Apr 14, 2020

Sphingolipid Biosynthesis Inhibition As A Host Strategy Against Diverse Pathogens

BioRxiv : the Preprint Server for Biology
S. KumarTimothy R Peterson

Abstract

Chloroquine is an anti-malarial and immunosuppressant drug that has cationic amphipathic chemical properties. We performed genome-wide screens in human cells with chloroquine and several other widely used cationic amphipathic drugs (CADs) including the anti-depressants, sertraline (Zoloft) and fluoxetine (Prozac), the analgesic nortriptyline (Pamelor), the anti-arrhythmic amiodarone (Cordarone), and the anti-hypertensive verapamil (Calan) to characterize their molecular similarities and differences. Despite CADs having different disease indications but consistent with them sharing key chemical properties, we found CADs to have remarkably similar phenotypic profiles compared with non-CADs we and others have previously screened. The most significant genetic interaction for all CADs was the initiating step in sphingolipid biosynthesis catalyzed by serine palmitoyltransferase (SPT). A comparison of genome-wide screens performed with diverse pathogens from viruses, bacteria, plants, and parasites including Ebola, adeno-associated virus AAV2, HIV, Rotavirus, Influenza A, Zika virus, Picornavirus, Exotoxin A, Cholera toxin, Type III secretion system and Shiga toxin, Ricin toxin, and Toxoplasma gondii showed SPT as a top common host fa...Continue Reading

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Mentioned in this Paper

Vessels; Occlusion
Treatment Protocols
Research
Medication Management
Clinical Trials, Randomized
Medical Devices
SMART 100
Acute Cerebrovascular Accidents
Thrombectomy
Cerebrovascular Accident

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