramer in its vulnerable pre-fusion state, a strategy increasingly recognized as transformative in contemporary viral vaccine development.

The significance of this advance is underscored by the timing of NIH’s recent pandemic preparedness initiatives, which identified hantaviruses among the top viral families posing urgent pandemic risks. Funding channels through programs like ReVAMPP and the Provident consortium have catalyzed collaborative efforts, facilitating state-of-the-art structural studies and accelerating therapeutic innovation. The UT Austin team’s cross-institutional partnerships—with Texas A&M University, UT Southwestern Medical Center, and biotech firm HDT Bio—exemplify the integrative research model needed to confront emerging viral threats.

Notably, the team moved swiftly beyond characterization by engineering a vaccine candidate based on the high-resolution structural template. When administered to mice, this candidate elicited robust neutralizing antibody responses against the Andes virus, validating the functional utility of their structural findings. This success marks a milestone in translating nanoscale molecular insight into practical medical countermeasures that could one day reduce hantavirus mortality globally.

Beyond immediate vaccine implications, the methodology pioneered here—precise selection of favorable particle orientation coupled with advanced cryo-EM—promises broad applicability across virology. McLellan and colleagues anticipate that these techniques will empower researchers studying other challenging viral surface proteins, elevating our capacity to dissect and target viral architecture with surgical precision.

The team’s future trajectory involves both elucidating the structural dynamics of the Gn-Gc tetramers during infection and refining protein engineering approaches to enhance vaccine stability and efficacy. This dual focus integrates classical structural biology with avant-garde computational tools, reflecting a paradigm shift toward interdisciplinary strategies in infectious disease research.

In summary, this unprecedented high-resolution structural mapping of the Andes virus glycoprotein assembly unlocks new avenues for vaccine and antiviral development. As hantaviruses remain a looming pandemic threat with no current treatments, these insights represent a beacon of hope. By delineating the molecular blueprints of viral infection at near-atomic resolution, the researchers have provided the scientific community with powerful tools to design next-generation vaccines, neutralizing antibodies, and potentially antiviral drugs tailored to these deadly pathogens.

Subject of Research: Animals

Article Title: High-resolution in situ structures of hantavirus glycoprotein tetramers

News Publication Date: 27-Feb-2026

Web References:
DOI: 10.1016/j.cell.2026.01.030

References:
McLellan J.S., Guo L., et al. “High-resolution in situ structures of hantavirus glycoprotein tetramers,” Cell, 2026.

Image Credits: University of Texas at Austin

Keywords: Vaccine research, Hantavirus, Infectious diseases, Epidemics, Structural biology, Biomolecular structure

Leveraging a multidisciplinary approach that combines high-resolution cryo-electron microscopy with rigorous genetic, biochemical, and phylogenetic analyses, the study deciphers auxiliary structural components that endow C. jejuni’s motor with enhanced stability and torque-generation capacities. Central to their findings is the identification of a novel ‘E ring’ composed of 17 homodimers of the protein FlgY, which assembles circumferentially around the MS ring, a pivotal basal body structure. This E ring is not a mere architectural curiosity but appears critical for anchoring additional scaffolding proteins and stabilizing the entire rotary apparatus under the mechanical stresses of high-speed rotation.

In addition to the E ring, the researchers describe a sophisticated cage-like network involving proteins FcpM, FcpN, FcpO, and PflD. This cage forms an encompassing lattice around the motor’s stator complexes—energy transducing units responsible for torque generation. Intriguingly, these stator units are not randomly dispersed but preserved in a symmetric assembly coinciding with the unique 17-subunit E ring, suggesting a finely tuned coupling between these accessory components that maximizes motor efficiency and durability.

Bridging the E ring and the surrounding cage, the study highlights spoke–rim formations mediated by the interactions between PflA and PflB proteins. This structural spoke arrangement, mimicking a wheel’s spokes, strengthens the motor’s scaffolding network and further stabilizes the stator complexes. The extraordinary modularity and architectural complexity of these assemblies underscore evolutionary adaptations that likely confer enhanced motility advantages to C. jejuni in its ecological niches, where precise and powerful motility can mean the difference between colonization success and failure.

Moving beyond structural characterization, the team utilized phylogenetic methodologies to explore the evolutionary trajectory of these complex motor components. Their analyses reveal that the E ring and spoke structures are not anomalies but ancestral features with a surprisingly widespread distribution across diverse bacterial lineages. This suggests an ancient origin predating the divergence of multiple phyla—a finding that dramatically extends our understanding of flagellar motor evolution, beyond the oversimplified models based on enteric bacteria.

