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

• Published in: Genomics (San Diego, Calif.) Calif.), 2021-01, Vol.113 (1), p.331-343
• Main Authors: Chowdhury, Umar Faruq, Sharif Shohan, Mohammad Umer, Hoque, Kazi Injamamul, Beg, Mirza Ashikul, Sharif Siam, Mohammad Kawsar, Moni, Mohammad Ali
• Format: Article
• Language: English
• Subjects: Argonaute Proteins - chemistry; Argonaute Proteins - genetics; Base Composition; Computational Chemistry; Coronavirus Nucleocapsid Proteins - genetics; COVID-19 - therapy; COVID-19 - virology; COVID-19 Drug Treatment; Drug Design; Evolution, Molecular; Gene Expression Regulation, Viral - drug effects; Genetic Therapy - methods; Humans; Molecular Docking Simulation; Nucleocapsid phosphoprotein; Original; 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; SARS-CoV-2 - drug effects; SARS-CoV-2 - genetics; Sequence Alignment; siDirect; siRNA; Spike Glycoprotein, Coronavirus - genetics; Surface glycoprotein; Thermodynamics
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1016/j.ygeno.2020.12.021

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. •We Identified and Validated siRNA molecules that are predicted to be highly effective and cleave specified mRNA•In-silico structural modelling was done for all 8 siRNA•Interaction with argounaute protein classified the siRNAs in two groups•This study might help to lead diversified approach to develop new and effective therapeutics against SARS-COV-2