Pocapavir binds an oligomeric poliovirus capsid composed of 60 subunits. Mutations can change this subunit's shape and prevent binding. However, if capsids contain both susceptible AND resistant subunits, drug can bind anyway. As a result, sus viruses can sensitize res ones when they share a cell.

In theory, this means that sus viruses should prevent resistance from spreading intra-host while it's rare. Does it work? @alexrob.bsky.social built a poliovirus replication model to probe the impact of intra-cellular resource sharing, and validated it against experimental and clinical data.

The answer? Sometimes! The key variable is the density of the viral population. When viruses coinfect often, interference is effective at arresting resistance evolution. BUT, if the drug works well, it reduces viral density, ultimately allowing resistance to escape this interference.

Understanding this feedback could allow us to design more evolution-proof therapies by maintaining therapeutically useful social interactions over time. @alexrob.bsky.social finds that neutralizing fewer viruses with weaker drugs can paradoxically lead to less resistance and lower viral loads.

This parallels ongoing work in the treatment of cancers and bacteria showing that competitive inhibition and ecological interaction mediated by drug dosing can improve population control.

Please check out the paper for our full results, and this nice press release put out by @uwnews.uw.edu! newsroom.uw.edu/news-release...