Discovery of potential small molecular SARS-CoV-2 entry blockers targeting the spike protein

Acta Pharmacol Sin. 2022 Apr;43(4):788-796. doi: 10.1038/s41401-021-00735-z. Epub 2021 Aug 4.

Abstract

An epidemic of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. SARS-CoV-2 relies on its spike protein to invade host cells by interacting with the human receptor protein Angiotensin-Converting Enzymes 2 (ACE2). Therefore, designing an antibody or small-molecular entry blockers is of great significance for virus prevention and treatment. This study identified five potential small molecular anti-virus blockers via targeting SARS-CoV-2 spike protein by combining in silico technologies with in vitro experimental methods. The five molecules were natural products that binding to the RBD domain of SARS-CoV-2 was qualitatively and quantitively validated by both native Mass Spectrometry (MS) and Surface Plasmon Resonance (SPR). Anti-viral activity assays showed that the optimal molecule, H69C2, had a strong binding affinity (dissociation constant KD) of 0.0947 µM and anti-virus IC50 of 85.75 µM.

Keywords: SARS-CoV-2; natural products; protein-protein interaction modulators; spike protein; virtual screening.

MeSH terms

  • COVID-19* / drug therapy
  • Humans
  • Protein Binding
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus*

Substances

  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2