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Updated: Jan 18, 2026

High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses
Published on: May 5, 2014
RNAi therapy targeting coronavirus genomes, pulmonary delivery strategies and design principles: A review
Hao Shen1, Dongwan Cheng2, Liqing Liu3
1Genetic Skin Disease Center, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, 210042, Jiangsu, China.
Abstract:
With the persistent global outbreak of Coronavirus Disease 2019 (COVID-19), the development of effective antiviral strategies has become a top priority in public health. RNA interference (RNAi), an effective gene-silencing technique, presents a novel therapeutic approach to combat coronavirus replication. RNA interference (RNAi) is a potent gene-silencing approach that offers a therapeutic route to suppress coronavirus replication. Clinical translation of small interfering RNA (siRNA), however, faces substantial obstacles, notably cross-strain universality, off-target effects, and targeted delivery. This review summarizes recent advances in RNAi-mediated inhibition of coronaviruses at the genomic level, emphasizing RNAi applications to impede SARS-CoV-2 replication and transmission. By evaluating RNAi strategies aimed at specific viral components-RNA-dependent RNA polymerase (RdRp), spike protein (S), envelope protein (E), membrane protein (M), nucleocapsid protein (N), and other essential genes-we illustrate the distinct specificity and efficacy of RNAi across binding sites and identify candidate universal targets for human-transmitted coronaviruses. We also assess the strengths and limitations of delivery platforms, including liposomes, polymers, nanoparticles, and viral vectors. Finally, we highlight inhalation-based and other targeted delivery approaches as promising routes for siRNA therapeutics against COVID-19 and other pulmonary diseases. Advances in gene editing and nanotechnology continue to broaden the prospects for effective siRNA delivery.
Insights
RNA interference (RNAi) offers a promising therapeutic strategy to combat coronaviruses like COVID-19 by silencing viral genes. Advances in delivery methods, such as inhalation, enhance the potential of small interfering RNA (siRNA) therapeutics.
Area of Science:
- Molecular Biology
- Virology
- Biotechnology
Background:
- The COVID-19 pandemic highlights the urgent need for effective antiviral therapies.
- RNA interference (RNAi) presents a novel approach for gene silencing to inhibit viral replication.
- Clinical application of small interfering RNA (siRNA) faces challenges including delivery and specificity.
Purpose of the Study:
- To review recent advancements in RNAi-mediated inhibition of coronaviruses, focusing on SARS-CoV-2.
- To evaluate RNAi strategies targeting specific viral components and identify universal targets.
- To assess various delivery platforms and targeted delivery methods for siRNA therapeutics.
Main Methods:
- Review of current literature on RNAi applications against coronaviruses.
- Analysis of RNAi efficacy against different viral targets (RdRp, S, E, M, N proteins).
- Evaluation of delivery systems: liposomes, polymers, nanoparticles, and viral vectors.
Main Results:
- RNAi demonstrates specificity and efficacy against various viral components, with potential for universal targets.
- Inhalation-based delivery shows promise for pulmonary diseases, including COVID-19.
- Nanotechnology and gene editing are expanding possibilities for effective siRNA delivery.
Conclusions:
- RNAi is a viable therapeutic strategy against coronaviruses, with ongoing research addressing delivery and specificity challenges.
- Targeted delivery systems, particularly inhalation, are crucial for advancing siRNA therapeutics for respiratory viral infections.
- Continued innovation in gene editing and nanotechnology will likely enhance the effectiveness of RNAi-based treatments.
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