Nedaeinia Reza, Ranjbar Maryam, Goli Mohammad, Etebari Mahmoud, Safabakhsh Saied, Bayram Hasan, Ferns Gordon A, Tehrani Helena Moradiyan, Salehi Rasoul
Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Materials Engineering, Advanced Materials Research Center, Islamic Azad University, Najafabad Branch, Najafabad, Iran.
Curr Med Chem. 2025;32(6):1144-1167. doi: 10.2174/0109298673300236240529195835.
The evolution of novel Severe Acute Respiratory Syndrome-related Coronavirus 2 (SARS-CoV-2) strains with greater degrees of infectivity, resistance to vaccine-induced acquired immunity, and more severe morbidity have contributed to the recent spread of COVID-19. In light of this, novel therapeutic alternatives with improved effectiveness and fewer side effects have become a necessity. Despite many new or repurposed antiviral agents recommended for Coronavirus disease (COVID-19) therapy, this objective remains unfulfilled. Under these circumstances, the scientific community holds the significant responsibility to develop classes of novel therapeutic modalities to combat SARS-CoV-2 with the least harmful side effects.
Antisense Oligonucleotides (ASOs) are short single-stranded oligonucleotides that allow the specific targeting of RNA, leading to its degradation. They may also prevent cellular factors or machinery from binding to the target RNA. It is possible to improve the pharmacokinetics and pharmacodynamics of ASOs by chemical modification or bioconjugation, which may provide conditions for customization of a particular clinical target. This study aimed to outline the potential use of ASOs in the treatment of COVID-19 disease, along with the use of antisense stabilization and transfer methods, as well as future challenges and limitations.
We have reviewed the structure and properties of ASOs containing nucleobase, sugar, or backbone modifications, and provided an overview of the therapeutic potential, delivery challenges, and strategies of ASOs in the treatment of COVID-19.
The first-line therapy for COVID-19-infected individuals, as well as the development of oligonucleotide- based drugs, warrants further investigation. Chemical changes in the oligonucleotide structure can affect the biological processes. These chemical alterations may lead to enhanced potency, while changing the pharmacokinetics and pharmacodynamics.
ASOs can be designed to target both coding and non-coding regions of the viral genome to disrupt or completely degrade the genomic RNA and thereby eliminate SARS-CoV-2. They may be very effective in areas, where vaccine distribution is challenging, and they may be helpful for future coronavirus pandemics.
新型严重急性呼吸综合征相关冠状病毒2（SARS-CoV-2）毒株不断演变，其传染性更强、对疫苗诱导的获得性免疫具有抗性且发病率更高，导致了近期新冠病毒病（COVID-19）的传播。有鉴于此，开发疗效更佳且副作用更少的新型治疗方案成为必要。尽管有许多新的或重新利用的抗病毒药物被推荐用于冠状病毒病（COVID-19）治疗，但这一目标仍未实现。在这种情况下，科学界肩负着开发新型治疗方式以对抗SARS-CoV-2且副作用最小的重大责任。
反义寡核苷酸（ASO）是短的单链寡核苷酸，可特异性靶向RNA，导致其降解。它们还可能阻止细胞因子或机制与靶RNA结合。通过化学修饰或生物偶联可以改善ASO的药代动力学和药效学，这可能为针对特定临床靶点的定制提供条件。本研究旨在概述ASO在治疗COVID-19疾病中的潜在用途，以及反义稳定和传递方法的应用，以及未来的挑战和局限性。
我们回顾了含有核碱基、糖或主链修饰的ASO的结构和特性，并概述了ASO在治疗COVID-19中的治疗潜力、递送挑战和策略。
对于COVID-19感染个体的一线治疗以及基于寡核苷酸的药物开发，仍需进一步研究。寡核苷酸结构中的化学变化会影响生物学过程。这些化学改变可能会增强效力，同时改变药代动力学和药效学。
可以设计ASO靶向病毒基因组的编码和非编码区域，以破坏或完全降解基因组RNA，从而消除SARS-CoV-2。在疫苗分发具有挑战性的地区，它们可能非常有效，并且可能有助于应对未来的冠状病毒大流行。
