–  M. SEHAILIA ,S. CHEMAT 

Research Centre in Physical and Chemical Analysis (C.R.A.P.C), Tipaza, Algeria 

Received 21 Apr 2020, Accepted 06 Jul 2020, Published online: 22 Jul 2020
JournalJournal of Biomolecular Structure and Dynamics

Abstract

Medicinal herbs have proved along history to be a source of multiple cures. In this paper, we demonstrate how hydroxychloroquine can act as a good inhibitor of SARS-CoV-2 Spike protein receptor-binding-domain using molecular docking studies. We also unveil how hydroxychloroquine can interfere in the prevention of Lys353 in hACE2 from interacting with the corresponding binding hotspot present on the Spike protein. Further screening of artemisinin & derived compounds produced better Vina docking score than hydroxychloroquine (-7.1 kcal mol−1 for artelinic acid vs. −5.5 kcal mol−1 for hydroxychloroquine). Artesunate, artemisinin and artenimol, showed two mode of interactions with Lys353 and Lys31 binding hotspots of the Spike protein. Molecular dynamics analysis confirmed that the formed complexes are able to interact and remain stable in the active site of their respective targets. Given that these molecules are effective antivirals with excellent safety track records in humans against various ailment, we recommend their potential repurposing for the treatment of SARS-CoV-2 patients after successful clinical studies. In addition, an extraction protocol for artemisinin from Artemisia annua L. is proposed in order to cope with the potential urgent global demand.

  • Highlights
  • Hydroxychloroquine role to prevent hACE2 from interacting with SARS-CoV-2 Spike protein is unveiled
  • Artemisinin & derivatives entangle Lys353 & Lys31 binding hotspots of virus Spike protein and prevent infection
  • Artemisinin, artesunate and artenimol stand as strong repurposing cadidates for COVID-19 clinical trials

Keywords: SARS-CoV-2COVID-19spike proteinhACE2antiviralhydroxychloroquineartemisinin

https://www.tandfonline.com/doi/full/10.1080/07391102.2020.1796809