# Identification of a Non-Retinoid Opsin Ligand Through Pharmacophore-Guided Virtual Screening—A Novel Potential Rhodopsin-Stabilizing Compound

## TL;DR

Researchers identified a new compound that could stabilize rhodopsin, a protein involved in vision, potentially offering a safer treatment for retinal diseases.

## Contribution

A novel non-retinoid ligand for opsin was discovered through virtual screening and validated as a potential pharmacological chaperone.

## Key findings

- A pharmacophore-guided virtual screening identified a non-retinoid compound that binds opsin.
- VS1 was confirmed to bind opsin and could serve as a starting point for stabilizer development.
- The compound offers a safer alternative to retinoid-based chaperones with fewer toxicity issues.

## Abstract

Rhodopsin, a G-protein-coupled receptor (GPCR) comprising the protein opsin covalently linked to the chromophore 11-cis retinal, is pivotal in visual phototransduction. Mutations in the gene encoding rhodopsin (RHO) can cause opsin misfolding or reduce its stability, resulting in retinal degenerative disorders such as retinitis pigmentosa (RP). Current therapeutic strategies employing retinoid-based chaperones partially rescue the folding and trafficking of mutant rhodopsin, but are limited by inherent toxicity and instability due to photoinduced isomerization. In the present work, a pharmacophore-based virtual screening protocol combined with molecular docking and molecular dynamics simulations was employed, leading to the identification of a novel non-retinoid opsin ligand that can potentially act as a pharmacological chaperone. Biological validation confirmed that the compound VS1 binds opsin effectively, representing a valuable starting point for structure-based optimization studies aimed at identifying new opsin stabilizers.