Infectious disorders drug targets最新文献

{"title":"Design of RNA Polymerase Inhibitors as Therapeutics for Tuberculous Meningitis.","authors":"Varalakshmi Vummidi, Sekhar Talluri","doi":"10.2174/0118715265341228240827062721","DOIUrl":"10.2174/0118715265341228240827062721","url":null,"abstract":"<p><strong>Background: </strong>Tuberculosis is an infectious disease caused by Mycobacterium tuber-culosis. The current treatment protocols for pulmonary tuberculosis are quite effective, even though the treatment requires 3-6 months. The current treatment protocols for extrapulmonary tuberculosis are based on the same drugs that are used for pulmonary tuberculosis. However, the success rates are much lower for certain types of extrapulmonary tuberculosis, such as tubercu-lous meningitis. Tuberculous meningitis is one of the very few diseases attributable to bacteria that have a very high short-term mortality rate among diagnosed patients, even after treatment with antibiotics that are effective for pulmonary tuberculosis. For example, rifampicin is highly effective for the treatment of pulmonary tuberculosis, but its effectiveness for the treatment of tuberculous meningitis is much lower. The reason for the lower effectiveness of rifampicin against tuberculous meningitis is that it has low Blood-Brain Barrier (BBB) permeability, which results in lower concentrations of the drug at the required sites in the central nervous system.</p><p><strong>Methods: </strong>In this work, ligands having improved BBB permeability and pharmacokinetic and pharmacodynamic properties, either similar to or better than that of rifampicin, have been designed. The BBB permeability of the designed molecules was assessed by using pkCSM, a machine-learning model. Pharmacokinetic properties, drug-likeness, and synthesizability were assessed by using SWISS-MODEL. The binding affinity of the designed drugs was assessed by using AutoDock Vina. A customized scoring function, StWN score, was used for a quantitative weighted assessment of all the properties of interest to rank the designed molecules.</p><p><strong>Results: </strong>In this study, drug-like ligands have been designed that have been predicted to have high BBB permeability as well as high affinity for RNA polymerase β of Mycobacterium tuberculosis.</p><p><strong>Conclusion: </strong>The best ligands generated by the tools employed were selected as potential drugs to address the current need for better options for the treatment of tuberculous meningitis.</p>","PeriodicalId":101326,"journal":{"name":"Infectious disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121498","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":"Characterization of Antibiotic Actinomycin D Isolated from Streptomyces parvulus Collected from Marine Sponge of Barrang Lompo Island, Makassar, Indonesia.","authors":"Herlina Rante, Gemini Alam, Yosi Bayu Murti, Alimuddin Ali","doi":"10.2174/0118715265306848240719061135","DOIUrl":"https://doi.org/10.2174/0118715265306848240719061135","url":null,"abstract":"<p><strong>Background: </strong>Microorganisms associated with sea sponges have proven to be good natural product resources that are biologically active and pharmaceutically important.</p><p><strong>Objective: </strong>This research aimed to identify actinomycetes related to a sponge from Bar-ranglompo Island Makassar and the antibacterial compounds.</p><p><strong>Methods: </strong>Identification of actinomycetes was based on molecular characterization of sequence gen16S rRNA. The antibacterial compound was separated using vacuum liquid chromatog-raphy and preparative Thin Layer Chromatography (TLC). The structure determination was done based on spectroscopy 1H-NMR, 13C-NMR, 2D NMR, and mass spectra.</p><p><strong>Results: </strong>Molecular characterization showed that actinomycetes strain BLP 20 had the closest relationship with Streptomyces parvulus and Uncultured Streptomyces sp. with a similarity value of 83%. The results obtained from the characterization of antibacterial compounds based on spectroscopic data indicate that these compounds lead to Actinomycin D.</p><p><strong>Conclusion: </strong>Characterization and identification of Strain 20 / BLP by molecular phylogenetic analysis of 16S rRNA sequences revealed the closest relationship with Uncultured Streptomy-ces sp and S. parvulus with a similarity value of 83 %, which indicated a new species. The structure of the active compound isolated from actinomycetes strain 20 / BLP leads to Actino-mycin D.</p>","PeriodicalId":101326,"journal":{"name":"Infectious disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142083030","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":"A Review on the Epidemiology and Clinical Management of Neglected Tropical Diseases.","authors":"Medha Dwivedi, Aiswarya Pawar, Mahima Kori, Hitendra Yadav, Manish Dwivedi","doi":"10.2174/0118715265305007240718081727","DOIUrl":"https://doi.org/10.2174/0118715265305007240718081727","url":null,"abstract":"<p><p>Infectious disorders known as Neglected Tropical Diseases (NTDs) initially affect the world's underprivileged citizens. They have been disregarded for many years, first as a result of a general indifference to such a developing world and, more recently, as an outcome of the intense attention on AIDS, TB, and malaria. Tropical diseases mostly affect the region where health and hygiene are sacrificed, and most of the population lacks access to sufficient food and living resources. WHO has drafted and released the directions for regulation, pre-vention, and successful eradication of NTDs as per the revised roadmap of 2021-2030. This shifts from vertical disease programs to integrated cross-cutting methods. In the current work, we have provided comprehensive information on various aspects of neglected tropical dis-eases, including the clinical management of NTDs. This encompasses the causative agent of the diseases, their symptoms, pathogenesis, diagnosis, treatment, prognosis, and epidemio-logical perspective of major NTDs. This review will shed light on several perspectives of NTDs having influential roles in proposing strategies to control and treat them around the world.