Discovery of Clioquinol and analogues as novel inhibitors of Severe Acute Respiratory Syndrome Coronavirus 2 infection, ACE2 and ACE2 - Spike protein interaction in vitro

• DOI: 10.1016/j.heliyon.2021.e06426
• Publication Date: 2021-03-12T11:53:54Z
• Authors: Omonike A. Olaleye; Manvir Kaur; Collins Onyenaka; Tolulope Adebusuyi
• Keywords: Clioquinol; Coronavirus; Drug repositioning

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent for coronavirus disease 2019 (COVID-19), has resulted in an ongoing pandemic. Presently, there are no clinically approved drugs COVID-19. Hence, is urgent need to accelerate development of effective antivirals. Herein, we discovered Clioquinol (5-chloro-7-iodo-8-quinolinol (CLQ)), a Food and Drug Administration (FDA) drug, two its analogues (7-bromo-5-chloro-8-hydroxyquinoline (CLBQ14); 5, 7-Dichloro-8-hydroxyquinoline (CLCQ)) as potent inhibitors SARS-CoV-2 infection-induced cytopathic effect vitro. In addition, all three compounds showed anti-exopeptidase activity against recombinant human angiotensin-converting enzyme (rhACE2) inhibited binding rhACE2 with Spike (RBD) protein. CLQ displayed highest potency low micromolar range, antiviral showing strong correlation inhibition rhACE2-RBD interaction. Altogether, our findings provide new mode action molecular target validates this pharmacophore promising lead series clinical potential therapeutics