CPZ
carboxypeptidase Z
Gene Context Sentence
Table 2. Analysis of context sentence of CPZ gene in 4 abstracts.
| PMID | Gene Context Sentence |
|---|---|
| 32387014 | Chlorpromazine (CPZ) is a phenothiazine derivative widely used in clinical routine in the treatment of acute and chronic psychoses. […] In addition, to its antipsychotic effects, several in vitro studies have also demonstrated a CPZ antiviral activity via the inhibition of clathrin-mediated endocytosis. […] Recently, independent studies revealed that CPZ is an anti-MERS-CoV and an anti-SARS-CoV-1 drug. […] In comparison to other antiviral drugs, the main advantages of CPZ lie in its biodistribution: (i) preclinical and clinical studies have reported a high CPZ concentration in the lungs (20-200 times higher than in plasma), which is critical because of the respiratory tropism of SARS-CoV-2; (ii) CPZ is highly concentrated in saliva (30-100 times higher than in plasma) and could therefore reduce the contagiousness of COVID-19; (iii) CPZ can cross the blood-brain barrier and could therefore prevent the neurological forms of COVID-19. […] Our hypothesis is that CPZ could decrease the unfavorable evolution of COVID-19 infection in oxygen-requiring patients without the need for intensive care, but also reduce the contagiousness of SARS-CoV-2. […] Efficacy of CPZ will be assessed according to clinical, biological and radiological criteria. […] The main objective is to demonstrate a shorter time to response (TTR) to treatment in the CPZ+standard-of-care (CPZ+SOC) group, compared to the SOC group. […] The secondary objectives are to demonstrate in the CPZ+SOC group, compared to the SOC group: (A) superior clinical improvement; (B) a greater decrease in the biological markers of viral attack by SARS-CoV-2 (PCR, viral load); (C) a greater decrease in inflammatory markers (e.g. […] CRP and lymphopenia); (D) a greater decrease in parenchymal involvement (chest CT) on the seventh day post-randomization; (E) to define the optimal dosage of CPZ and its tolerance; (F) to evaluate the biological parameters of response to treatment, in particular the involvement of inflammatory cytokines. […] This repositioning of CPZ as an anti-SARS-CoV-2 drug offers an alternative and rapid strategy to alleviate the virus propagation and the infection severity and lethality. […] This CPZ repositioning strategy also avoids numerous developmental and experimental steps and can save precious time to rapidly establish an anti-COVID-19 therapy with well-known, limited and easy to manage side effects. […] Indeed, CPZ is an FDA-approved drug with an excellent tolerance profile, prescribed for around 70 years in psychiatry but also in clinical routine in nausea and vomiting of pregnancy, in advanced cancer and also to treat headaches in various neurological conditions. […] The broad spectrum of CPZ treatment - including antipsychotic, anxiolytic, antiemetic, antiviral, immunomodulatory effects along with inhibition of clathrin-mediated endocytosis and modulation of blood-brain barrier - is in line with the historical French commercial name for CPZ, i.e. […] The discovery of those CPZ properties, as for many other molecules in psychiatry, is both the result of serendipity and careful clinical observations. |
| 32425222 | Chlorpromazine (CPZ), a phenothiazine derivative, is also known for its antiviral activity via the inhibition of clathrin-mediated endocytosis. […] Recent in vitro studies have reported that CPZ exhibits anti-MERS-CoV and anti-SARS-CoV-1 activity. […] In this context, the ReCoVery study aims to repurpose CPZ, a molecule with an excellent tolerance profile and a very high biodistribution in the saliva, lungs and brain. […] We hypothesize that CPZ could reduce the unfavorable course of COVID-19 infection among patients requiring respiratory support without the need for ICU care, and that it could also reduce the contagiousness of SARS-CoV-2. […] CPZ + standard treatment). […] This repurposing of CPZ for its anti-SARS-CoV-2 activity could offer an alternative, rapid strategy to alleviate infection severity. |
| 33387629 | Chlorpromazine (CPZ), an antipsychotic from the phenothiazine group, is known to inhibit clathrin-mediated endocytosis and has antiviral activity against severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) and Middle East respiratory syndrome coronavirus. […] The aim of this in-vitro study was to test CPZ against SARS-CoV-2 in monkey and human cells. […] Monkey VeroE6 cells and human alveolar basal epithelial A549-ACE2 cells were infected with SARS-CoV-2 in the presence of various concentrations of CPZ. […] Cell viability was assessed in non-infected cells. of 23.1 µM and SI of 2.04. values measured in vitro may translate to CPZ dosages used in routine clinical practice because of the high biodistribution of CPZ in lungs and saliva. […] Also, the distribution of CPZ in brain could be of interest for treating or preventing neurological and psychiatric forms of COVID-19. […] These preclinical findings support clinical investigation of the repurposing of CPZ, a drug with mild side effects, in the treatment of patients with COVID-19. |
| 33390948 | This review aims to 1) inform health care professionals and scientists about the history of CPZ use in psychiatry and its potential anti- SARS-CoV-2 activities 2) inform psychiatrists about its potential anti-SARS-CoV-2 activities, and 3) propose a research protocol for investigating the use of CPZ in the treatment of COVID-19 during the potential second wave. […] The history of CPZ’s discovery and development is described in addition to the review of literature from published studies within the discipline of virology related to CPZ. […] The possible mechanism of action of CPZ is related to virus cell entry via clathrin-mediated endocytosis. […] Therefore, CPZ could be useful to treat COVID-19 patients provided that its efficacy is evaluated in adequate and well-conducted clinical trials. […] In short, CPZ repositioning is defined as a new use beyond the field of psychiatry. |