DisCoVering potential candidates of RNAi-based therapy for COVID-19 using computational methods

Abstract

The ongoing pandemic of a novel coronavirus (SARS-CoV-2) leads to international concern; thus, emergency interventions need to be taken. Due to the time-consuming experimental methods for proposing useful treatments, computational approaches facilitate investigating thousands of alternatives simultaneously and narrow down the cases for experimental validation. Herein, we conducted four independent analyses for RNA interference (RNAi)-based therapy with computational and bioinformatic methods. The aim is to target the evolutionarily conserved regions in the SARS-CoV-2 genome in order to down-regulate or silence its RNA. miRNAs are denoted to play an important role in the resistance of some species to viral infections. A comprehensive analysis of the miRNAs available in the body of humans, as well as the miRNAs in bats and many other species, were done to find efficient candidates with low side effects in the human body. Moreover, the evolutionarily conserved regions in the SARS-CoV-2 genome were considered for designing novel significant siRNA that are target-specific. A small set of miRNAs and five siRNAs were suggested as the possible efficient candidates with a high affinity to the SARS-CoV-2 genome and low side effects. The suggested candidates are promising therapeutics for the experimental evaluations and may speed up the procedure of treatment design. Materials and implementations are available at: https://github.com/nrohani/SARS-CoV-2.

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

“…The RNAi technology has played a significant role and produced considerable results towards different diseases caused by various viruses ( Jeang, 2012 , Chakraborty et al, 2017 ). Currently, using RNAi technology, a significant number of siRNAs/shRNAs have been designed, developed, and experimentally evaluated and showed promising results against many viruses including MERS-CoV and SARS-CoV-2 against the multiple targets of a viral genome (Sohrab et al, 2018; Sohrab et al, 2020; Uludag et al, 2020; Panda et al, 2020 , Chen et al, 2020 , Sohrab et al, 2021a , Sohrab et al, 2021b ; Sherif Aly El-Kafrawy et al, 2021 , Khaitov et al, 2021 , Idris et al, 2021 , Pandey and Verma, 2021 , Donia and Bokhari, 2021 ; Bappy et a., 2021; Niktab et al, 2021 ; Khanali et al, 2021; Shawan et al, 2021 , Chowdhury et al, 2021 ; Wu and KQ, 2021; Rohani et al, 2021 , Khaitov et al, 2021 ). The SARS-CoV-2 uses the S protein to attach with host cells and many vaccines have been developed by using this target, but many variants have been emerged globally by mutations in the Spike (S) gene and making it difficult to develop vaccines and antivirals for broad-spectrum resistance against SARS-CoV-2 ( Harvey et al, 2021 , Greaney et al, 2021 , Khateeb et al, 2021 , Starr et al, 2021 ; (https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/).…”

“…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 ).…”

Development and application of ribonucleic acid therapy strategies against COVID-19

“…In one attempt, siRNAs were designed to directly target the evolutionarily conserved regions in the SARS-CoV-2 genome to down-regulate or silence its RNA. These siRNA candidates which had high affinity and low side effects were considered to be the potential therapeutics 143 .…”

microRNAs and Inflammatory Immune Response in SARS-CoV-2 Infection: A Narrative Review

“…In a review of Abedi et al [70], several miRNAs involved in the inflammatory response to SARS-CoV-2 infection are suggested as potentially useful against the inflammatory cascade, in cytokine storm attenuation and in acute lung injury reduction. Rohani et al [71] explored the CLASH database, which contains validated interactions between human miRNAs and human mRNAs, to identify host miRNAs with a therapeutic potential, that may have efficient interactions with SARS-CoV-2 unstructured conserved regions (UCRs) and a low affinity to human mRNAs. A total of seven candidate miRNAs (hsa-miR-374a-5p, hsa-miR-548b-3p, hsa-miR-1-3p, hsa-miR-224-5p, hsa-miR-98-5p, hsa-miR-26a-2-3p, hsa-miR-192-3p) potentially targeting several SARS-CoV-2 UCRs, could facilitate antiviral IFN-β immune response, prevention of cell autophagy and degradation of viral components.…”