An aptamer/ siRNA Chimera against The SARS-CoV-2: A Dual Therapeutic Strategy for The Virus Neutralizing and RNA Interfering

Abstract

During the ongoing COVID-19 pandemic, besides the vaccines, there is an urgent need for the development of effective therapeutics. Although significant efforts have been made to develop such therapies, there are currently no approved treatments for COVID-19. One of the potential therapeutic targets is the spike (S) protein of SARS-CoV-2, which mediates viral entry into host cells. It has been shown that targeting S protein could neutralize viruses and hinder their binding to the cells. Among known viral neutralizing agents, aptamers’ potential in neutralizing the SARS-Cov-2 virus has not yet been revealed. In addition, aptamers could also be used for targeted delivery of drugs and other genetic elements, such as siRNAs, to the cells. Small interfering RNAs (siRNAs) are reliable tools for gene knockdown via RNA degradation. siRNAs have been implemented previously against some viruses, including SARS-CoV, to target its genome. Recently, potential siRNA sequences and their targets in the SARS-CoV-2 genome have been reported, and the efficiency of siRNAs in inhibiting SARS-CoV-2 infection is being revealed. An alternative antiviral approach we propose here relies on an aptamer-siRNA-based system for the treatment of COVID-19. These aptamers could neutralize viruses by hindering their receptor-mediated endocytosis, and siRNAs could suppress the expression of viral genes and halt various aspects of its pathogenesis whenever the aptamers fail to neutralize the virus.

In silico prediction and experimental evaluation of potential siRNAs against SARS-CoV-2 inhibition in Vero E6 cells

“…Additionally, the designing of advanced siRNAs, aptamers/siRNAs chimera, siRNA-Nanoparticle, siRNA-peptide dendrimer formulation based therapy against SARS-CoV-2 using various genes and leader sequences have recently been reported and discussed in many published reports ( Panda et al, 2020 , Chen et al, 2020 , Bappy et al, 2021 , Khanali et al, 2020 , Shawan et al, 2021 , Chowdhury et al, 2021 , Idris et al, 2021 , Pandey and Verma, 2021 , Wu and Luo, 2021 , Rohani et al, 2021 , Khaitov et al, 2021 , Sohrab et al, 2021a , Sohrab et al, 2021b ). But most of the above published reports discussed only the prediction and designing of potential siRNAs, except only one report has discussed the designing and experimental evaluation of a few siRNAs against SARS-CoV-2 and found significant antiviral efficacy in Vero cells ( Niktab et al, 2021 ).…”