Structural determinants of TRPV4 inhibition and identification of new antagonists with antiviral activity.

ABSTRACT:

Background and purpose

The transient receptor potential vanilloid 4 (TRPV4) cation channel participates in multiple physiological processes and is also at the core of different diseases, making this channel an interesting pharmacological target with therapeutic potential. However, little is known about the structural elements governing its inhibition.

Experimental approach

We have now combined in silico drug discovery and molecular dynamics simulation based on Xenopus tropicalis xTRPV4 structure with functional studies measuring cell Ca²⁺ influx mediated by human TRPV4 channel to characterize the binding site of known TRPV4 inhibitors and to identify novel small molecule channel modulators.

Key results

We have found that the inhibitor HC067047 binds to a po

SUBMITTER: Donate-Macian P 

PROVIDER: S-EPMC9291951 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature