In silico analysis reveals hypoxia-induced miR-210-3p specifically targets SARS-CoV-2 RNA

Abstract

Human coronaviruses (HCoVs) until the emergence of SARS in 2003 were associated with mild cold and upper respiratory tract infections. The ongoing pandemic caused by SARS-CoV-2 has enhanced the potential for infection and transmission as compared to other known members of this family. MicroRNAs (miRNA) are 21-25 nucleotides long non-coding RNA that bind to 3' UTR of genes and regulate almost every aspect of cellular function. Several human miRNAs have been known to target viral genomes, mostly to downregulate their expression and sometimes to upregulate also. In some cases, host miRNAs could be sequestered by the viral genome to create a condition for favourable virus existence. The ongoing SARS CoV-2 pandemic is unique based on its transmissibility and severity and we hypothesised that there could be a unique mechanism for its pathogenesis. In this study, we exploited in silico approach to identify human respiratory system-specific miRNAs targeting the viral genome of three highly pathogenic HCoVs (SARS-CoV-2 Wuhan strain, SARS-CoV, and MERS-CoV) and three low pathogenic HCoVs (OC43, NL63, and HKU1). We identified ten common microRNAs that target all HCoVs studied here. In addition, we identified unique miRNAs which targeted specifically one particular HCoV. miR-210-3p was the single unique lung-specific miRNA, which was found to target the NSP3, NSP4, and NSP13 genes of SARS-CoV-2. Further miR-210-NSP3, miR-210-NSP4, and miR-210-NSP13 SARS-CoV-2 duplexes were docked with the hAGO2 protein (PDB ID 4F3T) which showed Z-score values of −1.9, −1.7, and −1.6, respectively. The role of miR-210-3p as master hypoxia regulator and inflammation regulation may be important for SARS-CoV-2 pathogenesis. Overall, this analysis advocates that miR-210-3p be investigated experimentally in SARS-CoV-2 infection.

Communicated by Ramaswamy H. Sarma

Keywords:

• Human coronavirus
• SARS-CoV-2
• hsa-miR-210-3p
• hypoxia
• hybridization energy
• STRING analysis
• HADDOCK
• Z-score
• human AGO2 protein

Author contribution

Mirza Sarwar Baig- Conceived and designed research, employed following software and servers in this study-miRDB, Tarbase, miRTarbase, miRTargetLink, miRPathDB, miRSel, STRING DB, DAVID 6.8, IntaRNA, RNAstructureWeb server, RNACOMPOSER, 3dRNA version 2.0 webserver, HADDOCK2.4 biomolecular docking webserver, miR2Disease, PolymiRTS database; analyzed the data, and wrote the manuscript. Deepanshu- Performed MD simulation. Prem Prakash—Performed MD simulation and analysis. Pravej Alam- Performed STarMir analysis for RNA accessibility. Anuja Krishnan- Conceptualised, designed experiments, supervised, analyzed and finalized the manuscript.

Additional information

Funding

The research is supported by the Indian Council of Medical Research (ICMR), New Delhi (VIR/Fellowship/40/2019/ECD-1) to whom M.S.B duly acknowledges. AK acknowledges funding from Department of Biotechnology, (BT/PR40963/COT/142/12/2020) and CCRUM (F.No.3-60/2019-CCRUM/Tech). PP is supported by Science and Engineering Research Board, Department of Science and Technology (ECR/2017/000235 and EEQ/2020/000299), Indian Council of Medical Research (ICMR) (P-12)ITR/Adhoc/18/2020), Department of Biotechnology, (BT/RLF/Re-Entry/24/2015) and the University Grants Commission, Faculty Recharge Programme No.F.4-5(67-FRP) (Cycle-IV)/2017(BSR).