Ian Lemuel Sigue Virtucio, J. Punzalan, J. Billones
The COVID-19 pandemic remains to be a global public health crisis due to the emergence of new variants of concern and the scarcity of drug treatments. The cell entry of SARS-CoV-2 requires activation of its spike protein by host proteases TMPRSS2 and CTSL, which triggers membrane fusion and facilitates the endocytic uptake mechanism, respectively. This study employed a structure-based virtual screening technique to identify drugs and natural products that simultaneously target TMPRSS2 and CTSL. Two pharmacophore models were generated from the binding sites of the proteins in complex with their co-crystallized ligands. Both structure-based pharmacophores were used to screen a ligand library composed of 41,775 compounds (10,849 drugs from the ChEMBL database and 30,926 natural products from the NPASS database). A total of 115 compounds (54 drugs and 61 natural products) that fit both TMPRSS2 and CTSL pharmacophore models were identified. The common hits were docked into both proteases to obtain a short list of compounds. Molecular docking filtered 17 compounds (5 drugs and 12 natural products) that have higher binding energy values than the co-crystallized ligands and known inhibitors of both proteins. The top hits were then subjected to ADMET, drug-likeness, and synthetic accessibility filters. Based on docking scores, pharmacokinetics, and drug-likeness, Silibinin was the most promising repurposed drug candidate as a treatment for SARS-CoV-2 infection via dual inhibition of TMPRSS2 and CTSL. Among the natural products, barettin was the best candidate for further development as a novel dual TMPRSS2 and CTSL inhibitor.
{"title":"Virtual Screening for SARS-COV-2 Entry Inhibitors by Dual Targeting of TMPRSS2 and CTSL","authors":"Ian Lemuel Sigue Virtucio, J. Punzalan, J. Billones","doi":"10.51847/6imwqjwvpa","DOIUrl":"https://doi.org/10.51847/6imwqjwvpa","url":null,"abstract":"The COVID-19 pandemic remains to be a global public health crisis due to the emergence of new variants of concern and the scarcity of drug treatments. The cell entry of SARS-CoV-2 requires activation of its spike protein by host proteases TMPRSS2 and CTSL, which triggers membrane fusion and facilitates the endocytic uptake mechanism, respectively. This study employed a structure-based virtual screening technique to identify drugs and natural products that simultaneously target TMPRSS2 and CTSL. Two pharmacophore models were generated from the binding sites of the proteins in complex with their co-crystallized ligands. Both structure-based pharmacophores were used to screen a ligand library composed of 41,775 compounds (10,849 drugs from the ChEMBL database and 30,926 natural products from the NPASS database). A total of 115 compounds (54 drugs and 61 natural products) that fit both TMPRSS2 and CTSL pharmacophore models were identified. The common hits were docked into both proteases to obtain a short list of compounds. Molecular docking filtered 17 compounds (5 drugs and 12 natural products) that have higher binding energy values than the co-crystallized ligands and known inhibitors of both proteins. The top hits were then subjected to ADMET, drug-likeness, and synthetic accessibility filters. Based on docking scores, pharmacokinetics, and drug-likeness, Silibinin was the most promising repurposed drug candidate as a treatment for SARS-CoV-2 infection via dual inhibition of TMPRSS2 and CTSL. Among the natural products, barettin was the best candidate for further development as a novel dual TMPRSS2 and CTSL inhibitor.","PeriodicalId":20012,"journal":{"name":"Pharmacophore","volume":null,"pages":null},"PeriodicalIF":0.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70813710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anamika Singh, Aartiben Rajput, Goshiya Kureshi, G. Carpenter, J. Vashi
{"title":"An RP-HPLC Method Performance and Validation for Azelnidipine Measurment and Metoprolol Succinate Within a Synthetic Mixture","authors":"Anamika Singh, Aartiben Rajput, Goshiya Kureshi, G. Carpenter, J. Vashi","doi":"10.51847/qc9qqmcnoh","DOIUrl":"https://doi.org/10.51847/qc9qqmcnoh","url":null,"abstract":"","PeriodicalId":20012,"journal":{"name":"Pharmacophore","volume":null,"pages":null},"PeriodicalIF":0.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70830926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sandeep Doppalapudi, Vidyadhara Suryadevara, Sai Reshma Ramineni, Aruna Kumar Chadalavada
