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.
【저자키워드】 Drug discovery, Direct-acting antivirals, replicon systems, (+) ssRNA viruses, 【초록키워드】 SARS-CoV-2, Vaccine, SARS-CoV, inhibitors, viral infections, genetics, RNA, biosafety, Outbreaks, Health, viral replication, Antiviral agents, Pathogens, inhibitor, reporter, antiviral assay, Endemic, West Nile Virus, Zika virus, specific treatment, positive, ssRNA, direct-acting antiviral, highlight, shown, responsible, develop, virus, include, introduced, genetic alteration, Still, 【제목키워드】 drug, RNA, replicon,