Reporter Replicons for Antiviral Drug Discovery against Positive Single-Stranded RNA Viruses

Autor(es)

Fernandes, Rafaela S. ^[1] ; Freire, Marjorie C. L. C. ^[1] ; Bueno, V, Renata ; Godoy, Andre S. ^[2] ; Gil, Laura H. V. G. ^[3] ; Oliva, Glaucius ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Phys Inst Sao Carlos, BR-13566590 Sao Carlos, SP - Brazil

^[2] Bueno, Renata, V, Univ Sao Paulo, Phys Inst Sao Carlos, BR-13566590 Sao Carlos, SP - Brazil

^[3] IAM FIOCRUZ, Inst Aggeu Magalhaes, BR-50670420 Recife, PE - Brazil

• Tipo de documento: Artigo de Revisão
• Fonte: Viruses-Basel; v. 12, n. 6 JUN 2020.
• Citações Web of Science: 0

Resumo

Single-stranded positive RNA ((+) ssRNA) viruses include several important human pathogens. Some members are responsible for large outbreaks, such as Zika virus, West Nile virus, SARS-CoV, and SARS-CoV-2, while others are endemic, causing an enormous global health burden. Since vaccines or specific treatments are not available for most viral infections, the discovery of direct-acting antivirals (DAA) is an urgent need. Still, the low-throughput nature of and biosafety concerns related to traditional antiviral assays hinders the discovery of new inhibitors. With the advances of reverse genetics, reporter replicon systems have become an alternative tool for the screening of DAAs. Herein, we review decades of the use of (+) ssRNA viruses replicon systems for the discovery of antiviral agents. We summarize different strategies used to develop those systems, as well as highlight some of the most promising inhibitors identified by the method. Despite the genetic alterations introduced, reporter replicons have been shown to be reliable systems for screening and identification of viral replication inhibitors and, therefore, an important tool for the discovery of new DAAs. (AU)

• Processo FAPESP: 16/19712-9 - Caracterização estrutural das proteínas do vírus Zika e busca por agentes antivirais
• Beneficiário: Andre Schutzer de Godoy
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 18/05130-3 - Construção e caracterização de um sistema replicon sub-genômico do ZIKV para a descoberta de agentes antivirais.
• Beneficiário: Rafaela Sachetto Fernandes
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/07600-3 - CIBFar - Centro de Inovação em Biodiversidade e Fármacos
• Beneficiário: Glaucius Oliva
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 18/17095-8 - Caracterização estrutural da proteína NSP4 RNA polimerase RNA-dependente do Vírus Chikungunya e busca por agentes antivirais
• Beneficiário: Marjorie Caroline Liberato Cavalcanti Freire
• Modalidade de apoio: Bolsas no Brasil - Doutorado