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Volume 18
Issue 10
10.3390/ph18101565
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Novel Multifunctional Cannabidiol-Based Analogues with In Silico, In Vitro, and In Vivo Anti-SARS-CoV-2 Effect

by
Graziella dos Reis Rosa Franco
1,
Vanessa Silva Gontijo
1,
Flávia Pereira Dias Viegas
1,
Matheus de Freitas Silva
1,
Cindy Juliet Cristancho Ortiz
1,
Caio Miranda Damásio
1,
Isabella Marie Fernandes Silva
1,
Thâmara Gaspar Campos
1,
Erik Vinicius de Sousa Reis
2,
Felipe Alves Clarindo
2,
Thaís de Fátima Silva Moraes
2,
Matheus Müller Pereira da Silva
3,
Patrícia Ribeiro de Carvalho França
4,
Isabella Alvim Guedes
3,
Laurent Emmanuel Dardenne
3,
Jordana Grazziela Alves Coelho dos Reis
2,
Patrícia Dias Fernandes
4,* and
Claudio Viegas, Jr.
1,*
1
Laboratório de Pesquisa em Química Medicinal (PeQuiM), Instituto de Química, Universidade Federal de Alfenas, Alfenas 37130-001, Minas Gerais, Brazil
2
Laboratório de Virologia Básica e Aplicada, Instituto de Ciências Biológicas, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Minas Gerais, Brazil
3
Laboratório Nacional de Computação Científica (LNCC), Petrópolis 25651-075, Rio de Janeiro, Brazil
4
Laboratório de Farmacologia da Dor e da Inflamação, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, Brazil
*
Authors to whom correspondence should be addressed.
Pharmaceuticals 2025, 18(10), 1565; https://doi.org/10.3390/ph18101565
Submission received: 23 July 2025 / Revised: 22 September 2025 / Accepted: 11 October 2025 / Published: 16 October 2025
(This article belongs to the Special Issue Medicinal Potential of Cannabidiol and New Structural Analogs)
Versions Notes

Abstract

Background/Objectives: COVID-19 was responsible for millions of deaths worldwide. This study aimed to identify substances with in vitro and in vivo effects against the SARS-CoV-2 virus. Methods: Compounds PQM-243 and PQM-249, two terpene-N-acyl-aryl-hydrazone analogues, were evaluated in vitro against SARS-CoV-2 to a antiviral activity and inhibitory effect against angiotensin converting enzyme 2 (ACE2). A possible inhibitory effect affecting the interaction between the receptor-binding domain (RBD) protein and/or ACE2 was evaluated using LUMMIT kit. A SARS-CoV-2-induced pulmonary pneumonia model was developed to evaluate the effects of the compounds after 3 days of treatment. Results: Compounds PQM-243 and PQM-249 exhibited IC50 values of 0.0648 ± 0.041 µM and 0.2860 ± 0.057 µM against SARS-CoV-2 with a selective index of >1543.21 and 349.65, respectively, and IC50 values of 12.1 nM and 13.3 nM, respectively, against ACE2. All concentrations used significantly reduced interactions between ACE2 and RBD. Computational studies suggest that these new compounds are 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 the oral route, both compounds reduced SARS-CoV-2-induced lung inflammation. Our data suggests that both compounds can act as potent direct anti-SARS-CoV-2 agents, reducing both viral viability and host cell entry. In addition, they exhibited a significant multi-target-directed pharmacological profile, also reducing SARS-CoV-2-induced lung inflammation when administered orally. Conclusions: Overall, these findings support further investigation of PQM-243 and PQM-249 as promising antiviral and anti-inflammatory multi-target prototypes for the development of innovative drug candidates targeting SARS-CoV-2 and other virus-related respiratory diseases.
Keywords: SARS-CoV-2; COVID-19; antiviral effect; ACE2 inhibitors; multifunctional cannabidiol-based analogues SARS-CoV-2; COVID-19; antiviral effect; ACE2 inhibitors; multifunctional cannabidiol-based analogues

Share and Cite

MDPI and ACS Style

Franco, G.d.R.R.; Gontijo, V.S.; Viegas, F.P.D.; Silva, M.d.F.; Ortiz, C.J.C.; Damásio, C.M.; Silva, I.M.F.; Campos, T.G.; Reis, E.V.d.S.; Clarindo, F.A.; et al. Novel Multifunctional Cannabidiol-Based Analogues with In Silico, In Vitro, and In Vivo Anti-SARS-CoV-2 Effect. Pharmaceuticals 2025, 18, 1565. https://doi.org/10.3390/ph18101565

AMA Style

Franco GdRR, Gontijo VS, Viegas FPD, Silva MdF, Ortiz CJC, Damásio CM, Silva IMF, Campos TG, Reis EVdS, Clarindo FA, et al. Novel Multifunctional Cannabidiol-Based Analogues with In Silico, In Vitro, and In Vivo Anti-SARS-CoV-2 Effect. Pharmaceuticals. 2025; 18(10):1565. https://doi.org/10.3390/ph18101565

Chicago/Turabian Style

Franco, Graziella dos Reis Rosa, Vanessa Silva Gontijo, Flávia Pereira Dias Viegas, Matheus de Freitas Silva, Cindy Juliet Cristancho Ortiz, Caio Miranda Damásio, Isabella Marie Fernandes Silva, Thâmara Gaspar Campos, Erik Vinicius de Sousa Reis, Felipe Alves Clarindo, and et al. 2025. "Novel Multifunctional Cannabidiol-Based Analogues with In Silico, In Vitro, and In Vivo Anti-SARS-CoV-2 Effect" Pharmaceuticals 18, no. 10: 1565. https://doi.org/10.3390/ph18101565

APA Style

Franco, G. d. R. R., Gontijo, V. S., Viegas, F. P. D., Silva, M. d. F., Ortiz, C. J. C., Damásio, C. M., Silva, I. M. F., Campos, T. G., Reis, E. V. d. S., Clarindo, F. A., Moraes, T. d. F. S., Silva, M. M. P. d., França, P. R. d. C., Guedes, I. A., Dardenne, L. E., Reis, J. G. A. C. d., Fernandes, P. D., & Viegas, C., Jr. (2025). Novel Multifunctional Cannabidiol-Based Analogues with In Silico, In Vitro, and In Vivo Anti-SARS-CoV-2 Effect. Pharmaceuticals, 18(10), 1565. https://doi.org/10.3390/ph18101565

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