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

Author(s)

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]

Affiliation

^[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

• Document type: Review article
• Source: Viruses-Basel; v. 12, n. 6 JUN 2020.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 16/19712-9 - Structural characterization of Zika virus proteins and search for antiviral agents
• Grantee: Andre Schutzer de Godoy
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/05130-3 - Construction and characterization of a ZIKV sub-genomic replicon system for the discovery of antiviral agents.
• Grantee: Rafaela Sachetto Fernandes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 18/17095-8 - Structural characterization of the Chikungunya Virus NSP4 RNA-dependent RNA polymerase and search for antiviral agents
• Grantee: Marjorie Caroline Liberato Cavalcanti Freire
• Support Opportunities: Scholarships in Brazil - Doctorate