**Background:** SARS-CoV-2 genome is composed of a positive-sense single-stranded 30Kb long RNA that structurally resembles eukaryotic mRNAs. The sequence comprises 12 putative coding regions flanked by a 5’-UTR methylated cap and a 3’-UTR with a poly-A tail (Lu et al., 2020).
MicroRNAs are short non-coding RNA sequences that bind to target messenger RNAs (mRNAs), causing their cleavage or translational block to modulate a range of fundamental cellular processes. MicroRNA-mediated RNA interference provides a layer of post-transcriptional gene regulation employed by virus and host to enhance or inhibit viral infection (Trobaugh & Klimstra, 2017; Bruscella et al., 2017) with potential therapeutic applications currently under clinical trial (Chakraborty et al., 2020).
**Hypothesis:** resemblance of SARS-CoV-2 genome to mRNAs suggests it may contain binding sites for microRNAs as observed in most mammal genes
**Methods:** *in silico* screening to predict endogenous human microRNAs targeting the 3’-UTR of SARS-CoV-2 combined with validations using gene reporter assays.
**Results:** results from the computational analyses allowed us to identify 10 potential candidates. 3 of them, together with hsa-miR-138-5p, were validated by gene reporter assays. Available information indicates that two of these microRNAs, namely hsa-miR-3941 and hsa-miR-138-5p, combine effective targeting of SARS-CoV-2 genome with complementary antiviral or tissue repairing effects in the host cells that make them potential candidates for therapeutic treatment of COVID-19.
**The team** is composed of molecular biologists Rodrigo M. Maza, M Asunción de la Barreda Manso, Manuel Nieto-Diaz, David Regiada, Altea Soto, and Teresa Muñoz-Galdeano from the Research Unit of the Hospital Nacional de Parapléjicos.
**Funding:** research was supported by 750€ from the Fondo Solidario COVID-19 of Globalcaja Foundation and a 8 months fellowship for MABM from the Fundación del Hospital Nacional de Parapléjicos para la Investigación y la Integración (FUHNPAIIN), and co-financed by the European Union (FEDER) “A way to make Europe”.
The authors declare **no conflicts of interest**.
