Abstract
Coronavirus disease 2019 (COVID-19) has shaken the world and triggered drastic changes in our lifestyle to control it. Despite the non-typical efforts, COVID-19 still thrives and plagues humanity worldwide. The unparalleled degree of infection has been met with an exceptional degree of research to counteract it. Many drugs and therapeutic technologies have been repurposed and discovered, but no groundbreaking antiviral agent has been introduced yet to eradicate COVID-19 and restore normalcy. As lethality is directly correlated with the severity of disease, hospitalized severe cases are of the greatest importance to reduce, especially the cytokine storm phenomenon. This severe inflammatory phenomenon characterized by elevated levels of inflammatory mediators can be targeted to relieve symptoms and save the infected patients. One of the promising therapeutic strategies to combat COVID-19 is nucleic acid-based therapeutic approaches, including microRNAs (miRNAs). This work is an up-to-date review aimed to comprehensively discuss the current nucleic acid-based therapeutics against COVID-19 and their mechanisms of action, taking into consideration the emerging SARS-CoV-2 variants of concern, as well as providing potential future directions. miRNAs can be used to run interference with the expression of viral proteins, while endogenous miRNAs can be targeted as well, offering a versatile platform to control SARS-CoV-2 infection. By targeting these miRNAs, the COVID-19-induced cytokine storm can be suppressed. Therefore, nucleic acid-based therapeutics (miRNAs included) have a latent ability to break the COVID-19 infection in general and quell the cytokine storm in particular.
Highlights
The rapid spread of the novel coronavirus disease 2019 (COVID-19) has hit every corner of the world and has led to drastic changes in the lifestyle of humanity
MiR-125a-3p inhibits the cleavage of the S gene miR-138-5p inhibits the cleavage of the ORF1a/b polyprotein gene miR-21-3p expressed in respiratory epithelial cells in the trachea and lung tissues, which targets the binding site of 6 different coronavirus, including SARS-CoV-2 and SARS
Vaccinating hundreds of millions of people using COVID-19 messenger RNA (mRNA) vaccines will provide much-needed data on non-viral RNA delivery and the immune response, safety, and effectiveness of this type of vaccine. Researchers may use these findings to execute an efficient approach by integrating small interfering RNAs (siRNAs), miRNA mimics, antagomirs, or even genes in the same or comparable lipid nanoparticles used in vaccines for therapeutic applications and gene therapy in the future
Summary
The rapid spread of the novel coronavirus disease 2019 (COVID-19) has hit every corner of the world and has led to drastic changes in the lifestyle of humanity. It was reported that this disease is caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1–3]. COVID-19 was declared a global pandemic by the World Health Organization (WHO) on 30 January 2020 [2]. SARS-CoV-2 is a singlestranded RNA (ssRNA) coronavirus from a subfamily of the Coronaviridae family in the order Nidovirales [4], which has four genera: Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus [5]. The order Nidovirales includes enveloped positive ssRNA.
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