The potential of rapalogs to enhance resilience against SARS-CoV-2 infection and reduce the severity of COVID-19

Bischof, Evelyne; Siow, Richard; Zhavoronkov, Alex; Kaeberlein, Matt

doi:10.1016/s2666-7568(20)30068-4

Cited by 37 publications

(39 citation statements)

References 88 publications

(113 reference statements)

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“…It is possible that Rapamycin, as a co-adjuvant treatment, can improve clinical outcome because it is able to block viral interactions that promotes cell growth, and viral replication. Moreover, Rapamycin can reduce pro-inflammatory cytokines decreasing cell damage in patients with severe COVID-19 ( Bischof et al, 2021 ). The metabolic changes conferred by SARS-CoV-2 infection in renal epithelial cells and lung air-fluid interface (ALI) cultures, showed that SARS-CoV-2 infection reduces the oxidative metabolism of glutamine while maintaining reductive carboxylation, increasing the activity of mTORC1.…”

Section: Discussionmentioning

confidence: 99%

Structural Analysis of SARS-CoV-2 ORF8 Protein: Pathogenic and Therapeutic Implications

et al. 2021

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Current therapeutic strategies and vaccines against SARS-CoV-2 are mainly focused on the Spike protein despite there are other viral proteins with important roles in COVID-19 pathogenicity. For example, ORF8 restructures vesicular trafficking in the host cell, impacts intracellular immunity through the IFN-I signaling, and growth pathways through the mitogen-activated protein kinases (MAPKs). In this mini-review, we analyze the main structural similarities of ORF8 with immunological molecules such as IL−1, contributing to the immunological deregulation observed in COVID-19. We also propose that the blockage of some effector functions of ORF8 with Rapamycin, such as the mTORC1 activation through MAPKs 40 pathway, with Rapamycin, can be a promising approach to reduce COVID-19 mortality.

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Section: Discussionmentioning

confidence: 99%

Structural Analysis of SARS-CoV-2 ORF8 Protein: Pathogenic and Therapeutic Implications

et al. 2021

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“…There are several active clinical trials registered on ClinicalTrials.gov for mTOR inhibitors, such as the rapamycin analog Sirolinus. These clinical trials are based on the proposed effects of rapamycin on restoring T-cell functionality and decrease cytokine storm [94,95], the direct antiviral effect [96], and in aging-related declining of the immune function [97]. Metformin, a medicine commonly used to treat Type 2 Diabetes and a well-known mTOR inhibitor [98], has been demonstrated to reduce COVID-19 mortality [99].…”

Section: Discussionmentioning

confidence: 99%

Increased mTOR signaling, impaired autophagic flux and cell-to-cell viral transmission are hallmarks of SARS-CoV-2 infection

Maktura

Dias

Zambalde

et al. 2021

Preprint

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The COVID-19 disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has two characteristics that distinguish it from other viral infections. It affects more severely people with pre-existing comorbidities and viral load peaks prior to the onset of the symptoms. Investigating factors that could contribute to these characteristics, we found increased mTOR signaling and suppressed genes related to autophagy, lysosome, and vesicle fusion in Vero E6 cells infected with SARS-CoV-2. Transcriptomic data mining of bronchoalveolar epithelial cells from severe COVID-19 patients revealed that COVID-19 severity is associated with increased expression of genes related to mTOR signaling and decreased expression of genes related to au-tophagy, lysosome function, and vesicle fusion. SARS-CoV-2 infection in Vero E6 cells also re-sulted in virus retention inside the cells and trafficking of virus-bearing vesicles between neighboring cells. Our findings support a scenario where SARS-CoV-2 benefits from compromised autophagic flux and inhibited exocytosis in individuals with chronic hyperactivation of mTOR signaling, which might relate to undetectable proliferation and evasion of the immune system.

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“…It is used to prevent organ transplant rejection and treat lung disease [251]. Research has continued on the effectiveness of sirolimus against COVID-19 [252]. Sirolimus' function as an mTOR inhibitor could help to inhibit COVID-19 virus replication [253].…”

Section: Immunosuppressive Compoundsmentioning

confidence: 99%

A Multidisciplinary Approach to Coronavirus Disease (COVID-19)

Ertürk

Şahin

et al. 2021

Molecules

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Since December 2019, humanity has faced an important global threat. Many studies have been published on the origin, structure, and mechanism of action of the SARS-CoV-2 virus and the treatment of its disease. The priority of scientists all over the world has been to direct their time to research this subject. In this review, we highlight chemical studies and therapeutic approaches to overcome COVID-19 with seven different sections. These sections are the structure and mechanism of action of SARS-CoV-2, immunotherapy and vaccine, computer-aided drug design, repurposing therapeutics for COVID-19, synthesis of new molecular structures against COVID-19, food safety/security and functional food components, and potential natural products against COVID-19. In this work, we aimed to screen all the newly synthesized compounds, repurposing chemicals covering antiviral, anti-inflammatory, antibacterial, antiparasitic, anticancer, antipsychotic, and antihistamine compounds against COVID-19. We also highlight computer-aided approaches to develop an anti-COVID-19 molecule. We explain that some phytochemicals and dietary supplements have been identified as antiviral bioproducts, which have almost been successfully tested against COVID-19. In addition, we present immunotherapy types, targets, immunotherapy and inflammation/mutations of the virus, immune response, and vaccine issues.

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The potential of rapalogs to enhance resilience against SARS-CoV-2 infection and reduce the severity of COVID-19

Cited by 37 publications

References 88 publications

Structural Analysis of SARS-CoV-2 ORF8 Protein: Pathogenic and Therapeutic Implications

Structural Analysis of SARS-CoV-2 ORF8 Protein: Pathogenic and Therapeutic Implications

Increased mTOR signaling, impaired autophagic flux and cell-to-cell viral transmission are hallmarks of SARS-CoV-2 infection

A Multidisciplinary Approach to Coronavirus Disease (COVID-19)

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