Discovery of new Schistosoma mansoni aspartyl protease inhibitors by structure-based virtual screening.

ABSTRACT:

Background

Schistosomiasis is a neglected tropical disease caused by trematodes of the genus Schistosoma, with a limited treatment, mainly based on the use of praziquantel (PZQ). Currently, several aspartic proteases genes have already been identified within the genome of Schistosoma species. At least one enzyme encoded from this gene family (SmAP), named SmCD1, has been validated for the development of schistosomicidal drugs, since it has a key role in haemoglobin digestion by worms.

Objective

In this work, we integrated a structure-based virtual screening campaign, enzymatic assays and adult worms ex vivo experiments aiming to discover the first classes of SmCD1 inhibitors.

Methods

Initially, the 3D-structures of SmCD1, SmCD2 and SmCD3 were generated using homology

SUBMITTER: Gomes BF 

PROVIDER: S-EPMC10481938 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature