Developing effective siRNAs to reduce the expression of key viral genes of COVID-19

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.

Keywords: COVID-19; RNA secondary structure; SARS-CoV-2; gene silencing; siRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • COVID-19 / virology*
  • Gene Expression Regulation, Viral / physiology*
  • Genes, Viral*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Mutation
  • Probability
  • RNA, Small Interfering / physiology*
  • SARS-CoV-2 / genetics*
  • Spike Glycoprotein, Coronavirus / genetics


  • RNA, Small Interfering
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2