Simultaneous Treatment of COVID-19 With Serine Protease Inhibitor Camostat and/or Cathepsin L Inhibitor?

Bittmann, Stefan; Weissenstein, Anne; Villalon, Gloria; Moschüring-Alieva, Elena; Luchter, Elisabeth

doi:10.14740/jocmr4161

Cited by 27 publications

(30 citation statements)

References 11 publications

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“…Further studies will be required, particularly in SARS-CoV-2 infection models, to further define the contribution of each viral entry pathway to COVID-19 pathology. Notably, it has recently been proposed that SARS-CoV-2 entry blockade may require inhibition of both the cell surface and endocytic pathways [ 57 ].…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 tropism, entry, replication, and propagation: Considerations for drug discovery and development

Murgolo

Therien

Howell³

et al. 2021

PLoS Pathog

192

169

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Since the initial report of the novel Coronavirus Disease 2019 (COVID-19) emanating from Wuhan, China, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread globally. While the effects of SARS-CoV-2 infection are not completely understood, there appears to be a wide spectrum of disease ranging from mild symptoms to severe respiratory distress, hospitalization, and mortality. There are no Food and Drug Administration (FDA)-approved treatments for COVID-19 aside from remdesivir; early efforts to identify efficacious therapeutics for COVID-19 have mainly focused on drug repurposing screens to identify compounds with antiviral activity against SARS-CoV-2 in cellular infection systems. These screens have yielded intriguing hits, but the use of nonhuman immortalized cell lines derived from non-pulmonary or gastrointestinal origins poses any number of questions in predicting the physiological and pathological relevance of these potential interventions. While our knowledge of this novel virus continues to evolve, our current understanding of the key molecular and cellular interactions involved in SARS-CoV-2 infection is discussed in order to provide a framework for developing the most appropriate in vitro toolbox to support current and future drug discovery efforts.

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Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 tropism, entry, replication, and propagation: Considerations for drug discovery and development

Murgolo

Therien

Howell³

et al. 2021

PLoS Pathog

192

169

View full text Add to dashboard Cite

show abstract

“…This module included the NUPR1 stress response gene, and CSTB which is an inhibitor of cathepsins like CTSL and CTSB that are involved in COVID-19 viral entry. ( Bittmann et al, 2020 ) Module 4 was significantly underexpressed in BAL of severe patients versus healthy controls.…”

Section: Resultsmentioning

confidence: 96%

“…( Santofimia-Castaño et al, 2018 ) Lastly, our observation that CTSL, a protein crucial for COVID-19 viral entry is upregulated across multiple cell types in severe patients provides a potential initial mechanism for the induction of the NEAT1 and MALAT1 mediated inflammatory state through increased efficiency of viral entry. ( Bittmann et al, 2020 )…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNAs (lncRNAs) NEAT1 and MALAT1 are differentially expressed in severe COVID-19 patients: An integrated single cell analysis

Kai

Wang

Vagts

et al. 2021

Preprint

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Hyperactive and damaging inflammation is a hallmark of severe rather than mild COVID-19 syndrome. To uncover key inflammatory differentiators between severe and mild COVID-19 disease, we applied an unbiased single-cell transcriptomic analysis. We integrated a bronchoalveolar lavage (BAL) dataset with a peripheral blood mononuclear cell dataset (PBMC) and analyzed the combined cell population, focusing on genes associated with disease severity. Distinct cell populations were detected in both BAL and PBMC where the immunomodulatory long non-coding RNAs (lncRNAs) NEAT1 and MALAT1 were highly differentially expressed between mild and severe patients. The detection of other severity associated genes involved in cellular stress response and apoptosis regulation suggests that the pro-inflammatory functions of these lncRNAs may foster cell stress and damage. The lncRNAs NEAT1 and MALAT1 are potential components of immune dysregulation in COVID-19 that may provide targets for severity related diagnostic measures or therapy.

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“…The serine protease TMPRSS2 is overexpressed in alveolar cells and enhances the binding between ACE2 and the S protein of SARS-CoV-2, mediating the endosomal and lysosomal entrance and processing of viral particles through host-viral membrane fusion ( Sungnak et al, 2020 ). It has been clinically proven that TMPRSS2 inhibitors can block the entry of SARS-CoV-2 into host cells by inhibiting the acidic protease activity ( Bittmann et al, 2020 ). This mechanism of action has drawn the attention of drug development designers targeting this process with chloroquine and the less toxic hydroxychloroquine ( Blaess et al, 2020 , Colson et al, 2020 ).…”

Section: Current Anti-covid-19 Medications Under Investigation Relatementioning

confidence: 99%

Current approaches used in treating COVID-19 from a molecular mechanisms and immune response perspective

Alnefaie

Albogami

2020

Saudi Pharmaceutical Journal

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Coronavirus disease 2019 (COVID-19), which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared by the World Health Organization (WHO) as a global pandemic on March 11, 2020. SARS-CoV-2 targets the respiratory system, resulting in symptoms such as fever, headache, dry cough, dyspnea, and dizziness. These symptoms vary from person to person, ranging from mild to hypoxia with acute respiratory distress syndrome (ARDS) and sometimes death. Although not confirmed, phylogenetic analysis suggests that SARS-CoV-2 may have originated from bats; the intermediary facilitating its transfer from bats to humans is unknown. Owing to the rapid spread of infection and high number of deaths caused by SARS-CoV-2, most countries have enacted strict curfews and the practice of social distancing while awaiting the availability of effective U.S. Food and Drug Administration (FDA)-approved medications and/or vaccines. This review offers an overview of the various types of coronaviruses (CoVs), their targeted hosts and cellular receptors, a timeline of their emergence, and the roles of key elements of the immune system in fighting pathogen attacks, while focusing on SARS-CoV-2 and its genomic structure and pathogenesis. Furthermore, we review drugs targeting COVID-19 that are under investigation and in clinical trials, in addition to progress using mesenchymal stem cells to treat COVID-19. We conclude by reviewing the latest updates on COVID-19 vaccine development. Understanding the molecular mechanisms of how SARS-CoV-2 interacts with host cells and stimulates the immune response is extremely important, especially as scientists look for new strategies to guide their development of specific COVID-19 therapies and vaccines.

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Simultaneous Treatment of COVID-19 With Serine Protease Inhibitor Camostat and/or Cathepsin L Inhibitor?

Cited by 27 publications

References 11 publications

SARS-CoV-2 tropism, entry, replication, and propagation: Considerations for drug discovery and development

SARS-CoV-2 tropism, entry, replication, and propagation: Considerations for drug discovery and development

Long non-coding RNAs (lncRNAs) NEAT1 and MALAT1 are differentially expressed in severe COVID-19 patients: An integrated single cell analysis

Current approaches used in treating COVID-19 from a molecular mechanisms and immune response perspective

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