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Understanding the epigenetic mechanisms in SARS CoV-2 infection and potential therapeutic approaches.

ABSTRACT: COVID-19 pandemic caused by the Severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) has inflicted a global health challenge. Although the overwhelming escalation of mortality seen during the initial phase of the pandemic has reduced, emerging variants of SARS-CoV-2 continue to impact communities worldwide. Several studies have highlighted the association of gene specific epigenetic modifications in host cells with the pathogenesis and severity of the disease. Therefore, alongside the investigations into the virology and pathogenesis of SARS-CoV-2 infection, understanding the epigenetic mechanisms related to the disease is crucial for the rational design of effective targeted therapies. Here, we discuss the interaction of SARS-CoV-2 with the various epigenetic regulators and their subsequent contribution to the risk of disease severity and dysfunctional immune responses. Finally, we also highlight the use of epigenetically targeted drugs for the potential therapeutic interventions capable of eliminating viral infection and/or build effective immunity against it.

SUBMITTER: Bhat S

PROVIDER: S-EPMC9236910 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Understanding the epigenetic mechanisms in SARS CoV-2 infection and potential therapeutic approaches.

Bhat Swati S Rishi Praveen P Chadha Vijayta D VD

Virus research 20220628

COVID-19 pandemic caused by the Severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) has inflicted a global health challenge. Although the overwhelming escalation of mortality seen during the initial phase of the pandemic has reduced, emerging variants of SARS-CoV-2 continue to impact communities worldwide. Several studies have highlighted the association of gene specific epigenetic modifications in host cells with the pathogenesis and severity of the disease. Therefore, alongside the i ...[more]

PMID: 35777502

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Project description:BackgroundThe ongoing COVID-19 outbreak has caused devastating mortality and posed a significant threat to public health worldwide. Despite the severity of this illness and 2.3 million worldwide deaths, the disease mechanism is mostly unknown. Previous studies that characterized differential gene expression due to SARS-CoV-2 infection lacked robust validation. Although vaccines are now available, effective treatment options are still out of reach.ResultsTo characterize the transcriptional activity of SARS-CoV-2 infection, a gene signature consisting of 25 genes was generated using a publicly available RNA-Sequencing (RNA-Seq) dataset of cultured cells infected with SARS-CoV-2. The signature estimated infection level accurately in bronchoalveolar lavage fluid (BALF) cells and peripheral blood mononuclear cells (PBMCs) from healthy and infected patients (mean 0.001 vs. 0.958; P < 0.0001). These signature genes were investigated in their ability to distinguish the severity of SARS-CoV-2 infection in a single-cell RNA-Sequencing dataset. TNFAIP3, PPP1R15A, NFKBIA, and IFIT2 had shown bimodal gene expression in various immune cells from severely infected patients compared to healthy or moderate infection cases. Finally, this signature was assessed using the publicly available ConnectivityMap database to identify potential disease mechanisms and drug repurposing candidates. Pharmacological classes of tricyclic antidepressants, SRC-inhibitors, HDAC inhibitors, MEK inhibitors, and drugs such as atorvastatin, ibuprofen, and ketoconazole showed strong negative associations (connectivity score < - 90), highlighting the need for further evaluation of these candidates for their efficacy in treating SARS-CoV-2 infection.ConclusionsThus, using the 25-gene SARS-CoV-2 infection signature, the SARS-CoV-2 infection status was captured in BALF cells, PBMCs and postmortem lung biopsies. In addition, candidate SARS-CoV-2 therapies with known safety profiles were identified. The signature genes could potentially also be used to characterize the COVID-19 disease severity in patients' expression profiles of BALF cells.

Dataset Information

Understanding the epigenetic mechanisms in SARS CoV-2 infection and potential therapeutic approaches.

Publications

Understanding the epigenetic mechanisms in SARS CoV-2 infection and potential therapeutic approaches.

Similar Datasets

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