A natural compound from plant, Thailandiol as a potential dual inhibitor for spike glycoprotein, and RBD region of ACE2-spike glycoprotein: an insilico ADMET analysis and molecular docking study

Abstract

COVID-19 primarily targets the angiotensin-converting enzyme 2 (ACE2) receptor, which enables the virus to infiltrate host cells via the spike glycoprotein. In this research, Thailandiol could serve as a dual inhibitor for the spike glycoprotein and the interface of the spike glycoprotein and ACE2. This was achieved using molecular docking and ADMET analysis. We docked Thailandiol against the crystal structures of the spike glycoprotein and the Receptor Binding Domain region of SARS-CoV-2 and the ACE2 receptor using AutoDock4 & Vina. Thailandiol demonstrated high binding affinity and favourable interactions with both the spike glycoprotein and the RBD region. Additionally, Thailandiol exhibited favourable ADMET properties and Swiss target prediction. Our in-silico research indicates that Thailandiol has the potential to be a dual inhibitor for the spike glycoprotein and the interface of the RBD region, and could be developed into a novel therapeutic agent for COVID-19.

Graphical Abstract

Acknowledgements

We would like to express our sincere gratitude to Govindaraju SHRUTHI for their valuable guidance and support throughout this research project. Additionally, we would like to acknowledge the contributions of Govindaraju SHRUTHI for their insightful discussions and feedback.

Lastly, we would like to express our deep appreciation to our families and friends for their unwavering support and encouragement throughout this endeavor.

Author’s contribution and information

N Sushmitha conceived of the presented idea, developed the theory, and performed ADME analysis, Molecular docking, SWISS TARGET Analysis and contributed to the final Manuscript. Independent researcher [email protected], Phone no.+919066999699.

Data and software availability

Structures of natural compound downloaded from PubChem database. https://pubchem.ncbi.nlm.nih.gov/.

Structures of protein were downloaded from Protein data bank, accession numbers 7WPB and 7TGW. Also, for binding site prediction http://sts.bioe.uic.edu/castp/index.html?1bxw.

Target analysis downloaded from SWISS TARGET database http://www.swisstargetprediction.ch/.and ADME analysis from SWISS ADME http://www.swissadme.ch/.

All molecular modelling analyses were done using AutoDock4.https://autodock.scripps.edu/ and AutoDock Vina (Trott and Olson 2010) and visualised in BIOVIA, Dassault Systèmes, [Discovery Studio Visualizer], [v21.1.0.20298], San Diego: Dassault Systèmes, [2020]

We performed multiple sequence alignment analysis using Clustal Omega, Wang, Jiyao et al. “The conserved domain database in 2023.” Nucleic acids research vol. 51, D1 (2023): D384-D388. doi:10.1093/nar/gkac1096 and the structural information of the protein was obtained from UniProt. The UniProt Consortium, UniProt: the Universal Protein Knowledgebase in 2023, Nucleic Acids Research, Volume 51, Issue D1, 6 January 2023, Pages D523–D531, https://doi.org/10.1093/nar/gkac1052.

The extended data that support the findings of this study are available on request from the author.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.