Related Experiment Video
Updated: Aug 12, 2025
11:34
High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses
Published on: May 5, 2014
13.9K
Targeting RNA G-quadruplex with repurposed drugs blocks SARS-CoV-2 entry
Qiyu Tong1, Geng Liu1, Xiongbo Sang1
1Division of Endocrinology and Metabolism, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, China.
Plos Pathogens
|January 26, 2023
Summary
Researchers identified RNA G-quadruplexes (RG4s) in SARS-CoV-2 host factors. Two drugs, Topotecan and Berbamine, stabilize RG4s, blocking viral entry and offering a potential broad-spectrum COVID-19 antiviral strategy.
Area of Science:
- Molecular Biology
- Virology
- Drug Discovery
Background:
- The COVID-19 pandemic necessitates broad-spectrum antivirals due to SARS-CoV-2 variants and complex host interactions.
- Drug repurposing is a promising strategy for rapid therapeutic development against emerging viral threats.
Purpose of the Study:
- To investigate RNA G-quadruplexes (RG4s) as potential targets for inhibiting SARS-CoV-2 entry.
- To identify existing drugs that can stabilize RG4s in host factors crucial for viral infection.
Main Methods:
- Bioinformatics, biochemical, and biophysical approaches were used to characterize RG4s in host factors.
- In silico screening followed by experimental validation identified Topotecan (TPT) and Berbamine (BBM) as RG4-stabilizing agents.
- Assays were performed to assess the effect of TPT and BBM on host factor protein levels and SARS-CoV-2 pseudovirus entry in vitro and in vivo.
Main Results:
- RG4s were identified in key SARS-CoV-2 host factors, including ACE2, AXL, FURIN, and TMPRSS2.
- Topotecan and Berbamine were confirmed as RG4-stabilizing agents with repurposing potential for COVID-19.
- Both drugs effectively reduced the protein levels of RG4-containing host factors and inhibited SARS-CoV-2 pseudovirus entry into cells and tissues.
Conclusions:
- RG4s play a significant role in SARS-CoV-2 pathogenesis.
- RG4-targeting agents like Topotecan and Berbamine represent a potential broad-spectrum antiviral strategy for COVID-19 prevention and treatment.
More Related Videos
Related Concept Videos
01:23RNA Interference
26.3K
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
26.3K
02:15Experimental RNAi
6.2K
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
6.2K
02:30siRNA - Small Interfering RNAs
16.9K
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
16.9K
01:29Viruses with RNA Genomes
76
RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
76
02:28Leaky Scanning
5.2K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.2K