Computational and experimental insights on the interaction of artemisinin, dihydroartemisinin and chloroquine with SARS-CoV-2 spike protein receptor-binding domain (RBD)

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.

Keywords:

• SARS-CoV-2
• artemisinin
• spike protein
• molecular dynamics
• bio-layer interferometry

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This work was granted from the University of Brescia and Macau University of Science and Technology, thanks to FDCT grant from the Macao Science and Technology Development Fund (Project code: 0096/2020/A).