AI Article Synopsis
- The COVID-19 pandemic, caused by SARS-CoV-2, has highlighted the need for new treatments due to the emergence of resistant variants that make current vaccines and therapies insufficient.
- Researchers developed RNA replicons, which are safe versions of the virus that can be used in labs to test antiviral drugs without producing infectious virus particles.
- The study involved creating and testing three different RNA replicons, particularly the Δorf2.4-puro, which showed prolonged replication under selection pressure, aiding in the potential development of new antiviral medications.
Article Abstract
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has necessitated the global development of countermeasures since its outbreak. However, current therapeutics and vaccines to stop the pandemic are insufficient and this is mainly because of the emergence of resistant variants, which requires the urgent development of new countermeasures, such as antiviral drugs. Replicons, self-replicating RNAs that do not produce virions, are a promising system for this purpose because they safely recreate viral replication, enabling antiviral screening in biosafety level (BSL)-2 facilities. We herein constructed three pCC2Fos-based RNA replicons lacking some open reading frames (ORF) of SARS-CoV-2: the Δorf2-8, Δorf2.4, and Δorf2 replicons, and validated their replication in Huh-7 cells. The functionalities of the Δorf2-8 and Δorf2.4 replicons for antiviral drug screening were also confirmed. We conducted puromycin selection following the construction of the Δorf2.4-puro replicon by inserting a puromycin-resistant gene into the Δorf2.4 replicon. We observed the more sustained replication of the Δorf2.4-puro replicon by puromycin pressure. The present results will contribute to the establishment of a safe and useful replicon system for analyzing SARS-CoV-2 replication mechanisms as well as the development of novel antiviral drugs in BSL-2 facilities.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10374963 | PMC |
| http://dx.doi.org/10.1016/j.virusres.2023.199176 | DOI Listing |
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