scholarly journals Chemoinformatic Analysis of Psychotropic and Antihistaminic Drugs in the Light of Experimental Anti-SARS-CoV-2 Activities

2021 ◽  
Author(s):  
Bruno Villoutreix ◽  
Rajagopal Krishnamoorthy ◽  
Ryad Tamouza ◽  
Marion Leboyer ◽  
Philippe Beaune
Keyword(s):  
High Throughput Screening ◽  
Psychiatric Patients ◽  
Antiviral Agents ◽  
Clinical Observations ◽  
Prophylactic Drugs ◽  
Initial Hypothesis ◽  
Antihistaminic Drugs ◽  
Vitro Data ◽  
In Vitro Data

<div> <div> <div><b>Introduction:</b> There is an urgent need to identify therapies that prevent SARS-CoV-2 infection and improve the outcome of COVID-19 patients. <p><b>Objective:</b> We proposed, before summer 2020, that cationic amphiphilic psychotropic and antihistaminic drugs could protect psychiatric patients from SARS-CoV-2 infection based upon clinical observations. At that time, experimental in vitro data on SARS-CoV-2 were missing.</p> <p><b>Methods:</b> Open high-throughput screening results are now available at the NCATS COVID-19 portal and it is possible to investigate again our initial hypothesis using simple chemoinformatics approaches but this time with in vitro data on SARS-CoV-2.</p> <p><b>Results and Discussion:</b> We here revisit our initial hypothesis in the light of SARS-CoV-2 experimental screening results and propose that several cationic amphiphilic psychotropic and antihistaminic drugs could protect people from SARS-CoV-2 infection; some of these molecules have very limited adverse effects and could eventually be used as prophylactic drugs. Further, recent analyses of electronic health records reported by several research groups, including drug combinations, indicate that a small list of molecules could be of interest at different stages of the disease progression. Taken together, these observations suggest that clinical trials are now needed to fully evaluate the potentials of these potential small molecules broad-spectrum antiviral agents. Orally available drugs would indeed be of outmost importance to deal with COVID-19.</p> </div> </div> </div>

scholarly journals Chemoinformatic Analysis of Psychotropic and Antihistaminic Drugs in the Light of Experimental Anti-SARS-CoV-2 Activities

2021 ◽  
Author(s):  
Bruno Villoutreix ◽  
Rajagopal Krishnamoorthy ◽  
Ryad Tamouza ◽  
Marion Leboyer ◽  
Philippe Beaune
Keyword(s):  
High Throughput Screening ◽  
Psychiatric Patients ◽  
Antiviral Agents ◽  
Clinical Observations ◽  
Prophylactic Drugs ◽  
Initial Hypothesis ◽  
Antihistaminic Drugs ◽  
Vitro Data ◽  
In Vitro Data

<div> <div> <div><b>Introduction:</b> There is an urgent need to identify therapies that prevent SARS-CoV-2 infection and improve the outcome of COVID-19 patients. <p><b>Objective:</b> We proposed, before summer 2020, that cationic amphiphilic psychotropic and antihistaminic drugs could protect psychiatric patients from SARS-CoV-2 infection based upon clinical observations. At that time, experimental in vitro data on SARS-CoV-2 were missing.</p> <p><b>Methods:</b> Open high-throughput screening results are now available at the NCATS COVID-19 portal and it is possible to investigate again our initial hypothesis using simple chemoinformatics approaches but this time with in vitro data on SARS-CoV-2.</p> <p><b>Results and Discussion:</b> We here revisit our initial hypothesis in the light of SARS-CoV-2 experimental screening results and propose that several cationic amphiphilic psychotropic and antihistaminic drugs could protect people from SARS-CoV-2 infection; some of these molecules have very limited adverse effects and could eventually be used as prophylactic drugs. Further, recent analyses of electronic health records reported by several research groups, including drug combinations, indicate that a small list of molecules could be of interest at different stages of the disease progression. Taken together, these observations suggest that clinical trials are now needed to fully evaluate the potentials of these potential small molecules broad-spectrum antiviral agents. Orally available drugs would indeed be of outmost importance to deal with COVID-19.</p> </div> </div> </div>

scholarly journals Chemoinformatic Analysis of Psychotropic and Antihistaminic Drugs in the Light of Experimental Anti-SARS-CoV-2 Activities

2021 ◽  
Author(s):  
Bruno Villoutreix ◽  
Rajagopal Krishnamoorthy ◽  
Ryad Tamouza ◽  
Marion Leboyer ◽  
Philippe Beaune
Keyword(s):  
High Throughput Screening ◽  
Psychiatric Patients ◽  
Recent Analysis ◽  
Clinical Observations ◽  
Prophylactic Drugs ◽  
Initial Hypothesis ◽  
Antihistaminic Drugs ◽  
Vitro Data ◽  
In Vitro Data

