A computational approach to design potential siRNA molecules as a prospective tool for silencing nucleocapsid phosphoprotein and surface glycoprotein gene of SARS-CoV-2

Genomics. 2021 Jan;113(1 Pt 1):331-343. doi: 10.1016/j.ygeno.2020.12.021. Epub 2020 Dec 13.

Abstract

An outbreak, caused by an RNA virus, SARS-CoV-2 named COVID-19 has become pandemic with a magnitude which is daunting to all public health institutions in the absence of specific antiviral treatment. Surface glycoprotein and nucleocapsid phosphoprotein are two important proteins of this virus facilitating its entry into host cell and genome replication. Small interfering RNA (siRNA) is a prospective tool of the RNA interference (RNAi) pathway for the control of human viral infections by suppressing viral gene expression through hybridization and neutralization of target complementary mRNA. So, in this study, the power of RNA interference technology was harnessed to develop siRNA molecules against specific target genes namely, nucleocapsid phosphoprotein gene and surface glycoprotein gene. Conserved sequence from 139 SARS-CoV-2 strains from around the globe was collected to construct 78 siRNA that can inactivate nucleocapsid phosphoprotein and surface glycoprotein genes. Finally, based on GC content, free energy of folding, free energy of binding, melting temperature, efficacy prediction and molecular docking analysis, 8 siRNA molecules were selected which are proposed to exert the best action. These predicted siRNAs should effectively silence the genes of SARS-CoV-2 during siRNA mediated treatment assisting in the response against SARS-CoV-2.

Keywords: Nucleocapsid phosphoprotein; SARS-CoV-2; Surface glycoprotein; siDirect; siRNA.

MeSH terms

  • Argonaute Proteins / chemistry
  • Argonaute Proteins / genetics
  • Base Composition
  • COVID-19 / therapy*
  • COVID-19 / virology
  • COVID-19 Drug Treatment
  • Computational Chemistry*
  • Coronavirus Nucleocapsid Proteins / genetics*
  • Drug Design*
  • Evolution, Molecular
  • Gene Expression Regulation, Viral / drug effects
  • Genetic Therapy / methods*
  • Humans
  • Molecular Docking Simulation*
  • Pandemics
  • Phosphoproteins / genetics
  • Phylogeny
  • RNA Folding
  • RNA Interference*
  • RNA, Messenger / antagonists & inhibitors*
  • RNA, Messenger / genetics
  • RNA, Small Interfering / chemistry*
  • RNA, Small Interfering / pharmacology
  • RNA, Small Interfering / therapeutic use
  • RNA, Viral / antagonists & inhibitors*
  • RNA, Viral / genetics
  • SARS-CoV-2 / drug effects
  • SARS-CoV-2 / genetics*
  • Sequence Alignment
  • Spike Glycoprotein, Coronavirus / genetics*
  • Thermodynamics

Substances

  • AGO2 protein, human
  • Argonaute Proteins
  • Coronavirus Nucleocapsid Proteins
  • Phosphoproteins
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA, Viral
  • Spike Glycoprotein, Coronavirus
  • nucleocapsid phosphoprotein, SARS-CoV-2
  • spike protein, SARS-CoV-2