气候变化领域集成服务门户(CCPortal): Generation of sars-cov-2 reporter replicon for high-throughput antiviral screening and testing

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DOI	10.1073/PNAS.2025866118
	Generation of sars-cov-2 reporter replicon for high-throughput antiviral screening and testing
	He X.; Quan S.; Xu M.; Rodriguez S.; Goh S.L.; Wei J.; Fridman A.; Koeplinger K.A.; Carroll S.S.; Grobler J.A.; Espeseth A.S.; Olsen D.B.; Hazuda D.J.; Wang D.
发表日期	2021
ISSN	00278424
卷号	118 期号:15
英文摘要	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) research and antiviral discovery are hampered by the lack of a cellbased virus replication system that can be readily adopted without biosafety level 3 (BSL-3) restrictions. Here, the construction of a noninfectious SARS-CoV-2 reporter replicon and its application in deciphering viral replication mechanisms and evaluating SARS-CoV-2 inhibitors are presented. The replicon genome is replication competent but does not produce progeny virions. Its replication can be inhibited by RdRp mutations or by known SARS-CoV-2 antiviral compounds. Using this system, a high-throughput antiviral assay has also been developed. Significant differences in potencies of several SARS-CoV-2 inhibitors in different cell lines were observed, which highlight the challenges of discovering antivirals capable of inhibiting viral replication in vivo and the importance of testing compounds in multiple cell culture models. The generation of a SARS-CoV-2 replicon provides a powerful platform to expand the global research effort to combat COVID-19. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Antivirals; COVID-19; High-throughput antiviral screening; Replicon; SARS-CoV-2
语种	英语
scopus关键词	antivirus agent; apilimod; boceprevir; camostat; gc 373; gc 376; gs 441524; mk 3034; nafamstat; pf 00835231; relacatib; remdesivir; RNA directed RNA polymerase; unclassified drug; antivirus agent; NSP12 protein, SARS-CoV-2; A-549 cell line; animal cell; antiviral susceptibility; Article; drug potency; drug screening; embryo; gene mutation; HEK293 cell line; high throughput screening; Huh-7.5 cell line; human; human cell; in vitro study; nonhuman; nucleotide sequence; priority journal; progeny; replicon cell; Severe acute respiratory syndrome coronavirus 2; squamous cell carcinoma cell line; virion; virus replication; animal; Chlorocebus aethiops; drug effect; genetics; high throughput screening; procedures; replicon; Vero cell line; virology; virus replication; A549 Cells; Animals; Antiviral Agents; Chlorocebus aethiops; Coronavirus RNA-Dependent RNA Polymerase; COVID-19; HEK293 Cells; High-Throughput Screening Assays; Humans; Replicon; SARS-CoV-2; Vero Cells; Virus Replication
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179945
作者单位	Infectious Disease and Vaccines, Merck and Company Inc., Kenilworth, NJ 07033, United States
推荐引用方式 GB/T 7714	He X.,Quan S.,Xu M.,et al. Generation of sars-cov-2 reporter replicon for high-throughput antiviral screening and testing[J],2021,118(15).
APA	He X..,Quan S..,Xu M..,Rodriguez S..,Goh S.L..,...&Wang D..(2021).Generation of sars-cov-2 reporter replicon for high-throughput antiviral screening and testing.Proceedings of the National Academy of Sciences of the United States of America,118(15).
MLA	He X.,et al."Generation of sars-cov-2 reporter replicon for high-throughput antiviral screening and testing".Proceedings of the National Academy of Sciences of the United States of America 118.15(2021).