<div> <div> <div><b>Introduction:</b> There is an urgent need to identify therapies that prevent SARS-CoV-2 infection and improve the outcome of COVID-19 patients. <p><b>Objective:</b> We proposed, before summer 2020, that cationic amphiphilic psychotropic and antihistaminic drugs could protect psychiatric patients from SARS-CoV-2 infection based upon clinical observations. At that time, experimental in vitro data on SARS-CoV-2 were missing.</p> <p><b>Methods:</b> Open high-throughput screening results are now available at the NCATS COVID19 portal and it is possible to investigate again our initial hypothesis using simple chemoinformatics approaches but this time with in vitro data on SARS-CoV-2.</p> <p><b>Results and Discussion:</b> We here revisit our hypothesis in the light of SARS-CoV-2 experimental screening results and propose that several cationic amphiphilic psychotropic and antihistaminic drugs could possibly protect people from SARS-CoV-2 infection; some of these molecules have very limited adverse effects and could eventually be used as prophylactic drugs. Further, recent analysis of electronic health records reported by other research groups, including drug combinations, also suggest that a small list of molecules could be of interest at different stages of the disease progression. Taken together, these observations suggest that clinical trials are now needed to fully evaluate the potentials of these molecules.</p> </div> </div> </div>

scholarly journals Chemoinformatic Analysis of Psychotropic and Antihistaminic Drugs in the Light of Experimental Anti-SARS-CoV-2 Activities

2021 ◽  
Author(s):  
Bruno Villoutreix ◽  
Rajagopal Krishnamoorthy ◽  
Ryad Tamouza ◽  
Marion Leboyer ◽  
Philippe Beaune
Keyword(s):  
Experimental Data ◽  
Clinical Trials ◽  
Adverse Effects ◽  
High Throughput ◽  
High Throughput Screening ◽  
Psychiatric Patients ◽  
Clinical Observations ◽  
Prophylactic Drugs ◽  
Advanced Stages ◽  
Antihistaminic Drugs

<div> <div> <div> <p>There is an urgent need to identify therapies that prevent SARS-CoV-2 infection and improve the outcome of COVID-19 patients. We proposed before summer 2020 that cationic amphiphilic psychotropic and antihistaminic drugs could protect psychiatric patients from SARS-CoV-2 infection based upon clinical observations. At that time, experimental data on SARS-CoV-2 were missing but today, open high-throughput screening results are available at the NCATS COVID19 portal. We here revisit our hypothesis in the light of these data and we propose that several cationic amphiphilic psychotropic and antihistaminic drugs could be valuable to protect people from SARS-CoV-2 infection, they should have very limited adverse effects and could possibly be used as prophylactic drugs. Recent studies also suggest that some of these molecules could be valuable in more advanced stages of the disease progression. Clinical trials are now needed to fully evaluate the potentials of these molecules. </p> </div> </div> </div>

scholarly journals Chemoinformatic Analysis of Psychotropic and Antihistaminic Drugs in the Light of Experimental Anti-SARS-CoV-2 Activities

2021 ◽  
Author(s):  
Bruno Villoutreix ◽  
Rajagopal Krishnamoorthy ◽  
Ryad Tamouza ◽  
Marion Leboyer ◽  
Philippe Beaune
Keyword(s):  
Experimental Data ◽  
Clinical Trials ◽  
Adverse Effects ◽  
High Throughput ◽  
High Throughput Screening ◽  
Psychiatric Patients ◽  
Clinical Observations ◽  
Prophylactic Drugs ◽  
Advanced Stages ◽  
Antihistaminic Drugs

<div> <div> <div> <p>There is an urgent need to identify therapies that prevent SARS-CoV-2 infection and improve the outcome of COVID-19 patients. We proposed before summer 2020 that cationic amphiphilic psychotropic and antihistaminic drugs could protect psychiatric patients from SARS-CoV-2 infection based upon clinical observations. At that time, experimental data on SARS-CoV-2 were missing but today, open high-throughput screening results are available at the NCATS COVID19 portal. We here revisit our hypothesis in the light of these data and propose that several cationic amphiphilic psychotropic and antihistaminic drugs could be valuable to protect people from SARS-CoV-2 infection, they should have very limited adverse effects and could possibly be used as prophylactic drugs. Recent studies also suggest that some of these molecules could be of interest in more advanced stages of the disease progression. Clinical trials are now needed to fully evaluate the potentials of these molecules. </p> </div> </div> </div>

scholarly journals Insights and Perspectives on Emerging Inputs to Weight of Evidence Determinations for Food Safety: Workshop Proceedings

