Computational Analysis of Targeting SARS-CoV-2, Viral Entry Proteins ACE2 and TMPRSS2, and Interferon Genes by Host MicroRNAs
Abstract
:1. Introduction
2. Materials and Methods
2.1. SARS-CoV-2 Genomic Analysis
2.2. MiRNA Binding Site Prediction
2.3. MiRNA Expression in Human Tissue and Cell Lines
2.4. Statistical Analysis
3. Results
3.1. Globally Representative SARS-CoV-2 Genomes Demonstrate Minimal Variation in Nucleotide Sequence and Predicted miRNA Binding Sites
3.2. Genomic Regions of SARS-CoV-2 Demonstrate Unique Predicted miRNA Binding Profiles
3.3. Expression of miRNAs in Lungs Predicted to Bind SARS-CoV-2
3.4. Identification and Expression of Predicted miRNAs in SARS-CoV-2-Resistant and -Susceptible Cells
3.5. Identification of Predicted miRNAs to ACE2 and TMPRSS2 in SARS-CoV-2-Resistant and -Susceptible Cells
3.6. Identification of Predicted miRNAs to IFN Genes in SARS-CoV-2-Resistant and -Susceptible Cells
4. Discussion
4.1. MiRNAs Targeting the SARS-CoV-2 Viral Genome
4.2. MiRNAs Targeting Viral Entry Proteins and IFNs
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Location | Wuhan, China (RefSeq) | Washington, USA | Washington, USA | California, USA | Washington, USA | Punjab, Pakistan |
---|---|---|---|---|---|---|
GenBank | MN908947.3 | MT246485.1 | MT345855.1 | MT258382.1 | MT293170.1 | MT262993.1 |
Overall | ||||||
Bases | 29,903 | 29,775 | 29,859 | 29,885 | 29,798 | 29,836 |
Sequence identity a | - | 99.85% b | 99.85% b | 99.87% b | 99.88% b | 99.88% |
5′ UTR | ||||||
Bases | 265 | 137 | 234 | 247 | 151 | 265 |
Sequence identity a | - | 82.5% b | 91.45% b | 99.60 | 92.72% b | 100% |
Mutations | - | - | C→T | C→T | - | - |
S protein | ||||||
Bases | 3822 | 3822 | 3822 | 3822 | 3822 | 3822 |
Sequence identity a | - | 100% | 100% | 99.95% | 100% | 100% |
Mutations | - | - | - | T→W (either T or A); A→G | - | - |
3′ UTR | ||||||
Bases | 229 | 229 | 198 | 229 | 238 | 198 |
Sequence identity a | - | 98.69% | 100% | 93.45% b | 97.38% b | 100% |
Mutations | - | TGAC → AAAA | - | G→R (either G or A); C→M (either C or A) | 9 nt insertion in poly-A tail | - |
Source | ACE2/TMPRSS2 Expression | SARS-CoV-2 Infectivity | |
---|---|---|---|
Huh7 [8,14,32,33] | Liver | High [47] | Moderate |
A549 [8,14,32,33] | Lung | Variable [48] | Low to Moderate |
Calu-3 [8,14,32,34] | Lung | High [49] | High |
Primary human lung fibroblasts [12,13] | Lung | None | Low |
miRNA | Log2-Fold Change | p-value | Favors a |
---|---|---|---|
ORF1ab | |||
miR-139-5p | 0.945 | 0.0305 | Resistant |
miR-664b-3p | 0.733 | 0.0206 | - |
miR-23a-3p | −0.761 | 0.0015 | Resistant |
miR-548d-3p | −0.807 | 0.0517 | - |
miR-15b-5p | −0.812 | 0.0001 | - |
miR-23c | −0.910 | 0.0049 | - |
miR-23b-3p | −0.991 | <0.0001 | Resistant |
