An Androsterone-H2 @C60 hybrid: Synthesis, Properties and Molecular Docking Simulations with SARS-Cov-2

Chempluschem. 2021 Jul;86(7):972-981. doi: 10.1002/cplu.202000770. Epub 2021 Feb 4.

Abstract

We report the synthesis and characterization of a fullerene-steroid hybrid that contains H2 @C60 and a dehydroepiandrosterone moiety synthesized by a cyclopropanation reaction with 76 % yield. Theoretical calculations at the DFT-D3(BJ)/PBE 6-311G(d,p) level predict the most stable conformation and that the saturation of a double bond is the main factor causing the upfield shielding of the signal appearing at -3.13 ppm, which corresponds to the H2 located inside the fullerene cage. Relevant stereoelectronic parameters were also investigated and reinforce the idea that electronic interactions must be considered to develop studies on chemical-biological interactions. A molecular docking simulation predicted that the binding energy values for the protease-hybrid complexes were -9.9 kcal/mol and -13.5 kcal/mol for PLpro and 3CLpro respectively, indicating the potential use of the synthesized steroid-H2 @C60 as anti-SARS-Cov-2 agent.

Keywords: SARS-Cov-2; cyclopropanation; fullerenes; molecular docking; steroid hybrids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androsterone / chemistry*
  • Antiviral Agents / chemistry*
  • Antiviral Agents / metabolism
  • Binding Sites
  • COVID-19 / pathology
  • COVID-19 / virology
  • Coronavirus 3C Proteases / chemistry
  • Coronavirus 3C Proteases / metabolism
  • Coronavirus Papain-Like Proteases / chemistry
  • Coronavirus Papain-Like Proteases / metabolism
  • Density Functional Theory
  • Fullerenes / chemistry*
  • Humans
  • Molecular Docking Simulation*
  • Protein Binding
  • SARS-CoV-2 / isolation & purification
  • SARS-CoV-2 / metabolism*
  • Static Electricity
  • Thermodynamics

Substances

  • Antiviral Agents
  • Fullerenes
  • Androsterone
  • 3C-like protease, SARS coronavirus
  • Coronavirus Papain-Like Proteases
  • papain-like protease, SARS-CoV-2
  • Coronavirus 3C Proteases
  • fullerene C60