tetano
Editor, Senior Moderator
Gene Rep
. 2022 Mar;26:101512.
doi: 10.1016/j.genrep.2022.101512. Epub 2022 Jan 15.
RNAi-mediated siRNA sequences to combat the COVID-19 pandemic with the inhibition of SARS-CoV2
Khandakar A S M Saadat[SUP] 1 2 [/SUP]
Affiliations
Abstract
The outbreak of the COVID-19 pandemic has cost five million lives to date, and was caused by a positive-sense RNA virus named SARS-CoV2. The lack of drugs specific to SARS-CoV2, leads us to search for an effective and specific therapeutic approach. Small interfering RNA (siRNA) is able to activate the RNA interference (RNAi) pathway to silence the specific targeted gene and inhibit the viral replication, and it has not yet attracted enough attention as a SARS-CoV2 antiviral agent. It could be a potential weapon to combat this pandemic until the completion of full scale, effective mass vaccination. For this study, specific siRNAs were designed using a web-based bioinformatics tool (siDirect2.0) against 14 target sequences. These might have a high probability of silencing the essential proteins of SARS-CoV2. such as: 3CLpro/Mpro/nsp5, nsp7, Rd-Rp/nsp12, ZD, NTPase/HEL or nsp13, PLpro/nsp3, envelope protein (E), spike glycoprotein (S), nucleocapsid phosphoprotein (N), membrane glycoprotein (M), ORF8, ORF3a, nsp2, and its respective 5' and 3'-UTR. Among these potential drug targets, the majority of them contain highly conserved sequences; the rest are chosen on the basis of their role in viral replication and survival. The traditional vaccine development technology using SARS-CoV2 protein takes 6-8 months; meanwhile the virus undergoes several mutations in the candidate protein chosen for vaccine development. By the time the protein-based vaccine reaches the market, the virus would have undergone several mutations, such that the antibodies against the viral sequence may not be effective in restricting the newly mutated viruses. However, siRNA technology can make sequences based on real time viral mutation status. This has the potential for suppressing SARS-CoV2 viral replication, through RNAi technology.
Keywords: 3CLpro, 3-chymotrypsin like proteases; Antiviral; COVID-19, Coronavirus Disease of 2019; Drug design; MERS, Middle East Respiratory Syndrome; Mpro, main proteases; ORF, open reading frame; PLpro, papain like proteases; RNAi; RNAi, RNA interference; Rd-Rp, RNA dependent-RNA polymerases; SARS, severe acute respiratory syndrome; SARS-CoV2; SARS-CoV2, severe acute respiratory syndrome coronavirus 2; Therapeutics; UTR, untranslated region; nsp, non-structural protein; siRNA; siRNA, small interfering RNA.
. 2022 Mar;26:101512.
doi: 10.1016/j.genrep.2022.101512. Epub 2022 Jan 15.
RNAi-mediated siRNA sequences to combat the COVID-19 pandemic with the inhibition of SARS-CoV2
Khandakar A S M Saadat[SUP] 1 2 [/SUP]
Affiliations
- PMID: 35071824
- PMCID: PMC8760737
- DOI: 10.1016/j.genrep.2022.101512
Abstract
The outbreak of the COVID-19 pandemic has cost five million lives to date, and was caused by a positive-sense RNA virus named SARS-CoV2. The lack of drugs specific to SARS-CoV2, leads us to search for an effective and specific therapeutic approach. Small interfering RNA (siRNA) is able to activate the RNA interference (RNAi) pathway to silence the specific targeted gene and inhibit the viral replication, and it has not yet attracted enough attention as a SARS-CoV2 antiviral agent. It could be a potential weapon to combat this pandemic until the completion of full scale, effective mass vaccination. For this study, specific siRNAs were designed using a web-based bioinformatics tool (siDirect2.0) against 14 target sequences. These might have a high probability of silencing the essential proteins of SARS-CoV2. such as: 3CLpro/Mpro/nsp5, nsp7, Rd-Rp/nsp12, ZD, NTPase/HEL or nsp13, PLpro/nsp3, envelope protein (E), spike glycoprotein (S), nucleocapsid phosphoprotein (N), membrane glycoprotein (M), ORF8, ORF3a, nsp2, and its respective 5' and 3'-UTR. Among these potential drug targets, the majority of them contain highly conserved sequences; the rest are chosen on the basis of their role in viral replication and survival. The traditional vaccine development technology using SARS-CoV2 protein takes 6-8 months; meanwhile the virus undergoes several mutations in the candidate protein chosen for vaccine development. By the time the protein-based vaccine reaches the market, the virus would have undergone several mutations, such that the antibodies against the viral sequence may not be effective in restricting the newly mutated viruses. However, siRNA technology can make sequences based on real time viral mutation status. This has the potential for suppressing SARS-CoV2 viral replication, through RNAi technology.
Keywords: 3CLpro, 3-chymotrypsin like proteases; Antiviral; COVID-19, Coronavirus Disease of 2019; Drug design; MERS, Middle East Respiratory Syndrome; Mpro, main proteases; ORF, open reading frame; PLpro, papain like proteases; RNAi; RNAi, RNA interference; Rd-Rp, RNA dependent-RNA polymerases; SARS, severe acute respiratory syndrome; SARS-CoV2; SARS-CoV2, severe acute respiratory syndrome coronavirus 2; Therapeutics; UTR, untranslated region; nsp, non-structural protein; siRNA; siRNA, small interfering RNA.