</p>","PeriodicalId":101326,"journal":{"name":"Infectious disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057804","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":"Drug Discovery and Exploration of Heterocycles for the Development of Anti-HIV Agents.","authors":"Mayura A Kale, Mamata V Jain","doi":"10.2174/0118715265290911240611072422","DOIUrl":"https://doi.org/10.2174/0118715265290911240611072422","url":null,"abstract":"<p><p>It is a known fact that HIV infection remains a serious public health problem throughout the world, and the need to constantly develop new antiretroviral drugs to combat HIV emerges from the fact that repetitive mutations occurring in viral enzymes make this virus resistant to antiretroviral drugs. This resistance causes failure of treatment, and hence, for many years, extensive research has been to discover newer possibilities for fighting this disease at a molecular level, along with many long-standing and expensive clinical trials. Many scientific research programs have either been discarded or unsuccessful. However, the research has not stopped, and in the process, many heterocyclic scaffolds have been used to build up novel drug molecules to combat this disease. A literature survey reveals that many heterocycles have been explored and were found to be very useful in treating different types of viral infections. This concise and rigorous literature explains the journey and highlights the various strategies to develop new anti-HIV drug candidates.</p>","PeriodicalId":101326,"journal":{"name":"Infectious disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057779","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":"A Review of the Difficulties Faced by Low and Middle-income Countries in Hygiene and Healthcare Practices.","authors":"Jashan Girdhar, Kapil Shandilya, Munnawar Husaain, Parneet Kaur, Shushank Mahajan, Tarun Singh, Isha Chawla, Meenakshi Dhanawat","doi":"10.2174/0118715265307717240713182628","DOIUrl":"https://doi.org/10.2174/0118715265307717240713182628","url":null,"abstract":"<p><p>Hygiene has been identified as an important step in anticipating health-related pol-lution, with conflicting reports about consistent sanitation standards in the nation. This narrative review of published studies has led to the discussion of hand hygiene and health practices, as well as the identification of necessary methods that are available in low and middle-income countries. An effective survey of accessible information is conducted in this way based on re-view questions. A number of 372 articles were found on the web, and 32 articles were used in the final analysis. Overall, the standard of hand hygiene is set at 20.49%. Difficulties identified for the people in low or middle-income countries are poor awareness and sound information about hand hygiene, lack of resources including water, soap, hand scrubbing gel, etc., as mis-interpretations related to hand hygiene practices. People are paying more attention to healthcare-related illnesses as it becomes increasingly clear that most of them may be pre-vented. The free evidence-based practice states that to lower the danger of contamination, hand hygiene should be properly adhered to. The difficulties recognized in this review are reliable, with the discoveries of studies that have been led somewhere else. By conducting a basic ex-amination of the \"Clean Care is Safer Care\" as an excellent arrangement of WHO's global initiative activity on patient well-being programs, developing nations will have more time to consider the essential approaches for the use of fundamental disease prevention exercises in our health care settings.</p>","PeriodicalId":101326,"journal":{"name":"Infectious disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006218","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":"The Human Monkeypox Virus and Host Immunity: Emerging Diagnostic and Therapeutic Challenges.","authors":"Vijay Singh, Shailendra Dwivedi, Ruchika Agrawal, Sadashiv, Ghizal Fatima, Afroz Abidi","doi":"10.2174/0118715265309361240806064619","DOIUrl":"https://doi.org/10.2174/0118715265309361240806064619","url":null,"abstract":"<p><p>This article explores the Human Monkeypox Virus (MPV), a contagious virus that causes disease in both vertebrates and insects. It originated in Denmark in 1958 and expanded beyond Africa during the 1970s. The virus was initially detected in the United States in 2003 following the hospitalisation of a toddler who had been bitten by a prairie dog. The article examines the identification of the virus, its categorization into two genetic groups with dif-ferent levels of harmfulness, and its genetic changes over time due to specific influences. Additionally, it investigates the immunological reaction to MPXV, encompassing both the innate and adaptive systems. The essay also addresses the diagnostic difficulties presented by MPXV's resemblance to other orthopoxviruses and the progress made in molecular diagnos-tics. The paper analyses different therapeutic interventions, such as tecovirimat, an antiviral medication, and JYNNEOS, a vaccine, in terms of their efficacy, potential drawbacks, and the difficulties encountered in managing outbreaks. The future outlook emphasises the ne-cessity of inventive research methodologies, worldwide monitoring, and individualised med-ical treatments to counteract the dissemination of MPXV and alleviate its consequences on public health.