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Research Articles

Withanolides of Athenaea velutina with potential inhibitory properties against SARS coronavirus main protease (mpro): molecular modeling studies

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Pages 12267-12275 | Received 11 Aug 2022, Accepted 01 Jan 2023, Published online: 23 Jan 2023
 

Abstract

Since the global COVID-19 pandemic began, the scientific community has dedicated efforts to finding effective antiviral drugs to treat or minimize the effects caused by the SARS-CoV-2 coronavirus. Some targets can act as inhibitor substrates, highlighting the Main Protease (Mpro), which plays an essential role in the translation and transcription of the virus cycle. Withanolides, a class of natural C28 steroidal lactones, are compounds of interest as possible inhibitors of Mpro and other critical targets of the virus, such as papain-like protease. In this study, the isolation of a new withanolide (1), along with the known 27-deoxywithaferin A (2) and 27-deoxy-2,3-dihydrowithaferin A (3), from the leaves of Athenaea velutina (Solanaceae) is described. Their structures were determined using spectroscopic and spectrometric methods (NMR, IR, HRESIMS). Moreover, the interaction and the stability of withanolides 13 and withanolide D (4), previously isolated of Acnistus arborescens, against the Mpro target through molecular docking, molecular dynamics, and binding free energy simulations were analyzed. The molecular dynamics results indicated that the complexes formed by the molecular docking simulations between the Mpro target with each of the withanolides 14 exhibited good stability during the simulations due to a slight change in the structure of complexes. The binding free energy results suggested that withanolide (1) can be a natural candidate against COVID-19 disease.

Communicated by Ramaswamy H. Sarma

Acknowledgments

The authors thank High-Performance Computing Center (NPAD) at the Federal University of Rio Grande do Norte (UFRN) and the National High-Performance Processing Center of the Federal University of Ceará (UFC) for providing computational resources.

Disclosure statement

The authors declare no competing or financial interest.

Ethical statement

This study does not require ethics approval.

Additional information

Funding

This work was supported by the Instituto Nacional de Ciência e Tecnologia - INCT BioNat under Grant N°. 465637/2014-0; Conselho Nacional de Desenvolvimento Científico e TecnológicoCNPq under Grant N°. 420454/2016-0, N°. 10183/2020-0, and N°. 140562/2019-2.

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