2013 ◽  
Vol 32 (6) ◽  
pp. 405-414 ◽  
Author(s):  
Heidi Bialk ◽  
Craig Llewellyn ◽  
Alison Kretser ◽  
Richard Canady ◽  
Richard Lane ◽  
...  
Keyword(s):  
Food Safety ◽  
In Silico ◽  
High Throughput Screening ◽  
Weight Of Evidence ◽  
Food Ingredient ◽  
Food Ingredients ◽  
Safety Assessments ◽  
Vitro Data ◽  
In Vitro Data

This workshop aimed to elucidate the contribution of computational and emerging in vitro methods to the weight of evidence used by risk assessors in food safety assessments. The following issues were discussed: using in silico and high-throughput screening (HTS) data to confirm the safety of approved food ingredients, applying in silico and HTS data in the process of assessing the safety of a new food ingredient, and utilizing in silico and HTS data in communicating the safety of food ingredients while enhancing the public’s trust in the food supply. Perspectives on integrating computational modeling and HTS assays as well as recommendations for optimizing predictive methods for risk assessment were also provided. Given the need to act quickly or proceed cautiously as new data emerge, this workshop also focused on effectively identifying a path forward in communicating in silico and in vitro data.

scholarly journals Main protease mutants of SARS-CoV-2 variants remain susceptible to PF-07321332

2021 ◽  
Author(s):  
Sven Ullrich ◽  
Kasuni B Ekanayake ◽  
Gottfried Otting ◽  
Christoph Nitsche
Keyword(s):  
Public Health ◽  
Clinical Relevance ◽  
Drug Targets ◽  
Antiviral Agents ◽  
Spike Protein ◽  
Main Protease ◽  
Public Health Threat ◽  
Vitro Data ◽  
In Vitro Data

The COVID-19 pandemic continues to be a public health threat. Multiple mutations in the spike protein of emerging variants of SARS-CoV-2 appear to impact on the effectiveness of available vaccines. Specific antiviral agents are keenly anticipated but their efficacy may also be compromised in emerging variants. One of the most attractive coronaviral drug targets is the main protease (Mpro). A promising Mpro inhibitor of clinical relevance is the peptidomimetic PF-07321332. We expressed Mpro of five SARS-CoV-2 lineages (C.37 Lambda, B.1.1.318, B.1.2, B.1.351 Beta, P.2 Zeta), each of which carries a strongly prevalent missense mutation (G15S, T21I, L89F, K90R, L205V). Enzyme kinetics showed that these Mpro variants are similarly catalytically competent as the wildtype. We show that PF-07321332 has similar potency against the variants as against the wildtype. Our in vitro data suggest that the efficacy of specific Mpro inhibitors such as PF-07321332 is not compromised in current COVID-19 variants.

Use of Toxicokinetics in Risk Assessment Based on In Vitro Data

1993 ◽  
Vol 21 (2) ◽  
pp. 173-180
Author(s):  
Gunnar Johanson
Keyword(s):  
Risk Assessment ◽  
Whole Body ◽  
External Exposure ◽  
Target Dose ◽  
Toxic Response ◽  
Route Of Exposure ◽  
Vitro Data ◽  
In Vitro Data

This presentation addresses some aspects of the methodology, advantages and problems associated with toxicokinetic modelling based on in vitro data. By using toxicokinetic models, particularly physiologically-based ones, it is possible, in principle, to describe whole body toxicokinetics, target doses and toxic effects from in vitro data. Modelling can be divided into three major steps: 1) to relate external exposure (applied dose) of xenobiotic to target dose; 2) to establish the relationship between target dose and effect (in vitro data, e.g. metabolism in microsomes, partitioning in tissue homogenates, and toxicity in cell cultures, are useful in both steps); and 3) to relate external exposure to toxic effect by combining the first two steps. Extrapolations from in vitro to in vivo, between animal and man, and between high and low doses, can easily be carried out by toxicokinetic simulations. In addition, several factors that may affect the toxic response by changing the target dose, such as route of exposure and physical activity, can be studied. New insights concerning the processes involved in toxicity often emerge during the design, refinement and validation of the model. The modelling approach is illustrated by two examples: 1) the carcinogenicity of 1,3-butadiene; and 2) the haematotoxicity of 2-butoxyethanol. Toxicokinetic modelling is an important tool in toxicological risk assessment based on in vitro data. Many factors, some of which can, and should be, studied in vitro, are involved in the expression of toxicity. Successful modelling depends on the identification and quantification of these factors.

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