Moreover, the study uncovers compelling evidence for the evolutionary co-option of type IV pilus components into the flagellar motor machinery in the Campylobacterota phylum, to which C. jejuni belongs. This molecular repurposing event presumably equipped these bacteria with the elaborate scaffolds needed to support extraordinary torque and stability demands, highlighting an elegant example of evolutionary innovation through modular assembly and protein function reassignment.

The functional consequences of these complex motor architectures are profound. Compared to simpler bacterial motors, the C. jejuni motor can sustain higher torque output and rotational speeds, thereby enhancing its chemotactic abilities under diverse environmental challenges. These adaptive benefits possibly underpin the pathogenic success of C. jejuni, which relies on aggressive motility to traverse mucus layers and establish infection within host organisms.

From a structural biology perspective, the revelation of 17-fold symmetry in FlgY homodimer arrangements and their direct physical and functional linkages to other motor elements pushes the envelope in molecular microbial nanomachinery. It challenges previously held notions regarding the stoichiometric and spatial organization of flagellar motor complexes and invites re-examination of torque generation mechanisms under novel structural constraints.

The interdisciplinary strategy adopted in this investigation exemplifies how integrated structural, genetic, and computational tools can uncover hidden complexities in well-known biological machines. The synergy of advanced cryo-EM imaging with detailed protein interaction assays, coupled with evolutionary genomics, constructs a vivid narrative of both the assembly and the long evolutionary dance that sculpted the C. jejuni flagellar motor into its present form.

This study also raises intriguing questions about the dynamics and regulation of such complex flagellar systems. For example, how do the multiple interacting scaffolds assemble in vivo during flagellar biogenesis, and what molecular signals coordinate the integration of these auxiliary components with core motor elements? Understanding these processes could pave the way for the development of novel antibacterial strategies aimed at disrupting motility — a key factor in bacterial pathogenesis.

Beyond microbiology, these findings inspire biomimetic engineering pursuits. The sophisticated organization and interplay of modular scaffolds in flagellar motors embody principles of nanoscale mechanical design that could inform the creation of synthetic nanomachines or microrobots, offering revolutionary applications in medicine and technology.

This comprehensive structural elucidation of Campylobacter’s complex flagellar motor thus represents a paradigm shift, blending evolutionary biology with cutting-edge molecular insights while laying fertile ground for translational innovations. As the field progresses, further exploration of bacterial flagellar diversity promises to unlock even deeper understanding of microbial motility, adaptation, and evolution.

In conclusion, the work spearheaded by Feng, Tachiyama, He, and colleagues delivers an unprecedented window into the structural sophistication and evolutionary ingenuity of bacterial flagellar motors, especially within the enigmatic Campylobacterota lineage. By delineating the roles of novel scaffold components and their integration into highly symmetric molecular assemblies, the study enriches a classic model with fresh complexity and evolutionary perspective. It is a compelling reminder that the microscopic engines driving bacterial life remain a continual source of scientific wonder and technological inspiration.

Subject of Research: Structural, functional and evolutionary characterization of complex bacterial flagellar motors in Campylobacter jejuni.

Article Title: Structural insights into the assembly and evolution of a complex bacterial flagellar motor.

Article References:
Feng, X., Tachiyama, S., He, J. et al. Structural insights into the assembly and evolution of a complex bacterial flagellar motor. Nat Microbiol (2026). https://doi.org/10.1038/s41564-025-02248-5

Image Credits: AI Generated

DOI: https://doi.org/10.1038/s41564-025-02248-5

Glycoprotein B, a key viral envelope protein, is indispensable for herpesvirus entry into host cells, mediating membrane fusion during viral infection. Its dynamic structural rearrangements, shifting between prefusion and postfusion conformations, have historically complicated efforts to design effective inhibitors. Researchers have now illuminated this challenging target by isolating a nanobody, Nb1_gbHSV, that exhibits a striking preference for the prefusion form, a conformation transiently adopted during the virus’s entry process.

High-resolution cryo-electron microscopy of gB bound by Nb1_gbHSV revealed a detailed interaction landscape. The nanobody engages simultaneously with three distinct domains on gB, namely Di, Diii, and Div. This multifunctional engagement is stabilised through an extraordinary network of 23 hydrogen bonds and eight salt bridges, resulting in an extensive buried surface area measuring approximately 1,260 Ų. Such intimate molecular interactions underscore the nanobody’s formidable binding affinity.

