Novel multifunctional Cannabidiol-Based Analogues with In Silico, In Vitro, and In vivo anti-SARS-COV-2 effect

Novel multifunctional Cannabidiol-Based Analogues with In Silico, In Vitro, and In vivo anti-SARS-COV-2 effect | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 14 May 2025 V1 Latest version Share on Novel multifunctional Cannabidiol-Based Analogues with In Silico, In Vitro, and In vivo anti-SARS-COV-2 effect Authors : Graziela Franco , Vanessa Gontijo , Flávia Viegas , Matheus Silva , Cindy Ortiz , Caio Damásio , Isabela Silva , … Show All … , Thâmara Campos , Erik Reis , Felipe Clarindo , Thais Moraes , Matheus Silva , Patricia França , Isabella Guedes , Laurent Dardenne , Jordana Reis , Patricia Fernandes 0000-0001-6870-6745 [email protected] , and Claudio Viegas Jr Show Fewer Authors Info & Affiliations https://doi.org/10.22541/au.174724783.36294812/v1 Published Pharmaceuticals Version of record Peer review timeline 391 views 112 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background and Purpose: COVID-19 was responsible for millions of deaths worldwide. This study aimed to identify substances with in vitro and in vivo effect agains the virus. Experimental Approach: compounds PQM-243 and PQM-249, two terpene-N-acyl-aryl-hydrazone analogues were evaluated in vitro against SARS-CoV-2 to evaluate an antiviral activity and an inhibitory activity against angiotensin converting enzyme 2 (ACE2). A possible inhibitory effect inhibiting the interaction between RBD protein and/or ACE2 was evaluates using LUMMIT kit. A SARS-CoV-2-induced pulmonary pneumonia model was developed to evaluate the effects of compounds after 3 days of treatment. Key Results: PQM-243 and PQM-249 exhibited IC50 0.005 and 0.170 µM against the virus with selective index of >20,000 and 588.23 and IC50 against ACE2 was 12.1 and 13.3, respectively. All concentrations used significantly reduced interactions between ACE2 and RBD. Computational data suggest these new compounds as potent direct anti-SARS-CoV-2 agents, capable of reducing both virus viability and its invasive ability in the host cells by reducing the interaction between RBD and ACE2. It was also demonstrated that even when administered by oral route, both compounds reduced SARS-CoV-2-induced lung inflammation. Conclusion and Implications: our data suggest that compounds can act as potent direct anti-SARS-CoV-2 agents reducing both viral viability and host cell entry. Both compounds exhibited a significant multi-target-directed pharmacological profile, also reducing SARS-CoV-2-induced lung inflammation when administered orally. These findings support further investigation of PQM-243 and PQM-249 as promising prototypes for the development of innovative drug candidates targeting SARS-CoV-2 and other virus-related respiratory diseases. Supplementary Material File (fernandes et al.docx) Download 784.05 KB File (tablesi1_results-docking.xlsx) Download 11.10 KB Information & Authors Information Version history V1 Version 1 14 May 2025 Peer review timeline Published Pharmaceuticals Version of Record 16 Oct 2025 Published Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords cannabinoid covid-19 respiratory pharmacology virus Authors Affiliations Graziela Franco Universidade Federal de Alfenas View all articles by this author Vanessa Gontijo Universidade Federal de Alfenas View all articles by this author Flávia Viegas Universidade Federal de Alfenas View all articles by this author Matheus Silva Universidade Federal de Alfenas View all articles by this author Cindy Ortiz Universidade Federal de Alfenas View all articles by this author Caio Damásio Universidade Federal de Alfenas View all articles by this author Isabela Silva Universidade Federal de Alfenas View all articles by this author Thâmara Campos Universidade Federal de Alfenas View all articles by this author Erik Reis Universidade Federal de Minas Gerais View all articles by this author Felipe Clarindo Universidade Federal de Minas Gerais View all articles by this author Thais Moraes Universidade Federal de Minas Gerais View all articles by this author Matheus Silva Laboratório Nacional de Computação Científica View all articles by this author Patricia França Universidade Federal do Rio de Janeiro View all articles by this author Isabella Guedes Laboratorio Nacional de Computacao Cientifica View all articles by this author Laurent Dardenne Laboratório Nacional de Computação Científica View all articles by this author Jordana Reis Universidade Federal de Minas Gerais View all articles by this author Patricia Fernandes 0000-0001-6870-6745 [email protected] Federal University of Rio de Janeiro View all articles by this author Claudio Viegas Jr Universidade Federal de Alfenas View all articles by this author Metrics & Citations Metrics Article Usage 391 views 112 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Graziela Franco, Vanessa Gontijo, Flávia Viegas, et al. Novel multifunctional Cannabidiol-Based Analogues with In Silico, In Vitro, and In vivo anti-SARS-COV-2 effect. Authorea . 14 May 2025. DOI: https://doi.org/10.22541/au.174724783.36294812/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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