Worldwide, there are plants known as psychoactive plants that naturally contain psychedelic active components. They have a high concentration of neuroprotective substances that can interact with the nervous system to produce psychedelic effects. Despite these plants' hazardous potential, recreational use of them is on the rise because of their psychoactive properties. Early neuroscience studies relied heavily on psychoactive plants and plant natural products (NPs), and both recreational and hazardous NPs have contributed significantly to the understanding of almost all neurotransmitter systems. Worldwide, there are many plants that contain psychoactive properties, and people have been using them for ages. Psychoactive plant compounds may significantly alter how people perceive the world.
1. J Mol Graph Model. 2024 Sep;131:108803. doi: 10.1016/j.jmgm.2024.108803. Epub 2024 May 26. Utilization of the EpiMed Coronabank Chemical Collection to identify potential SARS-CoV-2 antivirals: in silico studies targeting the nsp14 ExoN domain and PL(pro) naphthalene binding site. Liang JJ(1), Pitsillou E(2), Lau HLY(3), Mccubbery CP(3), Gan H(3), Hung A(4), Karagiannis TC(5). Author information: (1)Epigenomic Medicine Laboratory at prospED Polytechnic, Carlton, VIC, 3053, Australia; School of Science, STEM College, RMIT University, Melbourne, VIC, 3001, Australia; Epigenetics in Human Health and Disease Program, Baker Heart and Diabetes Institute, 75 Commercial Road, Prahran, VIC, 3004, Australia. (2)Epigenomic Medicine Laboratory at prospED Polytechnic, Carlton, VIC, 3053, Australia; School of Science, STEM College, RMIT University, Melbourne, VIC, 3001, Australia. (3)Epigenomic Medicine Laboratory at prospED Polytechnic, Carlton, VIC, 3053, Australia; Department of Microbiology and Immunology, The University of Melbourne, Parkville, VIC, 3010, Australia. (4)School of Science, STEM College, RMIT University, Melbourne, VIC, 3001, Australia. (5)Epigenomic Medicine Laboratory at prospED Polytechnic, Carlton, VIC, 3053, Australia; Epigenetics in Human Health and Disease Program, Baker Heart and Diabetes Institute, 75 Commercial Road, Prahran, VIC, 3004, Australia; Department of Microbiology and Immunology, The University of Melbourne, Parkville, VIC, 3010, Australia; Department of Clinical Pathology, The University of Melbourne, Parkville, VIC, 3010, Australia. Electronic address: karat@unimelb.edu.au. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome encodes 29 proteins including four structural, 16 nonstructural (nsps), and nine accessory proteins (https://epimedlab.org/sars-cov-2-proteome/). Many of these proteins contain potential targetable sites for the development of antivirals. Despite the widespread use of vaccinations, the emergence of variants necessitates the investigation of new therapeutics and antivirals. Here, the EpiMed Coronabank Chemical Collection (https://epimedlab.org/crl/) was utilized to investigate potential antivirals against the nsp14 exoribonuclease (ExoN) domain. Molecular docking was performed to evaluate the binding characteristics of our chemical library against the nsp14 ExoN site. Based on the initial screen, trisjuglone, ararobinol, corilagin, and naphthofluorescein were identified as potential lead compounds. Molecular dynamics (MD) simulations were subsequently performed, with the results highlighting the stability of the lead compounds in the nsp14 ExoN site. Protein-RNA docking revealed the potential for the lead compounds to disrupt the interaction with RNA when bound to the ExoN site. Moreover, hypericin, cyanidin-3-O-glucoside, and rutin were previously identified as lead compounds targeting the papain-like protease (PLpro) naphthalene binding site. Through performing MD simulations, the stability and interactions of lead compounds with PLpro were further examined. Overall, given the critical role of the exonuclease activity of nsp14 in ensuring viral fidelity and the multifunctional role of PLpro in viral pathobiology and replication, these nsps represent important targets for antiviral drug development. Our databases can be utilized for in silico studies, such as the ones performed here, and this approach can be applied to other potentially druggable SARS-CoV-2 protein targets. Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.jmgm.2024.108803 PMID: 38815531 [Indexed for MEDLINE] Conflict of interest statement: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.