</p>","PeriodicalId":101326,"journal":{"name":"Infectious disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006256","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":"Confronting and Addressing the Presence of Psittacosis in Europe.","authors":"Shivang Saxena, Shubhi Saxena, Nihar Ranjan Sahoo, Amandeep Singh","doi":"10.2174/0118715265322768240807102042","DOIUrl":"https://doi.org/10.2174/0118715265322768240807102042","url":null,"abstract":"","PeriodicalId":101326,"journal":{"name":"Infectious disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006219","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":"Screening and Identification of Natural Compounds as Potential Inhibitors of Glutamate Racemase, an Emerging Drug Target of Food Pathogen E. coli O157:H7: An In-silico Approach to Combat Increasing Drug Resistance","authors":"Rajnish Kumar, Samarth Gupta, Sujata Adhana, Anoushka Khanna, Sibasis Sahoo, Muniba Faiza, Renu Baweja, Archna Pandey, Avneesh Mittal, Uma Chaudhry","doi":"10.2174/0118715265306131240809095241","DOIUrl":"10.2174/0118715265306131240809095241","url":null,"abstract":"<p><strong>Background: </strong>Shiga Toxin-Producing Escherichia coli (E. coli O157:H7), capable of causing serious food-borne illnesses, is extensively studied and is known to be transmitted through animal reservoirs or person-to-person contact, leading to severe disease outbreaks. The emergence of antibiotic resistance in these strains, coupled with increased adverse effects of existing therapeutics, underscores the urgent need for alternative therapeutic strategies.</p><p><strong>Objective: </strong>This study aims to evaluate Glutamate Racemase (MurI protein) of the food-path-ogenic E. coli O157:H7 (EC MurI) as a novel drug target. Furthermore, the study seeks to identify new compounds with potential inhibitory effects against this protein.</p><p><strong>Methods: </strong>Using computational tools, the study identified inhibitor binding sites on EC MurI and identified relevant inhibitors capable of binding to these sites. Molecular docking tech-niques were employed to assess potential hits, and selected compounds were further analyzed for their structural activity and binding affinity to the protein.</p><p><strong>Results: </strong>The results of the study revealed that Frigocyclinone and Deslanoside, exhibited the best binding affinity with EC-MurI. Subsequent molecular dynamic (MD) simulations of the selected complexes indicated that both compounds were stable. This suggests that Frigocy-clinone and Deslanoside have the potential to serve as potent inhibitors of EC-MurI.</p><p><strong>Conclusion: </strong>In summary, this study highlights the urgent need for alternative therapies against food-pathogenic E. coli, focusing on E. coli O157:H7. Evaluation of Glutamate Race-mase as a drug target identified Frigocyclinone and Deslanoside as promising inhibitors. MD simulations indicated their stability, suggesting their potential as lead molecules for further research and treatment development.</p>","PeriodicalId":101326,"journal":{"name":"Infectious disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006220","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":"Echoes of the Black Death: Yersinia Pestis Resurgence and Public Health Perspectives.","authors":"Anish Soni, Prabhjot Kaur, Naresh Kumar Rangra","doi":"10.2174/0118715265318459240721195503","DOIUrl":"https://doi.org/10.2174/0118715265318459240721195503","url":null,"abstract":"","PeriodicalId":101326,"journal":{"name":"Infectious disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141904118","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":"A Comparison of Antibiotics' Resistance Patterns of E. coli and B. Subtilis in their Biofilms and Planktonic Forms.","authors":"Shagun Sharma, Vandana Jhalora, Shubhita Mathur, Renu Bist","doi":"10.2174/0118715265278809240101073539","DOIUrl":"https://doi.org/10.2174/0118715265278809240101073539","url":null,"abstract":"<p><strong>Background: </strong>A biofilm refers to a community of microbial cells that adhere to surfaces that are surrounded by an extracellular polymeric substance. Bacteria employ various defence mechanisms, including biofilm formation, to enhance their survival and resistance against antibiotics.</p><p><strong>Objective: </strong>The current study aims to investigate the resistance patterns of Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis) in both biofilms and their planktonic forms.</p><p><strong>Methods: </strong>E. coli and B. subtilis were used to compare resistance patterns in biofilms versus planktonic forms of bacteria. An antibiotic disc diffusion test was performed to check the resistance pattern of biofilm and planktonic bacteria against different antibiotics such as penicillin G, streptomycin, and ampicillin. Biofilm formation and its validation were done by using quantitative (microtiter plate assay) and qualitative analysis (Congo red agar media).</p><p><strong>Results: </strong>A study of surface-association curves of E. coli and B. subtilis revealed that surface adhesion in biofilms was continuously constant as compared to their planktonic forms, thereby confirming the increased survival of bacteria in biofilms. Also, biofilms have shown high resistance towards the penicillin G, ampicillin and streptomycin as compared to their planktonic form.</p><p><strong>Conclusion: </strong>It is safely inferred that E. coli and B. subtilis, in their biofilms, become increasingly resistant to penicillin G, ampicillin and streptomycin.</p>","PeriodicalId":101326,"journal":{"name":"Infectious disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141877168","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}