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RNA-dependent RNA polymerase (RdRp) natural antiviral inhibitors: a review

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Abstract

Viral diseases are the cause of many global epidemics, leading to deaths, affecting the quality of life of populations, and impairing public health. The limitations in the treatment of viral diseases and the constant resistance to conventional antiviral treatments encourage researchers to discover new compounds. In this perspective, this literature review presents isolated molecules and extracts of natural products capable of inhibiting the activity of the nonstructural protein that acts as the RNA-dependent RNA polymerase. The literature review presented natural compounds with the potential to be tested as alternative medicines or used in the development of synthetic drugs to prevent the replication of RNA viruses, such as COVID-19, hepatitis C, and dengue viruses, among others. Natural products are known to exhibit remarkable activities in mitigation of different viral diseases, in addition, they help to decrease the aggravation of infections. Consequently, reducing hospitalization time and deaths.

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Notes

  1. In fact, the inhibition of replication and transcription processes is a mechanism of action common to molecules capable of interfering with the activity of RdRp, present in RNA viruses. Flavonoids such as kaempterol, fisetin, hyperoside, afzelin, biorobin, myricitrin, astragalin, quercetin, quercetin-3-O-glycoside and quercitrin showed high affinity for RdRp using molecular docking.

Abbreviations

COVID-19 :

Coronavirus disease 2019

DAA :

Direct-acting antiviral

DENV :

Dengue

HCV :

Hepatitis C virus

HIV-1 :

Human immunodeficiency 1

MERS-CoV :

Middle East Respiratory Syndrome

NSPs :

Nonstructural proteins

PEG-IFN :

Pegylated interferon

RdRp :

RNA-dependent RNA polymerase

RdRp-DENV :

dengue virus RNA-dependent RNA polymerase

RdRp-HCV :

hepatitis C virus RNA-dependent RNA polymerase

SARS-CoV :

Severe Acute Respiratory Syndrome

WNV :

West Nile virus

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Acknowledgements

This study was supported by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior, Brazil)—Funding code 001 and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil). The authors would like to thank the Academic Publishing Advisory Center (Centro de Assessoria de Publicação Acadêmica, CAPA—www.capa.ufpr.br) of the Federal University of Paraná (UFPR) for assistance with English language translation and developmental editing. Thanks to Center National de la recherché Scientifique (CNRS-France) and to the University of Poitiers-France for support.

Author contributions

DRBL: Conceptualization, methodology, research, writing-original draft, writing-revision and editing, visualization, project administration, acquisition of financing. SPC: Research, original draft writing, acquisition of funding. KMM: Software, resources, data curation, acquisition of funding. FCMB: Formal analysis, acquisition of financing. EdBS: Formal analysis, acquisition of financing. FBM: Software, visualization, acquisition of financing. DPM: Conceptualization, acquisition of financing. JdFGD: Conceptualization, acquisition of financing. OGM: Conceptualization, acquisition of financing. MDM: Conceptualization, supervision, acquisition of financing.

Funding

DRBL, SPC, FBM, FCMB, and EdBS received funding from CAPES (Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior, Brazil), KMM received funding from Center National de la recherche Scientifique (CNRS-France), DPM and JdFGD received funding from Universidade Federal do Paraná (UFPR), CAPES (Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior, Brazil) and OGM and MDM received funding from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Universidade Federal do Paraná (UFPR).

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  1. Department of Pharmacy, UFPR, Av. Pref. Lothario Meissner 632, Jardim Botânico, Federal University of Paraná, 80210-170, Curitiba, Paraná, Brasil

    Daniela Regina Buch Leite, Solange Pereira Cordeiro, Filipe Barros Maia, Fernando Cesar Martins Betim, Elisiane de Bona Sartor, Deise Prehs Montrucchio, Josiane de Fátima Gaspari Dias, Obdulio Gomes Miguel & Marilis Dallarmi Miguel

  2. Institut de Chimie des Milieux et Matériaux de Poitiers (IC2MP) CNRS 7285, Department of Chemistry, B27-4, rue Michel Brunet-TSA, Université de Poitiers, 51106-86073, Poitiers, Cedex 9, France

    Karen Mary Mantovani

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Leite, D.R.B., Mantovani, K.M., Cordeiro, S.P. et al. RNA-dependent RNA polymerase (RdRp) natural antiviral inhibitors: a review. Med Chem Res 31, 2089–2102 (2022). https://doi.org/10.1007/s00044-022-02963-2

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