Single-step construction of a picornavirus replicon RNA with precise ends

Xiong, Qing; Wang, Yuya; Xie, Bing; Pei, Xinyi; Peng, Yiru

doi:10.1016/j.jviromet.2017.06.009

Cited by 3 publications

(3 citation statements)

References 26 publications

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“…The Picornaviridae is one of the largest viral families, classified in eight established and five proposed genera [ 80 ]. Picornaviruses are non-enveloped icosahedral viruses responsible for causing a variety of diseases going from mild respiratory illness (rhinoviruses) to acute flaccid paralysis—AFP (polioviruses) [ 81 ]. The viral genome of about 7.0 to 8.5 kb is composed of a single ORF flanked by 5′ and 3′ UTR’s and is covalently linked to the VPg (3B) at its 5′ terminus as well as polyadenylated at its 3′ terminus [ 82 ] ( Figure 3 a).…”

Section: Non-enveloped Virusesmentioning

confidence: 99%

“…The viral genome of about 7.0 to 8.5 kb is composed of a single ORF flanked by 5 and 3 UTR's and is covalently linked to the VPg (3B) at its 5 terminus as well as polyadenylated at its 3 terminus [82] (Figure 3a). The ORF encodes a single polyprotein, which, following synthesis, undergoes multiple cleavages by the two viral proteases 2A pro and 3C pro to produce the final mature viral capsid proteins and nonstructural proteins [81]. [83] for the Poliovirus (PV).…”

Section: Picornaviridae Familymentioning

confidence: 99%

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

Fernandes

Freire

Bueno

et al. 2020

Viruses

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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.

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Section: Non-enveloped Virusesmentioning

confidence: 99%

Section: Picornaviridae Familymentioning

confidence: 99%

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

Fernandes

Freire

Bueno

et al. 2020

Viruses

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“…This review will briefly cover the modern success story of the establishment and use of subgenomic replicons in the development of drugs against hepatitis C virus (HCV) and then illustrate the potential of dengue virus, togavirus, respiratory syncytial virus and norovirus replicons, and the Ebola virus minigenome, in the discovery of small-molecule inhibitors. In recent years replicons have been derived from viruses such as hepatitis E virus, enterovirus 71, severe acute respiratory syndrome virus, among others, but their description is beyond the scope of this review [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Viral replicons as valuable tools for drug discovery

Hannemann¹

2020

Drug Discovery Today

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RNA viruses can cause severe diseases such as dengue, Lassa, chikungunya and Ebola. Many of these viruses can only be propagated under high containment levels, necessitating the development of low containment surrogate systems such as subgenomic replicons and minigenome systems. Replicons are self-amplifying recombinant RNA molecules expressing proteins sufficient for their own replication but which do not produce infectious virions. Replicons can persist in cells and are passed on during cell division, enabling quick, efficient and high-throughput testing of drug candidates that act on viral transcription, translation and replication. This review will explore the history and potential for drug discovery of hepatitis C virus, dengue virus, respiratory syncytial virus, Ebola virus and norovirus replicon and minigenome systems.

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