Eigen RadarScience
Archive
Analysis

Three drug copies on one carrier clump influenza particles

A cell and mouse paper joined flu drugs to an antibody fragment so one molecule carries three copies. The three-copy zanamivir form, AVC-Z3, made virus particles clump, which hindered both cell entry and later release. A three-copy peramivir form, AVC-P3, was stronger in cells. In mice its half-life outran AVC-Z3 and also the YTE version of CD388, and showed a stronger effect than baloxavir and CD388 in mice given H1N1, H3N2, H5N1 or influenza B. The measurements stop at cells and mice.

Science··Midday
A researcher in navy scrubs checks a transparent enclosure holding three white mice on a bright laboratory cage rack.

Three zanamivir copies clump the particles

The chemists clicked a single copy, a pair, or a trio of the same flu drug onto the Fc fragment of an antibody. Zanamivir was the first drug in that series. The three-copy form, called AVC-Z3, was more active in cells than the one-copy and two-copy forms. AVC-Z3 drew separate virus particles into clusters. Clustered particles were poorer at entering a cell and poorer at leaving one afterwards.[1]

The clump is a physical hold, set beside the drug’s ordinary action on neuraminidase. The authors treat the copy count as the feature that changes how the molecule behaves. CD388, an earlier long-acting drug-Fc conjugate aimed at influenza A and influenza B, is the molecule they measure the new series against.[1]

Peramivir’s three-copy form lasted longer in mice

The same carrier was then loaded with peramivir. AVC-P3, the three-copy peramivir form, was stronger in cells than AVC-Z3. In mice the half-life of AVC-P3 outran both AVC-Z3 and CD388 once that older conjugate carried a YTE mutation.[1]

The mouse infections used H1N1, H3N2, H5N1 and influenza B. Across those four, AVC-P3 showed a stronger antiviral effect than the other conjugates in the series, than baloxavir, and than CD388. That ranking belongs to these mouse infections.[1]

The ranking stops at the mouse infections

Every head-to-head comparison in the paper is a cell assay or a mouse infection. A mouse given a lab strain is a narrow stand-in for a person with seasonal flu, and the paper includes no human dosing result. What is in hand is one peer-reviewed chemistry-and-animal study of copy number, clumping and those four mouse infections.[1]

References

  1. News sourceNature CommunicationsThree-copy flu-drug conjugates clump virus particles in mice↩1↩2↩3↩4↩5
Space and explorationEnergy transition and climate

More analysis from this desk

View all Brief analyses from the Science desk →