Researchers at Umeå University have identified two human nuclear pore complex proteins, NUP98 and NUP153, as key host factors that facilitate replication of orthoflaviviruses, including tick-borne encephalitis virus, West Nile virus, and dengue virus.

The findings challenge existing views on how flaviviruses hijack host cells and lay the groundwork for antiviral drugs that target host factors rather than viral components.

By focusing on stable host proteins like nucleoporins, the study suggests potential for broad-spectrum and more resilient antivirals with reduced risk of viral resistance.

The research marks a paradigm shift by showing nucleoporins play active roles in cytosolic viral replication, opening new avenues for host–virus interaction–focused therapeutics.

A collaboration with Uppsala University identified a synthetic peptide that blocks NUP98’s binding to viral RNA, dramatically reducing viral replication and signaling a viable host-factor–targeted antiviral strategy.

The work was published in Nature Communications on April 8, 2026, led by Anna Överby Wernstedt and colleagues from Umeå University, with Uppsala University as a collaborator.

The study emphasizes interdisciplinary approaches and supports pursuing host-factor–based antiviral designs to combat flavivirus diseases globally.

NUP98 is required for efficient replication of viral RNA, while NUP153 modulates viral protein production by binding a specific region of viral RNA between structural and non-structural coding sequences, aiding early infection.

During infection, NUP98 and NUP153 relocate from nuclear pores to cytosolic viral replication sites and may interact with viral RNA and proteins to regulate replication.

NUP153’s binding to the RNA region between structural and non-structural sequences helps fine-tune viral protein expression, crucial at early infection stages.

The research points toward broader antiviral potential by targeting host factors like NUP98 and NUP153 rather than rapidly mutating viral targets, potentially reducing resistance.