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siRNA as a Potential Therapy for COVID-19
Ahmad Aljaberi1, Eman M Migdadi1, Khalid M Abu Khadra2
1Department of Pharmaceutical Sciences and Pharmaceutics, Faculty of Pharmacy, Applied Science Private University, Amman, Jordan.
Abstract:
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) is a highly contagious virus causing COVID-19 disease that severely impacted the world health, education, and economy systems in 2020. The numbers of infection cases and reported deaths are still increasing with no specific treatment identified yet to halt this pandemic. Currently, several proposed treatments are under preclinical and clinical investigations now, alongside the race to vaccinate as many individuals as possible. The genome of SARS-CoV2 shares a similar gene organization as other viruses in the Coronaviridae family. It is a positive-sense, single-stranded RNA. This feature suggests that RNA interference (RNAi) is an attractive prophylactic and therapeutic option for the control of this pandemic and other possible future pandemics of the corona viruses. RNAi utilizes the use of siRNA molecules, which are 21-29 nt duplexes RNA molecules that intervene with targeted gene expression in the cytoplasm by a specific mechanism of complementary destruction of mRNA. Previous experience with SARS-CoV and the Middle East respiratory syndrome (MERS) showed that siRNA molecules were effective against these viruses in vitro and in vivo. Moreover, there have been extensive advances in siRNA technology in the past decade from chemistry and target selection considerations; which concluded with the successful approval of two commercial products based on siRNA technology. In addition, the current knowledge of the genome structure and functionality of the corona viruses enables the recognition of conserved sequences to optimize siRNA targeting and avoid viral escape through mutations, either for the current SARS-CoV2 as well as future corona viruses.
Insights
RNA interference (RNAi) offers a promising strategy against SARS-CoV-2. Small interfering RNA (siRNA) technology can target and destroy viral RNA, providing a potential treatment for COVID-19 and future coronavirus pandemics.
Area of Science:
- Virology
- Molecular Biology
- Biotechnology
Background:
- Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes COVID-19, a global pandemic with significant health and economic impacts.
- No specific antiviral treatment currently halts the pandemic, necessitating the exploration of novel therapeutic strategies.
- Coronaviruses, including SARS-CoV-2, possess a positive-sense, single-stranded RNA genome, making them susceptible to RNA interference.
Purpose of the Study:
- To evaluate RNA interference (RNAi) as a potential prophylactic and therapeutic approach against SARS-CoV-2.
- To highlight the suitability of small interfering RNA (siRNA) technology for controlling current and future coronavirus outbreaks.
- To leverage existing knowledge of coronavirus genomes for optimized siRNA targeting.
Main Methods:
- Utilizing small interfering RNA (siRNA) molecules, which are 21-29 nucleotide duplexes.
- Employing the RNAi mechanism for targeted gene silencing via complementary destruction of viral messenger RNA (mRNA) in the cytoplasm.
- Analyzing the conserved sequences within coronavirus genomes to optimize siRNA design and prevent viral escape mutations.
Main Results:
- Previous studies demonstrated the efficacy of siRNA against SARS-CoV and MERS-CoV in vitro and in vivo.
- Advances in siRNA technology have led to successful commercial product approvals, indicating platform maturity.
- Knowledge of coronavirus genome structure facilitates the identification of conserved target sequences for effective siRNA intervention.
Conclusions:
- RNA interference (RNAi) presents a viable therapeutic and prophylactic option for managing SARS-CoV-2 and future coronavirus pandemics.
- Optimized siRNA targeting, based on conserved viral sequences, can effectively combat viral RNA and mitigate mutation-driven escape.
- The established success of siRNA technology provides a strong foundation for its application against COVID-19.
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