The current work mainly focused on the determination of the bromelain effect on glucose uptake through the everted gut sac technique. Everted gut sacs are majorly used in evaluating the uptake mechanisms and absorption potential. Bromelain is a natural phytochemical obtained from pineapple. It can alter various body mechanisms. Everted gut sacs were prepared from chick ileum. After thorough cleaning, the gut sacs were filled with Krebs-Henseleit bicarbonate buffer (KHB). Glucose at varying concentrations was added into mucosal compartment fluid. Bromelain was also added to the mucosal compartment with simulated gastric fluid. At time intervals of 5, 10, 15, 20, 30, 45, and 60 min, 0.5ml of samples were collected from the mucosal fluid for glucose level estimation. A kinetic study was also conducted to understand the transport/inhibition of glucose across the intestinal membrane. Incubation of the chick-everted gut sacs with Bromelain at concentrations of 10 and 20μg/mL increased the transport of glucose. The glucose transport was significant at various concentrations i.e., 5.5, 6.5, 7.5, and
{"title":"Assessment of the Effect of Bromelain on Glucose Uptake Using Everted Gut Sac Technique","authors":"Sandeep Doppalapudi, Vidyadhara Suryadevara, Sai Reshma Ramineni, Aruna Kumar Chadalavada","doi":"10.51847/rrhik6lrzc","DOIUrl":"https://doi.org/10.51847/rrhik6lrzc","url":null,"abstract":"The current work mainly focused on the determination of the bromelain effect on glucose uptake through the everted gut sac technique. Everted gut sacs are majorly used in evaluating the uptake mechanisms and absorption potential. Bromelain is a natural phytochemical obtained from pineapple. It can alter various body mechanisms. Everted gut sacs were prepared from chick ileum. After thorough cleaning, the gut sacs were filled with Krebs-Henseleit bicarbonate buffer (KHB). Glucose at varying concentrations was added into mucosal compartment fluid. Bromelain was also added to the mucosal compartment with simulated gastric fluid. At time intervals of 5, 10, 15, 20, 30, 45, and 60 min, 0.5ml of samples were collected from the mucosal fluid for glucose level estimation. A kinetic study was also conducted to understand the transport/inhibition of glucose across the intestinal membrane. Incubation of the chick-everted gut sacs with Bromelain at concentrations of 10 and 20μg/mL increased the transport of glucose. The glucose transport was significant at various concentrations i.e., 5.5, 6.5, 7.5, and","PeriodicalId":20012,"journal":{"name":"Pharmacophore","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135314201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Response Surface Methodology for an Improved Nanoemulsion of Ivacaftor & Its Optimisation for Solubility and Stability","authors":"Akshay Parihar, Bhupendra Gopalbhai Prajapati","doi":"10.51847/izavr2gt5p","DOIUrl":"https://doi.org/10.51847/izavr2gt5p","url":null,"abstract":"Treatment","PeriodicalId":20012,"journal":{"name":"Pharmacophore","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135317861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carmen Corina Radu, Cristian Delcea, Andra Plesa, Dana Rad
This research paper aims to address the pressing concern of drug consumption among youth by utilizing a comprehensive statistical analysis of an intervention program. The study employs the "Intention to Change Behavior Toward Drug Consumption" scale, which is rooted in the Theory of Planned Behavior, to assess participants' intention to alter their drug consumption behavior. The scale encompasses five subscales—attitudes, subjective norms, perceived behavioral control, perceptions of risks, and knowledge of consequences—each probing different components of the theory. The intervention program, named the "Cognitive-Social-Medico-Legal Educational Approach," draws from Albert Bandura's Social Cognitive Theory to affect the behavior and attitude change in youth regarding drug consumption. Grounded in cognitive, behavioral, and environmental factors, the program encompasses observation and modeling, enhancing self-efficacy, employing rewards and punishments, developing self-regulation skills, improving the social environment, and fostering awareness of medico-legal implications. Through a thorough selection methodology, 40 youth actively engaged in drug use and seeking psychotherapy services were chosen for participation—20 in the experimental group and 20 in the control group. After a three-month intervention, statistical analysis revealed significant shifts in attitudes, subjective norms, perceived behavioral control, and knowledge of consequences in the experimental group. Conversely, the control group exhibited limited changes, except for marginal shifts in perceptions of risks. These findings offer critical insights for addressing youth drug consumption through evidence-based interventions, thereby contributing to the larger discourse on substance abuse prevention and empowerment among the youth demographic. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non commercially, as long as the author is credited and the new creations are licensed under the identical terms.
