Wu Renfei, Luo Kathy Qian
Faculty of Health Sciences, University of Macau, Macao SAR, China.
Int J Biol Sci. 2021 Apr 10;17(6):1521-1529. doi: 10.7150/ijbs.59151. eCollection 2021.
The COVID-19 pandemic has been raging worldwide for more than a year. Many efforts have been made to create vaccines and develop new antiviral drugs to cope with the disease. Here, we propose the application of short interfering RNAs (siRNAs) to degrade the viral genome, thus reducing viral infection. By introducing the concept of the probability of binding efficiency (PBE) and combining the secondary structures of RNA molecules, we designed 11 siRNAs that target the consensus regions of three key viral genes: the spike (S), nucleocapsid (N) and membrane (M) genes of SARS-CoV-2. The silencing efficiencies of the siRNAs were determined in human lung and endothelial cells overexpressing these viral genes. The results suggested that most of the siRNAs could significantly reduce the expression of the viral genes with inhibition rates above 50% in 24 hours. This work not only provides a strategy for designing potentially effective siRNAs against target genes but also validates several potent siRNAs that can be used in the clinical development of preventative medication for COVID-19 in the future.
新冠疫情已在全球肆虐一年多。人们为研发疫苗和开发新型抗病毒药物以应对该疾病付出了诸多努力。在此，我们提议应用短干扰RNA（siRNA）来降解病毒基因组，从而减少病毒感染。通过引入结合效率概率（PBE）的概念并结合RNA分子的二级结构，我们设计了11种靶向三个关键病毒基因共有区域的siRNA，这三个基因分别是严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的刺突（S）基因、核衣壳（N）基因和膜（M）基因。在过表达这些病毒基因的人肺细胞和内皮细胞中测定了这些siRNA的沉默效率。结果表明，大多数siRNA能够在24小时内显著降低病毒基因的表达，抑制率超过50%。这项工作不仅为设计针对靶基因的潜在有效siRNA提供了策略，还验证了几种强效siRNA，它们未来可用于新冠预防性药物的临床开发。
