Cellular miR-150-5p may have a crucial role to play in the biology of SARS-CoV-2 infection by regulating nsp10 gene

Abstract

The role for circulating miRNAs as biomarkers of the COVID-19 disease remains uncertain. We analysed the circulating miRNA profile in twelve COVID-19 patients with moderate-severe disease. This analysis was conducted by performing next generation sequencing (NGS) followed by real-time polymerase chain reaction (RT-qPCR). Compared with healthy controls, we detected significant changes in the circulating miRNA profile of COVID-19 patients. The miRNAs that were significantly altered in all the COVID-19 patients were miR-150-5p, miR-375, miR-122-5p, miR-494-3p, miR-3197, miR-4690-5p, miR-1915-3p, and miR-3652. Infection assays performed using miRNA mimics in HEK-293 T cells determined miR-150-5p to have a crucial role in SARS-CoV-2 infection and this was based on the following data: (i) miR-150-5p mimic lowered in vitro SARS-CoV-2 infection; (ii) miR-150-5p inhibitor reversed the effects of miR-150-5p mimic on SARS-CoV-2 infection of cells; and (iii) a novel miRNA recognition element (MRE) was identified in the coding strand of SARS-CoV-2 nsp10 , the expression of which could be inhibited by miR-150-5p mimic. Our findings identified crucial miRNA footprints in COVID-19 patients with moderate-severe disease. A combination of co-transfection and Western blotting experiments also determined the ability of miR-150-5p to inhibit SARS-CoV-2 infection via directly interacting with MRE in the coding strand of nsp10 . Our investigation showed that a sharp decline in the miR-150-5p plasma levels in COVID-19 patients may support enhanced SARS-CoV-2 infection. Furthermore, this study provides insight into one possible mechanism by which COVID-19-induced changes to miR-150-5p levels may promote SARS-CoV-2 infection via modulating nsp10 expression.

Inducible miR-150 Inhibits Porcine Reproductive and Respiratory Syndrome Virus Replication by Targeting Viral Genome and Suppressor of Cytokine Signaling 1

“…Moreover, miR-150, which is highly expressed in in patients with severe A/H1N1 disease, is also shown to inhibit H1N1 replication through targeting the PB2 gene [ 66 , 67 ]. miR-150 also targets SARS-CoV-2 nsp10 to suppress its infection [ 68 ]. As a virus inducible regulator, miR-150 seems to have a broad-spectrum antiviral ability [ 69 ].…”

Dysregulated miRNAs network in the critical COVID-19: An important clue for uncontrolled immunothrombosis/thromboinflammation

“…2 c-F). In this regard, the deregulated expression patterns of miR-340, miR-375 (reduced), and miR-27a/b (elevated) were found in patients with the COVID-19 [170] , [196] , [198] , [222] . Considerably, all of the miRNAs affecting the other pathways/events ( e.g ., neutrophils/monocytes activities, NETosis, ECs dysfunction, the complement activation, and hypoxia/hypoxemia) can indirectly affect the fibrinolysis process and endogenous anticoagulants ( Fig.…”

“…2 c-E). In this regard, the non-optimal circular expression levels of some of these miRNAs such as miR-150, miR-218, miR-494-3p, miR-20b (reduced), and miR-155 (elevated) have been observed in patients with the COVID-19 [173] , [193] , [196] , [199] , [222] . Furthermore, the indirect effects of the miRNAs on the other pathways/events ( e.g ., neutrophils/monocytes activities, NETosis, and hypoxia/hypoxemia) ( Fig.…”

Preclinical efficacy and safety of novel SNAT against SARS-CoV-2 using a hamster model

“…All work pertaining to the use of SARS-CoV-2 were performed in BSL-3 laboratory. SARS-CoV-2 (isolate USA-WA1/2020) purchased from bei RESOURCES (Manassas, VA) was propagated in Vero cells as per standard procedures [ 19 ]. SARS-CoV-2 virus was propagated in Vero cells, purified and concentrated using 10–30% sucrose gradient in an ultracentrifuge (Beckman L8-55), and the yield titrated as per standard protocols [ 20 ].…”