{"title":"Transforming perceptions of drug consumption among youth through a Cognitive-Social-Medico-Legal Educational Approach","authors":"Carmen Corina Radu, Cristian Delcea, Andra Plesa, Dana Rad","doi":"10.51847/oes7yevrmj","DOIUrl":"https://doi.org/10.51847/oes7yevrmj","url":null,"abstract":"This research paper aims to address the pressing concern of drug consumption among youth by utilizing a comprehensive statistical analysis of an intervention program. The study employs the \"Intention to Change Behavior Toward Drug Consumption\" scale, which is rooted in the Theory of Planned Behavior, to assess participants' intention to alter their drug consumption behavior. The scale encompasses five subscales—attitudes, subjective norms, perceived behavioral control, perceptions of risks, and knowledge of consequences—each probing different components of the theory. The intervention program, named the \"Cognitive-Social-Medico-Legal Educational Approach,\" draws from Albert Bandura's Social Cognitive Theory to affect the behavior and attitude change in youth regarding drug consumption. Grounded in cognitive, behavioral, and environmental factors, the program encompasses observation and modeling, enhancing self-efficacy, employing rewards and punishments, developing self-regulation skills, improving the social environment, and fostering awareness of medico-legal implications. Through a thorough selection methodology, 40 youth actively engaged in drug use and seeking psychotherapy services were chosen for participation—20 in the experimental group and 20 in the control group. After a three-month intervention, statistical analysis revealed significant shifts in attitudes, subjective norms, perceived behavioral control, and knowledge of consequences in the experimental group. Conversely, the control group exhibited limited changes, except for marginal shifts in perceptions of risks. These findings offer critical insights for addressing youth drug consumption through evidence-based interventions, thereby contributing to the larger discourse on substance abuse prevention and empowerment among the youth demographic. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non commercially, as long as the author is credited and the new creations are licensed under the identical terms.","PeriodicalId":20012,"journal":{"name":"Pharmacophore","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136207933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cristian Delcea, Dana Rad, Manuela Gyorgy, Remus Runcan, Alina Breaz, Mihaela Gavrilă-Ardelean, Ana Simona Bululoi
{"title":"A Network Analysis Approach to Romanian Resilience - Coping Mechanisms in the Covid-19 Era","authors":"Cristian Delcea, Dana Rad, Manuela Gyorgy, Remus Runcan, Alina Breaz, Mihaela Gavrilă-Ardelean, Ana Simona Bululoi","doi":"10.51847/odzzjcef6o","DOIUrl":"https://doi.org/10.51847/odzzjcef6o","url":null,"abstract":"","PeriodicalId":20012,"journal":{"name":"Pharmacophore","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135784579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Relationship between Sleep and Mental Health among Pregnant Women in Saudi Arabia","authors":"W. Khan","doi":"10.51847/gnbujkdt3o","DOIUrl":"https://doi.org/10.51847/gnbujkdt3o","url":null,"abstract":",","PeriodicalId":20012,"journal":{"name":"Pharmacophore","volume":null,"pages":null},"PeriodicalIF":0.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70821093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Total Polyphenols and Antioxidant Capacity in Different Varieties of Corylus avellana L. Micro-Propagated In vitro","authors":"Sarac Ioan, Stroia Ciprian, Ganea Mariana, Onisan Emilian, Baciu Anca Mihaela, Memete Adriana Ramona, Petrescu Irina","doi":"10.51847/6jupq1hrio","DOIUrl":"https://doi.org/10.51847/6jupq1hrio","url":null,"abstract":"","PeriodicalId":20012,"journal":{"name":"Pharmacophore","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135261943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Felicia Manole, Paula Marian, Gabriel Mihai Mekeres, Andrei Nicolae Csep
{"title":"A Review of the Effects of Pharmaceutical Waste on the Environment and Human Health","authors":"Felicia Manole, Paula Marian, Gabriel Mihai Mekeres, Andrei Nicolae Csep","doi":"10.51847/bi0ovrl99q","DOIUrl":"https://doi.org/10.51847/bi0ovrl99q","url":null,"abstract":"","PeriodicalId":20012,"journal":{"name":"Pharmacophore","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135400828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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