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Dataset of mutational analysis, miRNAs targeting SARS-CoV-2 genes and host gene expression in SARS-CoV and SARS-CoV-2 infections.

ABSTRACT: The identification of host-miRNAs targeting mutated virus genes is crucial to understand the miRNA mediated host-defense mechanism in virus infections. To understand the mechanism in COVID-19 infections, we collected genome sequences of SARS-CoV-2 with its metadata from the GISAID database (submitted till April 2020) and identified mutational changes in the sequences. The dataset consists of genes with mutation event count and entropy scores. We predicted host-miRNAs targeting the genes in the genomes and compared it with that in related viral species. We have identified 2284 miRNAs targeting MERS genomes, 2074 miRNAs targeting SARS genomes, and 1599 miRNAs targeting SARS-CoV-2 genomes, identified using the miRNA target prediction software miRanda. The host miRNAs targeting SARS-CoV-2 genes were further validated to be anti-viral miRNAs and their role in respiratory diseases through a literature survey, which helped in the identification of 42 conserved antiviral miRNAs. The data could be used to validate the anti-viral role of the predicted miRNAs and design miRNA-based therapeutics against SARS-CoV-2.

SUBMITTER: Sardar R

PROVIDER: S-EPMC7442128 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The coronavirus disease 2019, COVID-19, is a complex disease with a wide range of symptoms from asymptomatic infections to severe acute respiratory syndrome with lethal outcome. Individual factors such as age, sex, and comorbidities increase the risk for severe infections, but other aspects, such as genetic variations, are also likely to affect the susceptibility to SARS-CoV-2 infection and disease severity. Here, we used a human 3D lung cell model based on primary cells derived from multiple donors to identity host factors that regulate SARS-CoV-2 infection. With a transcriptomics-based approach, we found that less susceptible donors show a higher expression level of serine protease inhibitors SERPINA1, SERPINE1, and SERPINE2, identifying variation in cellular serpin levels as restricting host factors for SARS-CoV-2 infection. We pinpoint their antiviral mechanism of action to inhibition of the cellular serine protease, TMPRSS2, thereby preventing cleavage of the viral spike protein and TMPRSS2-mediated entry into the target cells. By means of single-cell RNA sequencing, we further locate the expression of the individual serpins to basal, ciliated, club, and goblet cells. Our results add to the importance of genetic variations as determinants for SARS-CoV-2 susceptibility and suggest that genetic deficiencies of cellular serpins might represent risk factors for severe COVID-19. Our study further highlights TMPRSS2 as a promising target for antiviral intervention and opens the door for the usage of locally administered serpins as a treatment against COVID-19. IMPORTANCE Identification of host factors affecting individual SARS-CoV-2 susceptibility will provide a better understanding of the large variations in disease severity and will identify potential factors that can be used, or targeted, in antiviral drug development. With the use of an advanced lung cell model established from several human donors, we identified cellular protease inhibitors, serpins, as host factors that restrict SARS-CoV-2 infection. The antiviral mechanism was found to be mediated by the inhibition of a serine protease, TMPRSS2, which results in a blockage of viral entry into target cells. Potential treatments with these serpins would not only reduce the overall viral burden in the patients, but also block the infection at an early time point, reducing the risk for the hyperactive immune response common in patients with severe COVID-19.

Dataset Information

Dataset of mutational analysis, miRNAs targeting SARS-CoV-2 genes and host gene expression in SARS-CoV and SARS-CoV-2 infections.

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