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Anti-COVID-19 Potential of Withaferin-A and Caffeic Acid Phenethyl Ester.
- Source :
-
Current topics in medicinal chemistry [Curr Top Med Chem] 2024; Vol. 24 (9), pp. 830-842. - Publication Year :
- 2024
-
Abstract
- Background: The recent COVID-19 (coronavirus disease 2019) pandemic triggered research on the development of new vaccines/drugs, repurposing of clinically approved drugs, and assessment of natural anti-COVID-19 compounds. Based on the gender difference in the severity of the disease, such as a higher number of men hospitalized and in intense care units, variations in sex hormones have been predicted to play a role in disease susceptibility. Cell surface receptors (Angiotensin-Converting Enzyme 2; ACE2 and a connected transmembrane protease serine 2- TMPSS2) are upregulated by androgens. Conversely, androgen antagonists have also been shown to lower ACE2 levels, implying their usefulness in COVID-19 management.<br />Objectives: In this study, we performed computational and cell-based assays to investigate the anti- COVID-19 potential of Withaferin-A and Caffeic acid phenethyl ester, natural compounds from Withania somnifera and honeybee propolis, respectively.<br />Methods: Structure-based computational approach was adopted to predict binding stability, interactions, and dynamics of the two test compounds to three target proteins (androgen receptor, ACE2, and TMPRSS2). Further, in vitro , cell-based experimental approaches were used to investigate the effect of compounds on target protein expression and SARS-CoV-2 replication.<br />Results: Computation and experimental analyses revealed that (i) CAPE, but not Wi-A, can act as androgen antagonist and hence inhibit the transcriptional activation function of androgen receptor, (ii) while both Wi-A and CAPE could interact with ACE2 and TMPRSS2, Wi-A showed higher binding affinity, and (iii) combination of Wi-A and CAPE (Wi-ACAPE) caused strong downregulation of ACE2 and TMPRSS2 expression and inhibition of virus infection.<br />Conclusion: Wi-A and CAPE possess multimodal anti-COVID-19 potential, and their combination (Wi-ACAPE) is expected to provide better activity and hence warrant further attention in the laboratory and clinic.<br /> (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Subjects :
- Humans
Molecular Docking Simulation
Antiviral Agents pharmacology
Antiviral Agents chemistry
Receptors, Androgen metabolism
COVID-19 virology
COVID-19 metabolism
Animals
Chlorocebus aethiops
Angiotensin-Converting Enzyme 2 metabolism
Phenylethyl Alcohol analogs & derivatives
Phenylethyl Alcohol pharmacology
Phenylethyl Alcohol chemistry
COVID-19 Drug Treatment
Caffeic Acids pharmacology
Caffeic Acids chemistry
Withanolides pharmacology
Withanolides chemistry
Serine Endopeptidases metabolism
SARS-CoV-2 drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4294
- Volume :
- 24
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Current topics in medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 38279743
- Full Text :
- https://doi.org/10.2174/0115680266280720231221100004