Overall, by making the host cell more amenable to viral infection or through direct interactions with the virus, miRNAs serve an important role in regulating viral infections and can be explored for developing novel antiviral therapeutics. Evidently, miRNAs can regulate a wide variety of viral infections, including respiratory infections such as HCoVs. sequences, to identify potential binding sites for miRNAs hypothesized to play a role in SARS-CoV-2 infection. miRNAs that target angiotensin-converting enzyme 2 (ACE2), the receptor used by SARS-CoV-2 and SARS-CoV for host cell entry, were also predicted. Several relevant miRNAs were identified, and their potential roles in regulating SARS-CoV-2 infections were further assessed. Current treatment options for SARS-CoV-2 are limited and have not generated sufficient evidence on safety and efficacy for treating COVID-19. Therefore, Mouse monoclonal to IGF2BP3 by investigating the interactions between miRNAs and SARS-CoV-2, miRNA-based antiviral therapies, including miRNA mimics and inhibitors, may be developed as an alternative strategy to fight COVID-19. Key Points MicroRNAs (miRNAs) regulate hostCvirus interactions through direct interactions with the viral genome or by altering the hosts cellular microenvironment.RNA and miRNA-based antiviral therapeutics are evolving BAY 61-3606 and represent a promising therapeutic option. In this study, we utilized available computational and miRNA target prediction tools and databases to identify key miRNAs that may have a role in modulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Open in a separate window SARS-CoV-2 and the BAY 61-3606 COVID-19 Pandemic The newly emerged human coronavirus (HCoV), named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the etiologic agent responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic and has infected ~ 100 million people and caused ~ 2 million deaths worldwide at the time of submission [1, 2]. While some COVID-19 patients remain asymptomatic or present with mild flu-like symptoms, others develop severe respiratory distress, cardiac complications, renal failure, septic shock, and other long-term health complications [3]. Despite global efforts to control the spread of the virus, many countries are now facing a second rise in COVID-19 cases with uncontrolled SARS-CoV-2 spreading in populations, leading to a need for effective antiviral treatments and vaccine developments [2]. Coronaviruses are enveloped single-stranded RNA viruses and are divided into four genera, being the only genera infecting humans [4, 5]. HCoVs originate from animal hosts, and SARS-CoV-2 is now the third highly pathogenic to cross the species barrier, along with the previously identified severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) [4C7]. SARS-CoV-2 presents high sequence homology with SARS-CoV (around 80%) and similar cell tropism in the lower respiratory tract, infecting pulmonary epithelial alveolar type II cells [8, 9]. Notably, both SARS-CoV-2 and SARS-CoV use the angiotensin-converting enzyme 2 (ACE2) as their functional receptor and gain access to the cell cytoplasm after the specific interaction of their Spike glycoprotein with ACE2 and subsequent viral membraneChost membrane fusion in the endosomal compartment [10]. In addition to the cell receptor, several membrane proteins have been shown to facilitate SARS-CoV-2 cell entry such as the transmembrane protease serine 2 (TMPRSS2), the lysosomal cathepsins B/L, and neuropilin-1 [10C12]. Moreover, SARS-CoV-2 acquired a furin cleavage site between the S1 and S2 subunits of its Spike protein, leading to the proteolytic pre-activation of the glycoprotein, a feature necessary for viral entry, and could explain the high pathogenicity of the virus given the ubiquitous expression of the furin protease combined with the large distribution of ACE2 outside of the lungs [10]. Following entry, the viral genome is released into the cell cytoplasm to start the replicative cycle. SARS-CoV-2 possesses a large single-stranded, positive-sense RNA genome (29.9 kb), organized in 11 open reading frames (ORF) surrounded by a 5 and 3 untranslated region (UTR) and coding for 16 non-structural, four structural, and six accessory proteins [13, 14]. The viral replication machinery comprises several viral BAY 61-3606 proteins (replicase, helicase, RNA-dependent RNA polymerase complex, and endoribonuclease) that are synthesized as large polyproteins called PP1a and PP1ab, encoded by ORF1a and ORF1b, and cleaved into individual proteins by the viral proteases PLpro and 3CLpro [15]. Current therapeutic strategies to treat COVID-19 patients rely on the management of the diseases most severe symptoms and on the administration of the antiviral drug remdesivir in the most severe BAY 61-3606 cases [16]. Among the current efforts to fight COVID-19, some notable approaches include finding entry and replication inhibitors and repurposing existing antiviral drugs [17]. To date, over 2000 COVID-19 clinical trials have been registered worldwide, ranging.