Discovery of Clioquinol and analogues as novel inhibitors of Severe Acute Respiratory Syndrome Coronavirus 2 infection, ACE2 and ACE2 - Spike protein interaction in vitro
Omonike A. Olaleye, Manvir Kaur, Collins Onyenaka, Tolulope Adebusuyi
Abstract
all three compounds showed potent anti-exopeptidase activity against recombinant human angiotensin-converting enzyme 2 (rhACE2) and inhibited the binding of rhACE2 with SARS-CoV-2 Spike (RBD) protein. CLQ displayed the highest potency in the low micromolar range, with its antiviral activity showing a strong correlation with inhibition of rhACE2 and rhACE2-RBD interaction. Altogether, our findings provide a new mode of action and molecular target for CLQ and validates this pharmacophore as a promising lead series for the clinical development of potential therapeutics for COVID-19.
Topics & Concepts
ClioquinolCoronavirusPharmacologyDrugIn vitroPotencyMiddle East respiratory syndrome coronavirusPharmacophoreChemistryDrug repositioningVirologyMedicineCoronavirus disease 2019 (COVID-19)BiochemistryDiseaseInfectious disease (medical specialty)Internal medicineSARS-CoV-2 and COVID-19 ResearchComputational Drug Discovery MethodsCOVID-19 Clinical Research Studies