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A methanol extract and N,N-dimethyltryptamine from Psychotria viridis Ruiz & Pav. inhibit Zika virus infection in vitro

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Abstract

Zika virus (ZIKV) is a public health problem due to its association with serious fetal and neurological complications and the lack of antiviral agents and licensed vaccines against this virus. Surveillance studies have alerted about the potential occurrence of a new South American epidemic episode due to the recent circulation of an African ZIKV strain detected in Brazil. Therefore, it is essential to discover antiviral agents, including natural substances, that are capable of neutralizing the action of ZIKV. Several Psychotria species have antimicrobial and anti-inflammatory properties. Thus, a methanol extract and dimethyltryptamine from Psychotria viridis were evaluated for their ability to inhibit ZIKV infection in vitro by measuring the effective concentration that protects 50% of cells and investigating their possible mechanisms of action. The tested samples showed antiviral activity against ZIKV. The extract showed virucidal activity, affecting viral and non-cellular elements, inactivating the virus before infection or when it becomes extracellular after the second cycle of infection. It was also observed that both extract and dimethyltryptamine could inhibit the virus at intracellular stages of the viral cycle. In addition to dimethyltryptamine, it is believed that other compounds also contribute to the promising virucidal effect observed for the methanol extract. To our knowledge, this is the first report of the activity of a methanolic extract and dimethyltryptamine from Psychotria viridis against cellular ZIKV infection. These two samples, extracted from natural sources, are potential candidates for use as antiviral drugs to inhibit ZIKV infections.

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Abbreviations

ANOVA:

Analysis of variance

ATCC:

American Type Culture Collection

CC50 :

50% Cytotoxic concentration

CMC:

Carboxymethylcellulose

CZS:

Congenital Zika syndrome

DMSO:

Dimethyl sulfoxide

DMT:

N,N-dimethyltryptamine

EC50 :

50% Effective concentration

FBS:

Fetal bovine serum

HIV:

Human immunodeficiency virus

hpi:

Hours post-infection

min:

Minutes

moi:

Multiplicity of infection

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

RIB:

Ribavirin

SI:

Selective index

TRP:

Tryptamine

WHO:

World Health Organization

ZIKV:

Zika virus

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Acknowledgments

We thank Dr. Erna Geessien Kroon for kindly providing the Zika virus strain for this work, and the Universidade Federal de São João del-Rei for a Master's degree grant (TSFM) and the facilities to carry out this work. We thank the Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for financial suport.

Funding

This work was suported by the Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

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Authors and Affiliations

  1. Department of Chemistry, Biotechnology and Bioprocess Engineering, Universidade Federal de São João del-Rei, Rodovia MG 443, Km7, Ouro Branco, MG, 36420-000, Brazil

    Thaís F. S. Moraes, Ariane C. Ferraz, Waleska S. da Cruz Nizer, Antônio H. Tótola & José C. de Magalhães

  2. Department of Microbiology, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, Belo Horizonte, MG, 31270-901, Brazil

    Thaís F. S. Moraes

  3. Department of Biological Sciences, Universidade Federal de Ouro Preto, Campus Morro do Cruzeiro, Ouro Prêto, MG, 35400-000, Brazil

    Ariane C. Ferraz & Cintia L. B. Magalhães

  4. Department of Health Sciences, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada

    Waleska S. da Cruz Nizer

  5. Department of Chemistry, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil

    Débora B. S. Soares & Lucienir P. Duarte

  6. Department of Pharmacy, Pharmacy’s School, Universidade Federal de Ouro Preto, Campus Morro do Cruzeiro, Ouro Preto, MG, 35400-000, Brazil

    Sidney A. Vieira-Filho

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  1. Thaís F. S. Moraes
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  2. Ariane C. Ferraz
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  4. Antônio H. Tótola
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  6. Lucienir P. Duarte
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  7. Sidney A. Vieira-Filho
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  8. Cintia L. B. Magalhães
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  9. José C. de Magalhães
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Contributions

TFSM: conceptualization, methodology, software, validation, formal analysis, writing—Original draft. ACF: conceptualization, methodology, software, formal analysis, writing—original draft. WSCN: methodology, software, writing—original draft. AHT: software. DBSS: resources. LPD: resources, writing—review and editing. SAV-F: resources, writing—review and editing. CLBM: resources, writing—review and editing. JCM: conceptualization, formal analysis, investigation, resources, writing—review and editing, supervision, project administration, funding acquisition

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Correspondence to José C. de Magalhães.

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Moraes, T.F.S., Ferraz, A.C., da Cruz Nizer, W.S. et al. A methanol extract and N,N-dimethyltryptamine from Psychotria viridis Ruiz & Pav. inhibit Zika virus infection in vitro. Arch Virol 166, 3275–3287 (2021). https://doi.org/10.1007/s00705-021-05230-8

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