Abstract
Mortality and morbidity associated with COVID-19 continue to be significantly high worldwide, owing to the absence of effective treatment strategies. The emergence of different variants of SARS-CoV-2 is also a considerable source of concern and has led to challenges in the development of better prevention and treatment strategies, including vaccines. Immune dysregulation due to pro-inflammatory mediators has worsened the situation in COVID-19 patients. Inflammasomes play a critical role in modulating pro-inflammatory cytokines in the pathogenesis of COVID-19 and their activation is associated with poor clinical outcomes. Numerous preclinical and clinical trials for COVID-19 treatment using different approaches are currently underway. Targeting different inflammasomes to reduce the cytokine storm, and its associated complications, in COVID-19 patients is a new area of research. Non-coding RNAs, targeting inflammasome activation, may serve as an effective treatment strategy. However, the efficacy of these therapeutic agents is highly dependent on the delivery system. MicroRNAs and long non-coding RNAs, in conjunction with an efficient delivery vehicle, present a potential strategy for regulating NLRP3 activity through various RNA interference (RNAi) mechanisms. In this regard, the use of nanomaterials and other vehicle types for the delivery of RNAi-based therapeutic molecules for COVID-19 may serve as a novel approach for enhancing drug efficacy. The present review briefly summarizes immune dysregulation and its consequences, the roles of different non-coding RNAs in regulating the NLRP3 inflammasome, distinct types of vectors for their delivery, and potential therapeutic targets of microRNA for treatment of COVID-19.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease, 2019 (COVID-19), which first originated in the Chinese city ofWuhan and has since claimed the lives of over 5.1 million individuals worldwide [1]
The innate NLRP3 inflammasome immune signal receptor is involved in the cleavage and activation of pro-inflammatory cytokines that lead to the activation of inflammatory molecules such as IL-1β and active caspase 1
Expressed gene 3 (MEG-3) is another long non-coding RNAs (lncRNAs) transcript that influences the regulation of the NLRP3 inflammasome by neutralizing the inhibitory effects of miR-223 on inflammasome activation [153]
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease, 2019 (COVID-19), which first originated in the Chinese city of. Viral entry into the host is facilitated by the binding of a viral S protein to angiotensin-converting enzyme 2 (ACE2) receptors on lung cells Both structural and non-structural SARS-CoV-2 proteins have been associated with inflammasome activation and accompanying inflammation. Among the short ncRNAs, the endogenous singlestranded microRNAs (miRNAs), 18–24 nucleotides in length, play a critical role in disease progression, based on their potential to regulate gene expression at different levels [11] These miRNAs target several genes and other components [12] and can positively regulate NLRP3 inflammasome activation by promoting the assembly of NLRP3 components, neutralizing the inhibitory effects of certain miRNAs, and enhancing the expression of pro-inflammatory genes [13,14,15].
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