Remdesivir Treatment alters Circulating MicroRNA Profile in Coronavirus Disease 2019 (COVID-19) Patients

Abstract

Abstract Coronavirus disease 2019 (COVID-19), a serious infectious disease caused by the newly discovered Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), represents a significant global health crisis nowadays. Although no specific antiviral drug has been proven to be fully effective against COVID-19, Remdesivir (GS-5734), a nucleoside analogue prodrug, showed beneficial effects upon treating severe hospitalized COVID-19 cases. The molecular mechanism underlying this beneficial therapeutic effect is still vague. In this study, we assessed the effect of Remdesivir treatment on the signature of circulating miRNAs in the plasma of COVID-19 patients. MiRCURY LNA miRNome qPCR Panels were used to characterize the miRNA signature. Individual quantitative real-time RT-PCR (qRT-PCR) was performed to confirm the outcome of miRCURY LNA miRNome qPCR Panels. Our results revealed that Remdesivir can restore the expression of a panel of miRNAs being upregulated in COVID-19 patients into levels comparable to those exhibited by healthy donors. Bioinformatics analysis revealed that these miRNAs are involved in diverse biological processes such as Transforming growth factor beta (TGF-β) signalling pathway, Hippo signaling, P53 signalling and Rap1 signaling pathway. On the other hand, 3 miRNAs (hsa-miR-7-5p, hsa-miR-10b-5p, hsa-miR-130b-3p) were upregulated in patients only following Remdesivir treatment or in naturally remitted patients. These upregulated miRNAs could serve as biomarkers of COVID-19 remission. The output of this study highlights that Remedisivir therapeutic potential involves miRNA-regulated molecular mechanisms.