SCIENTISTS have revealed how New World hantaviruses recognise a human cell receptor, providing structural insights that could support the development of future antiviral treatments.
Hantaviruses are rodent-borne pathogens that can cause severe disease in humans, yet no approved therapeutics are available. New World hantaviruses, including Andes virus (ANDV), use the cell-surface receptor protocadherin-1 (PCDH1) to enter host cells. However, the structural basis of this interaction has remained unclear.
The study, published in Nature, describes the structure of PCDH1 bound to the ANDV spike at near-atomic resolution, clarifying how the virus engages its receptor.
The researchers found that PCDH1 binds asymmetrically within a deep central pocket formed by four Gn protomers in the viral spike. This recessed binding site helps explain why PCDH1 recognises only intact viral particles or soluble tetramers, rather than isolated components.
The findings identify a structural strategy through which hantaviruses can conceal their receptor-binding site within a depression on the viral surface. Understanding this arrangement provides insight into how the virus establishes the interaction needed for cell entry.
Mutagenesis experiments identified three Gn loops that shape the receptor-binding site. The researchers also demonstrated that these structural features can enable PCDH1 binding to be transferred from New World to Old World hantavirus glycoproteins.
These findings help define the viral features responsible for receptor recognition and offer a clearer understanding of the structural determinants governing interactions between hantaviruses and host cells.
Structural and functional analyses of four neutralising antibodies revealed two distinct mechanisms for blocking receptor binding. Some antibodies occluded access to the PCDH1-binding site, while others prevented receptor engagement through steric interference.
Together, these results explain how antibodies can counter the virus’s recessed receptor-binding strategy. The structural framework established by the study could inform the design of antiviral therapeutics that target the hantavirus spike, addressing an important gap in treatment options for these potentially severe infections.
Although the findings provide a foundation for future therapeutic development, further work will be needed to translate these structural insights into effective treatments.
Reference
Battini L et al. Structural basis for protocadherin-1 recognition by New World hantaviruses. Nature. 2026. [Epub ahead of print].
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