Institute of Pharmacy & Technology, Salipur, Cuttack, Odisha, 754202, India.
School of Pharmacy, The Neotia University, Sarisa, D.H. Road, 24 Pgs (South) West Bengal, 743368, India.
Future Med Chem. 2023 Jun;15(12):1091-1110. doi: 10.4155/fmc-2023-0091. Epub 2023 Aug 16.
Small-molecule oligonucleotides could be exploited therapeutically to silence the expression of viral infection-causing genes, and a few of them are now in clinical trials for the management of viral infections. The most challenging aspect of these oligonucleotides' therapeutic success involves their delivery. Thus medicinal chemistry strategies are inevitable to avoid degradation by serum nucleases, avoid kidney clearance and improve cellular uptake. Recently small-molecule oligonucleotide design has opened up new avenues to improve the treatment of drug-resistant viral infections, along with the development of COVID-19 medicines. This review is directed toward the recent advances in rational design, mechanism of action, structure-activity relationships and future perspective of the small-molecule oligonucleotides targeting viral infections, including COVID-19.
小分子寡核苷酸可以被开发为治疗药物来沉默导致病毒感染的基因的表达，其中有一些目前正在临床试验中用于治疗病毒感染。这些寡核苷酸治疗成功的最具挑战性的方面涉及它们的递送。因此，不可避免地需要药物化学策略来避免被血清核酸酶降解、避免肾脏清除并提高细胞摄取。最近，小分子寡核苷酸设计为治疗耐药性病毒感染开辟了新途径，同时也为 COVID-19 药物的发展提供了帮助。这篇综述主要针对针对病毒感染（包括 COVID-19）的小分子寡核苷酸的合理设计、作用机制、构效关系和未来前景的最新进展。