Residue R102 on Nb1_gbHSV plays a pivotal role, protruding into the interface between Div and Di to form additional hydrogen bonds with Di and Diii of the same protomer. This precise targeting is significant because Di and Div reside in proximity only in the prefusion conformation; in the postfusion state, these domains are widely separated. Consequently, the nanobody’s epitope is structurally accessible solely in the prefusion form, conferring a remarkable degree of conformation specificity.

Functional assays substantiated the nanobody’s selective affinity, with microscale thermophoresis revealing a dissociation constant (KD) around an extraordinarily low 14 picomolar for prefusion gB, whereas no measurable binding occurred with the postfusion form. This demonstrates the nanobody’s potential to act as a prefusion-specific antagonist, a critical advantage as viral fusion proteins often evade neutralization by transitioning to postfusion states.

Cross-reactivity assays provided further excitement, as Nb1_gbHSV was found to bind gB from both HSV-1 and HSV-2. Despite low conservation of the epitope among other human-infecting herpesviruses such as varicella-zoster virus (VZV), cytomegalovirus (HCMV), and Epstein-Barr virus (EBV), the nanobody’s binding to HSV-2 gB is likely underpinned by the high sequence similarity in this region between HSV-1 and HSV-2. This cross-species reactivity enhances the therapeutic promise of Nb1_gbHSV.

Cellular localization experiments using fluorescently labelled Nb1_gbHSV confirmed the nanobody’s ability to bind gB expressed on the plasma membrane of transfected baby hamster kidney (BHK-21) cells. Co-localization with green fluorescent protein tags on gB reinforced these findings, with evidence suggesting rapid internalization of the nanobody-gB complex via endocytosis. This internal trafficking indicates the nanobody does not interrupt native cellular machinery, a critical consideration for therapeutic applications that require minimal off-target effects.

Structural modeling further supports the prefusion-specific nature of Nb1_gbHSV. When computationally docked onto the postfusion conformation of gB, the nanobody induces steric clashes between domains, particularly Div and Di of adjacent protomers, implicating an unstable interaction. This implies that Nb1_gbHSV likely stabilizes the prefusion form, preventing the conformational changes necessary for viral membrane fusion, thus neutralizing viral infectivity.

This discovery marks a significant milestone in the development of nanobody-based therapeutics against herpesviruses. Nanobodies, due to their small size and stability, offer distinct advantages over conventional antibodies, including higher tissue penetration and ease of manufacturing. The selective targeting of a metastable prefusion state presents a compelling antiviral approach, potentially limiting viral spread and ameliorating disease severity.

Moreover, the detailed characterization of the Nb1_gbHSV binding interface opens avenues for rational drug design. Small molecules or engineered biologics mimicking this interface could be developed to enhance the antiviral arsenal against herpesviruses. Additionally, the unique epitopic site defined by the proximity of Di and Div domains provides a blueprint for future vaccines aimed at eliciting broadly neutralizing antibodies against HSV-1 and HSV-2.

The research also underscores the importance of nanobody technology in virology. By exploiting their unique binding modalities and conformational selectivity, nanobodies can illuminate viral protein dynamics and provide effective means to disrupt viral life cycles. Nb1_gbHSV exemplifies this potential, evidencing high specificity without compromising cellular functions such as endocytosis, a balance essential for safe therapeutic application.

As HSV remains a significant global health burden — with tens of millions affected worldwide, and complications ranging from painful mucocutaneous lesions to neuroinvasive diseases — the emergence of such innovative molecular tools is urgently needed. Nb1_gbHSV’s ability to differentiate viral conformations and cross-react with multiple HSV species suggests a versatile template for future antiviral therapies that could surpass current treatment limitations.

Continuing structural and functional analyses are anticipated to further clarify the mechanisms by which Nb1_gbHSV exerts viral neutralization in vivo. Future studies will also explore its therapeutic efficacy, pharmacodynamics, and potential integration into clinical regimens. The promise of neutralizing gB at its prefusion conformation heralds a new frontier for vaccines and biologics against herpes simplex viruses.

In summary, Nb1_gbHSV represents a transformative breakthrough in herpesvirus research, epitomizing the intersection of structural biology, immunology, and nanobody engineering. By harnessing prefusion specificity and cross-species reactivity, this molecule exemplifies next-generation antiviral strategies poised to mitigate the global impact of HSV infections.

Subject of Research: Nanobody-mediated neutralization of herpes simplex virus glycoprotein B prefusion conformation

Article Title: A nanobody specific to prefusion glycoprotein B neutralizes HSV-1 and HSV-2

Article References:
Vollmer, B., Ebel, H., Rees, R. et al. A nanobody specific to prefusion glycoprotein B neutralizes HSV-1 and HSV-2. Nature (2025). https://doi.org/10.1038/s41586-025-09438-5