Predicting the Anti-SARS-CoV-2 Potential of Isoquinoline Alkaloids from Brazilian Siparunaceae Species Using Chemometric Tools

Gomes, Brendo Araujo; Fernandes, Diégina Araújo; Mendonça, Simony Carvalho; Campos, Mariana Freire; da Fonseca, Thamirys Silva; Constant, Larissa Esteves Carvalho; de Sousa, Natalia Ferreira; Priscila Barros de Menezes, Renata; de Oliveira, Beatriz Albuquerque Custódio; da Silva Costa, Stephany; Frensel, Giovanna Barbosa; Rosa, Alice Santos; Oliveira, Thamara Kelcya Fonseca; Tucci, Amanda Resende; Lima, Júlia Nilo Henrique; Ferreira, Vivian Neuza Santos; Miranda, Milene Dias; Allonso, Diego; Scotti, Marcus Tullius; Leitão, Suzana Guimarães; Leitão, Gilda Guimarães

doi:10.3390/ijms26020633

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Open AccessArticle

Predicting the Anti-SARS-CoV-2 Potential of Isoquinoline Alkaloids from Brazilian Siparunaceae Species Using Chemometric Tools

by

Brendo Araujo Gomes

^1,2,†

,

Diégina Araújo Fernandes

^3,†

,

Simony Carvalho Mendonça

^2,4

,

Mariana Freire Campos

^1,2

,

Thamirys Silva da Fonseca

^2,4

,

Larissa Esteves Carvalho Constant

⁵,

Natalia Ferreira de Sousa

⁶,

Renata Priscila Barros de Menezes

⁶

,

Beatriz Albuquerque Custódio de Oliveira

⁷,

Stephany da Silva Costa

⁷,

Giovanna Barbosa Frensel

⁷

,

Alice Santos Rosa

^8,9

,

Thamara Kelcya Fonseca Oliveira

^8,9,

Amanda Resende Tucci

^8,9

,

Júlia Nilo Henrique Lima

⁸

,

Vivian Neuza Santos Ferreira

⁸,

Milene Dias Miranda

^8,9,

Diego Allonso

^5,7,10

,

Marcus Tullius Scotti

^6,10

,

Suzana Guimarães Leitão

^1,2,4,*

and

Gilda Guimarães Leitão

^3,4,*

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¹

Programa de Pós-Graduação em Biotecnologia Vegetal e Bioprocessos, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil

²

Departamento de Produtos Naturais e Alimentos, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil

³

Instituto de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil

⁴

Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil

⁵

Programa de Pós-Graduação em Ciências Biológicas, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, RJ, Brazil

⁶

Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos, Universidade Federal da Paraíba, João Pessoa 58015-970, PB, Brazil

⁷

Laboratório de Biotecnologia e Bioengenharia Estrutural, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Bloco G, Rio de Janeiro 21941-902, RJ, Brazil

⁸

Laboratório de Morfologia e Morfogênese Viral, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21041-250, RJ, Brazil

⁹

Programa de Pós-Graduação em Biologia Celular e Molecular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21041-250, RJ, Brazil

¹⁰

Departamento de Biotecnologia Farmacêutica, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2025, 26(2), 633; https://doi.org/10.3390/ijms26020633

Submission received: 1 December 2024 / Revised: 23 December 2024 / Accepted: 3 January 2025 / Published: 13 January 2025

(This article belongs to the Collection Bioactive Natural Compounds for Therapeutics and Nutraceutical Applications)

