Theobroma cacao L. compounds: Theoretical study and molecular modeling as inhibitors of main SARS-CoV-2 protease

Osvaldo Yañez, Manuel Isaías Osorio, Carlos Areche, Alejandro Vasquez-Espinal, Jessica Bravo, Angélica Sandoval-Aldana, José M. Pérez-Donoso, Fernando González-Nilo, Maria João Matos, Edison Osorio, Olimpo García-Beltrán, William Tiznado

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


Cocoa beans contain antioxidant molecules with the potential to inhibit type 2 coronavirus (SARS-CoV-2), which causes a severe acute respiratory syndrome (COVID-19). In particular, protease. Therefore, using in silico tests, 30 molecules obtained from cocoa were evaluated. Using molecular docking and quantum mechanics calculations, the chemical properties and binding efficiency of each ligand was evaluated, which allowed the selection of 5 compounds of this series. The ability of amentoflavone, isorhoifolin, nicotiflorin, naringin and rutin to bind to the main viral protease was studied by means of free energy calculations and structural analysis performed from molecular dynamics simulations of the enzyme/inhibitor complex. Isorhoifolin and rutin stand out, presenting a more negative binding ΔG than the reference inhibitor N-[(5-methylisoxazol-3-yl)carbonyl]alanyl-L-valyl-N~1~-((1R,2Z)−4-(benzyloxy)−4-oxo-1-{[(3R)−2-oxopyrrolidin-3-yl]methyl}but-2-enyl)-L-leucinamide (N3). These results are consistent with high affinities of these molecules for the major SARS-CoV-2. The results presented in this paper are a solid starting point for future in vitro and in vivo experiments aiming to validate these molecules and /or test similar substances as inhibitors of SARS-CoV-2 protease.

Original languageEnglish
Article number111764
JournalBiomedicine and Pharmacotherapy
Publication statusPublished - Aug 2021


  • Antioxidant
  • Bioflavonoids
  • DFT
  • Molecular dynamics
  • SARS-CoV-2
  • Theobroma cacao

ASJC Scopus subject areas

  • Pharmacology


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