Synthesis and in silico study of chenodeoxycholic acid and its analogues as an alternative inhibitor of spike glycoprotein of SARS-CoV-2

Abstract

COVID-19, caused by SARS-CoV-2, is a viral infection that has generated one of the most significant health problems in the world. Spike glycoprotein is a crucial enzyme in viral replication and transcription mediation. There are reports in the literature on using bile acid in the fight against this virus through in vitro tests. This work presents the synthesis of nine chenodeoxycholic acid derivatives (1-9), which were prepared by oxidation, acetylation, formylation, and esterification reactions, and the analogs 6-9 have not yet been reported in the literature and the possibility of conducting an in silico study of bile acid derivatives as a therapeutic alternative to combat the virus using glycoprotein as a macromolecular target. As a result, five compounds (1, 6-9) possessed favorable competitive interactions with the lowest energies compared to the native ligand (BLA), and the highlighted compound 9 got the best scores. At the same time, analog 1 presented the best ADME filter result. Molecular dynamics also simulated these compounds to verify their stability within the active protein site to seek new therapeutic propositions to fight against the pandemic. Physical and spectroscopic data have fully characterized all the compounds.

Communicated by Ramaswamy H. Sarma

Keywords:

• Chenodeoxycholic acid
• molecular docking
• molecular dynamics
• SARS-CoV-2

Author contributions

G. R. A. was responsible for conceptualization, data curation, formal analysis, investigation, methodology, validation, visualization and writing—original draft; T. L. G. L. was responsible for project administration, conceptualization, funding acquisition, resources, supervision and writing—review & editing; R. B. F. for the formal analysis; A. M. F. for the formal analysis, methodology, software, validation, writing—original draft and review & editing; E. S. M. for the writing—original draft; P. R. V. and K. M. C. for the formal analysis and validation; F. J. Q. M. was responsible for project administration, supervision, visualization and writing—original draft and review & editing.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors would like to thank the Brazilian Agencies: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for fellowships and financial supports.