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Abstract

The COVID-19 pandemic has caused over 7 million deaths globally in the past four years. Siparuna spp. (Siparunaceae), which is used in Brazilian folk medicine, is considered a genus with potential antiviral alternatives. This study explored the correlation between phytochemicals in Siparuna leaf extracts (S. ficoides, S. decipiens, S. glycycarpa, S. reginae, and S. cymosa) and their potential against various SARS-CoV-2 targets. In vitro assays examined interactions between the spike protein and the ACE2 receptor, protease activity, and viral replication inhibition in Calu-3 cell models. UHPLC-MS/MS analysis, processed with MZmine and evaluated chemometrically, revealed isoquinoline alkaloids with bulbocapnine, showing promising therapeutic potential. Predictions regarding absorption, distribution, metabolism, excretion, and toxicity were conducted, along with molecular docking and dynamics simulations, to evaluate protein−ligand interaction stability. The results confirmed the antiviral activity of the Siparuna genus against SARS-CoV-2 targets, with 92% of the extracts maintaining over 70% cellular viability at 200 μg·mL⁻¹ and 80% achieving more than 50% viral activity suppression at 50 μg·mL⁻¹. These findings highlight the potential of isoquinoline alkaloids as novel anti-coronavirus agents and support the need for further exploration, isolation, and testing of Siparuna compounds in the fight against COVID-19.

Keywords: Brazilian folk medicine; Siparuna spp.; SARS-CoV-2; UHPLC-MS/MS; chemometric analyses; molecular docking; dynamics simulations; ADMET predictions; bulbocapnine

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MDPI and ACS Style

Gomes, B.A.; Fernandes, D.A.; Mendonça, S.C.; Campos, M.F.; da Fonseca, T.S.; Constant, L.E.C.; de Sousa, N.F.; Priscila Barros de Menezes, R.; de Oliveira, B.A.C.; da Silva Costa, S.; et al. Predicting the Anti-SARS-CoV-2 Potential of Isoquinoline Alkaloids from Brazilian Siparunaceae Species Using Chemometric Tools. Int. J. Mol. Sci. 2025, 26, 633. https://doi.org/10.3390/ijms26020633

AMA Style

Gomes BA, Fernandes DA, Mendonça SC, Campos MF, da Fonseca TS, Constant LEC, de Sousa NF, Priscila Barros de Menezes R, de Oliveira BAC, da Silva Costa S, et al. Predicting the Anti-SARS-CoV-2 Potential of Isoquinoline Alkaloids from Brazilian Siparunaceae Species Using Chemometric Tools. International Journal of Molecular Sciences. 2025; 26(2):633. https://doi.org/10.3390/ijms26020633

Chicago/Turabian Style

Gomes, Brendo Araujo, Diégina Araújo Fernandes, Simony Carvalho Mendonça, Mariana Freire Campos, Thamirys Silva da Fonseca, Larissa Esteves Carvalho Constant, Natalia Ferreira de Sousa, Renata Priscila Barros de Menezes, Beatriz Albuquerque Custódio de Oliveira, Stephany da Silva Costa, and et al. 2025. "Predicting the Anti-SARS-CoV-2 Potential of Isoquinoline Alkaloids from Brazilian Siparunaceae Species Using Chemometric Tools" International Journal of Molecular Sciences 26, no. 2: 633. https://doi.org/10.3390/ijms26020633

APA Style

Gomes, B. A., Fernandes, D. A., Mendonça, S. C., Campos, M. F., da Fonseca, T. S., Constant, L. E. C., de Sousa, N. F., Priscila Barros de Menezes, R., de Oliveira, B. A. C., da Silva Costa, S., Frensel, G. B., Rosa, A. S., Oliveira, T. K. F., Tucci, A. R., Lima, J. N. H., Ferreira, V. N. S., Miranda, M. D., Allonso, D., Scotti, M. T., ... Leitão, G. G. (2025). Predicting the Anti-SARS-CoV-2 Potential of Isoquinoline Alkaloids from Brazilian Siparunaceae Species Using Chemometric Tools. International Journal of Molecular Sciences, 26(2), 633. https://doi.org/10.3390/ijms26020633

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Predicting the Anti-SARS-CoV-2 Potential of Isoquinoline Alkaloids from Brazilian Siparunaceae Species Using Chemometric Tools

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