| Autor: |
Margot Lautens, Serrat X, Andrew G. Fraser, June H. Tan, Samantha Del Borrello, Michael R Schertzberg |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.1101/2021.03.24.436840 |
| Popis: |
Soil transmitted helminths (STHs) are major human pathogens that infect over a billion people. Resistance to current anthelmintics is rising and new drugs are needed. Here we combine multiple approaches to find druggable targets that are essential for RQ-dependent metabolism, an unusual form of anaerobic metabolism which STHs need to survive in their host. We identified 25 genes predicted to act in RQ-dependent metabolism from sensing hypoxia to RQ synthesis — this includes components of the kynurenine pathway we previously showed to be essential for RQ synthesis (Del Borrello et al., 2019). We found 9 genes to be required — since all have host orthologues, we used comparative genomics and structural modeling to identify those with helminth-specific active sites and found 4 such targets. These 4 high confidence targets open up the possibility of in silico screens to identify STH-specific inhibitors of these enzymes as new anthelmintics. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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