A new application of mTOR inhibitor drugs as potential therapeutic agents for COVID-19

Mashayekhi‐Sardoo, Habibeh; Hosseinjani, Hesamoddin

doi:10.1515/jbcpp-2020-0495

Cited by 12 publications

(10 citation statements)

References 50 publications

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“…(Mutvei et al, 2020;Senoo et al, 2019). Finally, we found COVID-19 specific upregulation of the mTOR pathway, and thus its inhibitors may also be used for treatment, since mTOR inhibitors can adjust T cells by induction of autophagy without apoptosis, reduce viral replication, restore T-cell function, and decrease cytokine storm (Mashayekhi-Sardoo and Hosseinjani, 2021).…”

Section: Ifn-i Can Play a Double-edged Role During Viral Infection; While It Restricts Viral Replicationmentioning

confidence: 76%

A single-cell atlas reveals shared and distinct immune responses and metabolism during SARS-CoV-2 and HIV-1 infections

Pan

Cao

Tang

et al. 2022

Preprint

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SARS-CoV-2 and HIV-1 are RNA viruses that have killed millions of people worldwide. Understanding the similarities and differences between these two infections is critical for understanding disease progression and for developing effective vaccines and therapies, particularly for 38 million HIV-1+ individuals who are vulnerable to SARS-CoV-2 co-infection. Here, we utilized single-cell transcriptomics to perform a systematic comparison of 94,442 PBMCs from 7 COVID-19 and 9 HIV-1+ patients in an integrated immune atlas, in which 27 different cell types were identified using an accurate consensus single-cell annotation method. While immune cells in both cohorts show shared inflammation and disrupted mitochondrial function, COVID-19 patients exhibit stronger humoral immunity, broader IFN-I signaling, elevated Rho GTPase and mTOR pathway activities, and downregulated mitophagy. Our results elucidate transcriptional signatures associated with COVID-19 and HIV-1 that may reveal insights into fundamental disease biology and potential therapeutic targets to treat these viral infections.

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Section: Ifn-i Can Play a Double-edged Role During Viral Infection; While It Restricts Viral Replicationmentioning

confidence: 76%

A single-cell atlas reveals shared and distinct immune responses and metabolism during SARS-CoV-2 and HIV-1 infections

Pan

Cao

Tang

et al. 2022

Preprint

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“…Moreover, Rho GTPases have been linked to additional key metabolic controls such as mTOR signaling pathways, which are specifically upregulated in COVID-19 patients ( Senoo et al, 2019 ; Mutvei et al, 2020 ). Targeting mTOR may help to regulate T cells by induction of autophagy without apoptosis, reduce viral replication, restore T-cell function, and decrease cytokine storms ( Mashayekhi-Sardoo and Hosseinjani, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

A single-cell atlas reveals shared and distinct immune responses and metabolic profiles in SARS-CoV-2 and HIV-1 infections

Pan

Cao²,

Tang³

et al. 2023

Front. Genet.

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Introduction: Within the inflammatory immune response to viral infection, the distribution and cell type-specific profiles of immune cell populations and the immune-mediated viral clearance pathways vary according to the specific virus. Uncovering the immunological similarities and differences between viral infections is critical to understanding disease progression and developing effective vaccines and therapies. Insight into COVID-19 disease progression has been bolstered by the integration of single-cell (sc)RNA-seq data from COVID-19 patients with data from related viruses to compare immune responses. Expanding this concept, we propose that a high-resolution, systematic comparison between immune cells from SARS-CoV-2 infection and an inflammatory infectious disease with a different pathophysiology will provide a more comprehensive picture of the viral clearance pathways that underscore immunological and clinical differences between infections.Methods: Using a novel consensus single-cell annotation method, we integrate previously published scRNA-seq data from 111,566 single PBMCs from 7 COVID-19, 10 HIV-1+, and 3 healthy patients into a unified cellular atlas. We compare in detail the phenotypic features and regulatory pathways in the major immune cell clusters.Results: While immune cells in both COVID-19 and HIV-1+ cohorts show shared inflammation and disrupted mitochondrial function, COVID-19 patients exhibit stronger humoral immunity, broader IFN-I signaling, elevated Rho GTPase and mTOR pathway activity, and downregulated mitophagy.Discussion: Our results indicate that differential IFN-I signaling regulates the distinct immune responses in the two diseases, revealing insight into fundamental disease biology and potential therapeutic candidates.

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“…In addition, a number of other mTOR inhibitors, such as metformin (targets AMPK to indirectly inhibit mTOR), everolimus (inhibits mTORC1), RTB101 (inhibits mTORC), sapanisertib (inhibits mTORC1 and mTORC2), and PP‐242 (inhibits mTORC1 and mTORC2), have also been included as candidates for COVID‐19 treatment (reviewed in Refs. 290 and 292 ). To date, NCT04341675 (rapamycin), NCT04461340 (rapamycin), NCT04374903 (rapamycin), and NCT04584710 (RTB101) remain active for recruitment and preparation, with the hope of seeing surprising progress in the future.…”

Section: Intervention Therapymentioning

confidence: 98%

“…Single or combined inhibitors targeting PI3K, Akt, and mTOR may have potential therapeutic effects in the course of SARS‐COV‐2 infection 290,291 . Among them, the most widely studied are mTOR inhibitors 292 …”

Section: Intervention Therapymentioning

confidence: 99%

Inflammatory pathways in COVID‐19: Mechanism and therapeutic interventions

Jiang

Zhao

Zhou

et al. 2022

MedComm

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The 2019 coronavirus disease (COVID‐19) pandemic has become a global crisis. In the immunopathogenesis of COVID‐19, SARS‐CoV‐2 infection induces an excessive inflammatory response in patients, causing an inflammatory cytokine storm in severe cases. Cytokine storm leads to acute respiratory distress syndrome, pulmonary and other multiorgan failure, which is an important cause of COVID‐19 progression and even death. Among them, activation of inflammatory pathways is a major factor in generating cytokine storms and causing dysregulated immune responses, which is closely related to the severity of viral infection. Therefore, elucidation of the inflammatory signaling pathway of SARS‐CoV‐2 is important in providing otential therapeutic targets and treatment strategies against COVID‐19. Here, we discuss the major inflammatory pathways in the pathogenesis of COVID‐19, including induction, function, and downstream signaling, as well as existing and potential interventions targeting these cytokines or related signaling pathways. We believe that a comprehensive understanding of the regulatory pathways of COVID‐19 immune dysregulation and inflammation will help develop better clinical therapy strategies to effectively control inflammatory diseases, such as COVID‐19.

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A new application of mTOR inhibitor drugs as potential therapeutic agents for COVID-19

Cited by 12 publications

References 50 publications

A single-cell atlas reveals shared and distinct immune responses and metabolism during SARS-CoV-2 and HIV-1 infections

A single-cell atlas reveals shared and distinct immune responses and metabolism during SARS-CoV-2 and HIV-1 infections

A single-cell atlas reveals shared and distinct immune responses and metabolic profiles in SARS-CoV-2 and HIV-1 infections

Inflammatory pathways in COVID‐19: Mechanism and therapeutic interventions

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