miR-374b-3p | −1.069 | 0.0217 | - |
miR-374a-3p | −1.582 | 0.0001 | - |
Nucleocapsid | |||
miR-103a-3p | 0.904 | 0.0005 | - |
miR-107 | 1.040 | 0.0003 | - |
ACE2 | |||
miR-483-3p | 4.460 | <0.0001 | Susceptible |
miR-4463 | 3.048 | <0.0001 | - |
TMPRSS2 | |||
miR-181c-5p | 0.892 | 0.0134 | Resistant |
miR-664b-3p | 0.733 | 0.0206 | - |
miR-182-5p | 0.704 | 0.0134 | Susceptible |
let-7d-5p | 0.464 | 0.0053 | Resistant |
miR-181a-5p | 0.419 | 0.0422 | - |
miR-15b-3p | −0.810 | 0.0008 | - |
miR-494-3p | −0.961 | 0.0326 | Resistant |
IFN-β | |||
miR-450b-5p | −1.441 | 0.0020 | Resistant |
IFN-γ | |||
miR-664b-3p | 0.733 | 0.0206 | - |
miR-26b-5p | −0.475 | 0.0313 | - |
miR-374c-5p | −1.228 | 0.0096 | - |
log2FC | padj | |
---|---|---|
miR-140-3p | −0.007953398 | 0.974817048 |
miR-32-3p | 0.013920456 | 0.974817048 |
miR-374a-5p | 0.020538776 | 0.945449302 |
miR-196b-5p | 0.025080141 | 0.946019864 |
miR-339-5p | 0.029116789 | 0.949059007 |
miR-3158-3p | 0.029234925 | 0.97722196 |
miR-320c | 0.033177006 | 0.970481801 |
miR-423-3p | 0.039739622 | 0.860137595 |
miR-331-5p | 0.04015155 | 0.957965014 |
miR-1180-3p | 0.042520619 | 0.897231993 |
miR-1229-3p | 0.049456491 | 0.979826711 |
miR-6803-3p | 0.069110586 | 0.956513365 |
miR-339-3p | 0.075904611 | 0.883114045 |
miR-4326 | 0.149533463 | 0.815150225 |
miR-16-2-3p | 0.157983774 | 0.530911494 |
miR-6087 | 0.178211797 | 0.945394126 |
miR-25-5p | 0.181172206 | 0.692047229 |
miR-148b-3p | 0.20381122 | 0.369688028 |
miR-126-3p | 0.20432634 | 0.517498738 |
miR-760 | 0.204547203 | 0.876649033 |
miR-200b-5p | 0.206829005 | 0.813533675 |
miR-1307-5p | 0.221466282 | 0.90711043 |
miR-454-3p | 0.226527458 | 0.372951464 |
miR-107 | 0.232189082 | 0.645482953 |
miR-301a-3p | 0.234614774 | 0.88095324 |
miR-200b-3p | 0.241301831 | 0.267692191 |
miR-324-3p | 0.254720466 | 0.852842736 |
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Pierce, J.B.; Simion, V.; Icli, B.; Pérez-Cremades, D.; Cheng, H.S.; Feinberg, M.W. Computational Analysis of Targeting SARS-CoV-2, Viral Entry Proteins ACE2 and TMPRSS2, and Interferon Genes by Host MicroRNAs. Genes 2020, 11, 1354. https://doi.org/10.3390/genes11111354
Pierce JB, Simion V, Icli B, Pérez-Cremades D, Cheng HS, Feinberg MW. Computational Analysis of Targeting SARS-CoV-2, Viral Entry Proteins ACE2 and TMPRSS2, and Interferon Genes by Host MicroRNAs. Genes. 2020; 11(11):1354. https://doi.org/10.3390/genes11111354
Chicago/Turabian StylePierce, Jacob B., Viorel Simion, Basak Icli, Daniel Pérez-Cremades, Henry S. Cheng, and Mark W. Feinberg. 2020. "Computational Analysis of Targeting SARS-CoV-2, Viral Entry Proteins ACE2 and TMPRSS2, and Interferon Genes by Host MicroRNAs" Genes 11, no. 11: 1354. https://doi.org/10.3390/genes11111354