# The Potential of Cyclodextrins as Inhibitors for the BM2 Protein: An In Silico Investigation

## TL;DR

This study explores how cyclodextrins might block a key influenza virus protein, potentially leading to new antiviral treatments.

## Contribution

The novel hypothesis that cyclodextrins can inhibit the BM2 proton channel of influenza virus is tested using molecular dynamics simulations.

## Key findings

- CD4, CD5, and CD6 bind to the BM2TM proton channel and disrupt water networks essential for proton conduction.
- CD4 completely obstructs the BM2TM water channel, showing the strongest inhibitory potential.
- Hydrogen bond occupancy between H19 and solvent in the BM2TM channel is reduced by cyclodextrin binding.

## Abstract

The influenza BM2 transmembrane domain (BM2TM), an acid-activated proton channel, is an attractive antiviral target due to its essential roles during influenza virus replication, whereas no effective inhibitors have been reported for BM2. In this study, we draw inspiration from the properties of cyclodextrins (CDs) and hypothesize that CDs of appropriate sizes may possess the potential to act as inhibitors of the BM2TM proton channel. To explore this possibility, molecular dynamics simulations were employed to assess their inhibitory capabilities. Our findings reveal that CD4, CD5, and CD6 are capable of binding to the BM2TM proton channel, resulting in disrupted water networks and reduced hydrogen bond occupancy between H19 and the solvent within the BM2TM channel necessary for proton conduction. Notably, CD4 completely obstructs the BM2TM water channel. Based on these observations, we propose that CD4, CD5, and CD6 individually contribute to diminishing the proton transfer efficiency of the BM2 protein, and CD4 demonstrates promising potential as an inhibitor for the BM2 proton channel.