MiRNA-SARS-CoV-2 dialogue and prospective anti-COVID-19 therapies

Abstract

COVID-19 is a highly transmissible disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), affects 226 countries and continents, and has resulted in >6.2 million deaths worldwide. Despite the efforts of all scientific institutions worldwide to identify potential therapeutics, no specific drug has been approved by the FDA to treat the COVID-19 patient. SARS-CoV-2 variants of concerns make the potential of publicly known therapeutics to respond to and detect disease onset highly improbable. The quest for universal therapeutics pointed to the ability of RNA-based molecules to shield and detect the adverse effects of the COVID-19 illness. One such candidate, miRNA (microRNA), works on regulating the differential expression of the target gene post-transcriptionally. The prime focus of this review is to report the critical miRNA molecule and their regular expression in patients with COVID-19 infection and associated comorbidities. Viral and host miRNAs control the etiology of COVID-19 infection throughout the life cycle and host inflammatory response, where host miRNAs are identified as a double-edged showing as a proviral and antiviral response. The review also covered the role of viral miRNAs in mediating host cell signaling expression during disease pathology. Studying molecular interactions between the host and the SARS-CoV-2 virus during COVID-19 pathogenesis offers the chance to use miRNA-based therapeutics to reduce the severity of the illness. By utilizing an appropriate delivery vehicle, these small non-coding RNA could be envisioned as a promising biomarker in designing a practical RNAi-based treatment approach of clinical significance.

Keywords: Biomarker; MiRNA; Pathogen-host interaction; RNA silencing; SARS coronavirus 2.

Graphical abstract

Fig. 1

Schematic mode of the interplay between human miRNA and SARS CoV-2 viral miRNA in COVID-19 infected individuals. (A) Conventional mechanism of eukaryotic host miRNA biogenesis and regulation of host gene expression. (B) The life cycle of SARS-CoV-2 virus with possible means of SARS-CoV-2 genome integration in the host cell and contribution of SARS-CoV-2 virus miRNAs to the manifestation of viral infection 1) virus attachment to host cell receptors (ACE-2) via its spike glycoprotein to penetrate the host cell. 2) Viral replication and host miRNA response alternation, as well as the maintenance of miRNA targeting sites in the viral genome 3) synthesis and discharge of new viruses to invade unaffected host tissues. 4) Ultimately, triggering the immunosuppression followed by a hyperinflammatory response in the host body.

Fig. 2

SARS-CoV-2 encoded miRNAs present in human serum during COVID-19 infection , , , , , , , , , , , , , , , , , , , , , , , .

Fig. 3

Expression of human derived miRNAs during SARS CoV-2 infection , , , , , , , , , , , , , , , , .

Fig. 4

Differential miRNA as biomarkers in COVID-19 infected patients with various comorbidities.

Fig. 5

Currently available delivery vehicle for the effective administration of miRNA-based therapeutics. It could be categorized broadly into viral and non-viral vectors. 1) Viral vector includes Lentiviruses, Bacteriophages, and Retroviruses. 2) Non-viral vector is further categorized into physical and chemical vectors. (i) Physical vector (biolistic gun, electroporation, ultrasound, etc.) (ii) chemical vector could be (a) inorganic material like gold nanoparticles (AuNPs), Fe3O4-based nanoparticles, silica-based nanoparticles, or magnetic nanoparticles; (b) polymeric vector such as polyethyleneimine (PEI), poly (lactic-co-glycolic acid) (PLGA), and dendrimers; (c) lipid-based nanocarriers like cationic, anionic, and neutral liposomes; (d) cell-derived membrane vesicles viz. Exosomes, microvesicles, or apoptotic bodies; lastly, (e) 3D scaffold based carrier comprises porous, fibrous scaffolds, etc. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)