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Pharmacophore Virtual Screening Identifies Riboflavin as an Inhibitor of the Schistosome Cathepsin B1 Protease with Antiparasitic Activity. | LitMetric

Pharmacophore Virtual Screening Identifies Riboflavin as an Inhibitor of the Schistosome Cathepsin B1 Protease with Antiparasitic Activity.

ACS Omega

Grupo de Pesquisas Químico-Farmacêuticas da Unifesp, Department of Pharmaceutical Sciences Rua São Nicolau, Universidade Federal de São Paulo-Campus Diadema, 210, 2o andar, Centro, Diadema, São Paulo 09972-270, Brazil.

Published: June 2024

AI Article Synopsis

  • Schistosomiasis is a disease affecting over 200 million individuals globally, traditionally treated with a single drug, but research is focused on finding new treatments targeting the SmCB1 enzyme.
  • A structure-based pharmacophore virtual screening identified riboflavin (RBF) as a promising antischistosomal agent, which showed significant results in both lab tests and animal models.
  • In a murine model, RBF reduced worm loads by about 20% and significantly lowered intestinal and fecal egg counts by approximately 80% after just one week of treatment.

Article Abstract

Schistosomiasis is a neglected disease of poverty that affects over 200 million people worldwide and relies on a single drug for therapy. The cathepsin B1 cysteine protease (SmCB1) of has been investigated as a potential target. Here, a structure-based pharmacophore virtual screening (VS) approach was used on a data set of approved drugs to identify potential antischistosomal agents targeting SmCB1. Pharmacophore (PHP) models underwent validation through receiver operating characteristics curves achieving values >0.8. The data highlighted riboflavin (RBF) as a compound of particular interest. A 1 μs molecular dynamics simulation demonstrated that RBF altered the conformation of SmCB1, causing the protease's binding site to close around RBF while maintaining the protease's overall integrity. RBF inhibited the activity of SmCB1 at low micromolar values and killed the parasite in vitro. Finally, in a murine model of infection, oral administration of 100 mg/kg RBF for 7 days significantly decreased worm burdens by ∼20% and had a major impact on intestinal and fecal egg burdens, which were decreased by ∼80%.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11170711PMC
http://dx.doi.org/10.1021/acsomega.4c03376DOI Listing

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