Small Non-coding RNAs: Do They Encode Answers for Controlling SARS-CoV-2 in the Future?

Abstract

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel coronavirus responsible for the current COVID-19 (coronavirus disease 2019) pandemic, which has hit the world since December 2019. It has spread to about 216 countries worldwide, affecting more than 21.7 million people so far. Although clinical trials of a number of promising antiviral drugs and vaccines against COVID-19 are underway, it is hard to predict how successful these drug-or vaccine-based therapeutics are eventually going to be in combating COVID-19 because most of such therapeutic strategies have failed against human coronaviruses such as SARS-CoV and MERS-CoV (Middle East respiratory syndrome coronavirus) responsible for similar pandemics in the past. In that context, we would like to bring to scientific attention another group of endogenous regulatory molecules, the small non-coding RNAs, especially the microRNAs, which are found to regulate critical cellular pathways in a number of disease conditions, including RNA viral infections. This review will focus on understanding the effect of altered microRNA expression during coronavirus-mediated infections and how it may provide clues for further exploring the pathogenesis of SARS-CoV-2, with a view of developing RNAi-based therapeutics and biomarkers against COVID-19.

Human MicroRNAs Interacting With SARS-CoV-2 RNA Sequences: Computational Analysis and Experimental Target Validation

“…As posttranscriptional regulators, miRNAs play an important role in a broad array of cellular functions, including the complex molecular interplay that is established upon viral infection of host cells ( Umbach and Cullen, 2009 ; Trobaugh and Klimstra, 2017 ). Cellular miRNAs acting on viral RNAs have in fact been identified for human immunodeficiency virus (HIV) ( Ahluwalia et al, 2008 ; Nathans et al, 2009 ), hepatitis C virus ( Murakami et al, 2009 ; Li et al, 2016 ), hepatitis B virus (HBV) ( Zhang et al, 2010 ; Potenza et al, 2011 ), papillomavirus ( Nuovo et al, 2010 ), and many other viruses ( Russo and Potenza, 2011 ; Trobaugh and Klimstra, 2017 ), including RNA viruses causing respiratory pathology such as influenza virus H1N1 and Rhino virus ( Bhattacharyya and Biswas, 2020 ). In the case of HIV and HBV, there is convincing evidence that the identified miRNAs have been co-opted by the virus to fine-tune its replication, keeping it low to escape the immune system and establish a persistent infection ( Huang et al, 2007 ; Mosca et al, 2014 ; Sagnelli et al, 2018 ).…”

Differential expression of miRNAs in a human developing neuronal cell line chronically infected with Zika virus

“…We carried out an homology alignment with modulated miRNAs with the ZIKV genome to determine the viral gene sequences that may be responsible for the molecular pathogenesis of ZIKVinduced neurologic effects in developing fetuses. Our findings will underpin further studies of miRNAs' roles in ZIKV replication and may identify potential candidates for antiviral therapies against ZIKV as well as mechanisms of microcephaly found in ZIKV infected newborns [14,15].…”

“…In a viral infection context, miRNAs have been linked to the interplay between host and pathogen, occupying a major role in pathogenesis. While numerous viral miRNAs from DNA viruses have been identified, characterization of functional RNA virus-encoded miRNAs, and their potential targets as therapeutic agents against numerous viral infections is still ongoing [14,15]. How cellular miRNAs are regulated, and their functions controlled during ZIKV infection, is largely unknown.…”

OverCOVID: an integrative web portal for SARS-CoV-2 bioinformatics resources

“…ncRNAs could be used as a biomarker in the clinical research of COVID-19 [ 30 ], [ 31 ]. The resources that incorporate ncRNA-associated virus–virus, virus–host, host–virus, host–host, RNA-compound interactions, ncRNA–disease associations are listed in this section.…”