Computational and experimental insights on the interaction of artemisinin, dihydroartemisinin and chloroquine with SARS-CoV-2 spike protein receptor-binding domain (RBD). Issue 20 (13th October 2022)

• Record Type: Journal Article
• Authors: Ribaudo, Giovanni; Coghi, Paolo; Yang, Li Jun; Ng, Jerome P. L.; Mastinu, Andrea; Memo, Maurizio; Wong, Vincent Kam Wai; Gianoncelli, Alessandra
• Is Part Of: Natural product research. Volume 36:Issue 20(2022)
• Page Start: 5358
• Page End: 5363
• Publication Date: 2022-10-13
• Subjects: SARS-CoV-2 -- artemisinin -- spike protein -- molecular dynamics -- bio-layer interferometry; Natural products -- Periodicals; Natural products -- Research -- Periodicals; Biological Factors -- Periodicals; Biological Products -- Periodicals; 547
• DOI: 10.1080/14786419.2021.1925894
• Languages: English
• ISSNs: 1478-6419

Abstract

Abstract: The mechanism of host cell invasion of severe acute respiratory syndrome coronavirus-2 SARS-CoV-2 is connected with the interaction of spike protein (S) with angiotensin-converting enzyme 2 (ACE2) through receptor-binding domain (RBD). Small molecules targeting this assembly are being investigated as drug candidates to contrast SARS-CoV-2. In this context, chloroquine, an antimalarial agent proposed as a repurposed drug to treat coronavirus disease-19 (COVID-19), was hypothesized to bind RBD among its other mechanisms. Similarly, artemisinin and its derivatives are being studied as potential antiviral agents. In this work, we investigated the interaction of artemisinin, its metabolite dihydroartemisinin and chloroquine with RBD by means of computational tools and in vitro . Docking studies showed that the compounds interfere with the same region of the protein and molecular dynamics (MD) simulations demonstrated the stability of the predicted complexes. Bio-layer interferometry showed that chloroquine dose-dependently binds RBD (KD = 35.9 µM) more efficiently than artemisinins.