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.
ABSTRACT
Mucociliary clearance, mediated by a coordinated function of cilia bathing in the airway surface liquid (ASL) on the surface of airway epithelium, protects the host from inhaled pathogens and is an essential component of the innate immunity. ASL is composed of the superficial mucus layer and the deeper periciliary liquid. Ion channels, transporters, and pumps coordinate the transcellular and paracellular movement of ions and water to maintain the ASL volume and mucus hydration. microRNA (miRNA) is a class of non-coding, short single-stranded RNA regulating gene expression by post-transcriptional mechanisms. miRNAs have been increasingly recognized as essential regulators of ion channels and transporters responsible for ASL homeostasis. miRNAs also influence the airway host defense. We summarize the most up-to-date information on the role of miRNAs in ASL homeostasis and host-pathogen interactions in the airway and discuss concepts for miRNA-directed therapy.