Recent advances in anti-infective drug discovery最新文献

{"title":"Can the Therapeutic Spectrum of Probiotics be Extended: Exploring Potential of Gut Microbiome.","authors":"Sonakshi Rastogi,&nbsp;Aditi Singh,&nbsp;Abhishek Nandy,&nbsp;Akanksha Gupta,&nbsp;Jyotsna Agarwal,&nbsp;Irena Kostova","doi":"10.2174/2772434418666221124124317","DOIUrl":"https://doi.org/10.2174/2772434418666221124124317","url":null,"abstract":"<p><p>Natural therapeutic microorganisms provide a potent alternative healthcare treatment nowadays, with the potential to prevent several human diseases. These health-boosting living organisms, probiotics mostly belong to Gram-positive bacteria such as Lactobacillus, Bifidobacterium, Streptococcus, Saccharomyces, Bacillus and Enterococcus. Initiated almost a century ago, the probiotic application has come a long way. The present review is focused on the potential therapeutic role of probiotics in ameliorating multiple infections, such as upper respiratory tract infections and viral respiratory infections, including COVID-19; liver diseases and hepatic encephalopathy; neurological and psychiatric disorders; autoimmune diseases, particularly rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis. Apart from these, the therapeutic exacerbations of probiotics in urinary tract infections have been extremely promising, and several approaches are reviewed and presented here. We also present upcoming and new thrust areas where probiotic therapeutic interventions are showing promising results, like faecal microbial transplant and vaginal microbial transplant.</p>","PeriodicalId":74643,"journal":{"name":"Recent advances in anti-infective drug discovery","volume":"18 2","pages":"120-147"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9546586","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 Perspective into \"TEL\"-Tenofovir, Emtricitabine and Lamivudine Antileprotic Activities by Drug Repurposing and Exploring the Possibility of Combination Chemotherapy with Drug Rescued Molecules for a Leprosy Free Mankind.","authors":"Pugazhenthan Thangaraju,&nbsp;Sree Sudha Tanguturi Yella,&nbsp;Vijayakumar Arumugam Ramamurthy,&nbsp;Irfan Navabshan,&nbsp;Thameemul Ansari Lappathai Habeeb Mohamed","doi":"10.2174/2772434418666230220123217","DOIUrl":"https://doi.org/10.2174/2772434418666230220123217","url":null,"abstract":"<p><strong>Background: </strong>Since leprosy bacilli cannot grow in vitro, testing for antimicrobial resistance against Mycobacterium leprae or assessing the anti-leprosy activity of new drugs remains hard. Furthermore, developing a new leprosy drug through the traditional drug development process is not economically captivating for pharmaceutical companies. As a result, repurposing existing drugs/approved medications or their derivatives to test their anti-leprotic potency is a promising alternative. It is an accelerated method to uncover different medicinal and therapeutic properties in approved drug molecules.</p><p><strong>Aims: </strong>The study aims to explore the binding potential of anti-viral drugs such as Tenofovir, Emtricitabine, and Lamivudine (TEL) against <i>Mycobacterium leprae</i> using molecular docking.</p><p><strong>Methods: </strong>The current study evaluated and confirmed the possibility of repurposing antiviral drugs such as TEL (Tenofovir, Emtricitabine, and Lamivudine) by transferring the graphical window of the BIOVIA DS2017 with the Crystal Structure of a phosphoglycerate mutase gpm1 from <i>Mycobacterium leprae</i> (PDB ID: 4EO9). Utilizing the smart minimizer algorithm, the protein's energy was reduced in order to achieve a stable local minima conformation.</p><p><strong>Results: </strong>The protein and molecule energy minimization protocol generated stable configuration energy molecules. The protein 4EO9 energy was reduced from 14264.5 kcal/mol to -17588.1 kcal/mol.</p><p><strong>Conclusion: </strong>The CHARMm algorithm-based CDOCKER run docked all three molecules (TEL) inside the 4EO9 protein binding pocket (<i>Mycobacterium leprae</i>). The interaction analysis revealed that tenofovir had a better binding molecule with a score of - 37.7297 kcal/mol than the other molecules.</p>","PeriodicalId":74643,"journal":{"name":"Recent advances in anti-infective drug discovery","volume":"18 3","pages":"170-177"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9573889","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 Prevalence of Blood Borne Diseases in Blood Donors of Peshawar, Khyber Pakhtunkhwa, Pakistan.","authors":"Hafsa Shah,&nbsp;Zia Ur Rahman,&nbsp;Mudassir Khan,&nbsp;Fakhar Zaman,&nbsp;Shahid Badshah","doi":"10.2174/2772434418666230213124806","DOIUrl":"https://doi.org/10.2174/2772434418666230213124806","url":null,"abstract":"<p><strong>Background: </strong>The goal of the study was to investigate the burden of transfusion- transmitted infections (TTIs) hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), syphilis, and malarial parasite (MP) in ABO Blood Groups and Rh Type System among voluntarily blood donors in Khyber Pakhtunkhwa (KPK), Pakistan. It is a retrospective single center cross sectional study. This study was conducted from June 2020 to September 2021 (16 months) at the frontier foundation thalassemia center Peshawar KPK. Donors were physically healthy and fit for donation. Donors with physical disabilities and/or having co-morbid conditions were excluded from the report.</p><p><strong>Methods: </strong>All the samples were screened for anti-HIV, anti-HCV, HBsAg, Syphilis, and Malarial Parasite via ELISA kit and Immune Chromatographic Technique (ICT), respectively. A total of 6311 blood donations were evaluated. The majority of the donations (92%) were from (VNRBD) voluntary non-remunerated blood donation, while only 8% came from replacement donors.</p><p><strong>Results: </strong>Amongst 6311 blood donations, 1.50 % (n = 95) were infected at least with one pathogen, HBV positive cases were 0.855 % (n = 54), HCV positive cases were 0.316% (n = 20), syphilis positive were 0.30% (n = 19) and MP positive cases were only 0.031% (n = 2). HBV, HCV, syphilis and malaria infections rates were found to be low as compared to the previous data published, while no case was reported for HIV. The study also revealed the distribution pattern of the aforementioned pathogens in blood groups and the Rh type system of the reactive samples.</p><p><strong>Conclusion: </strong>The lower reported in our study indicates the awareness among the people of Peshawar about TTIs and their precautions. The prevalence rate that we are reporting is less than previously published articles in the same domain.</p>","PeriodicalId":74643,"journal":{"name":"Recent advances in anti-infective drug discovery","volume":"18 3","pages":"215-220"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9931200","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":"SARS-CoV-2 Pandemic-Therapeutics in Warp Speed.","authors":"Sourav Sen,&nbsp;Nitin Kumar","doi":"10.2174/2772434418666230119101350","DOIUrl":"https://doi.org/10.2174/2772434418666230119101350","url":null,"abstract":"<p><p>Ever since the coronavirus disease 2019 (COVID-19) pandemic struck, the challenges posed to the scientific community by its causative agent, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been countless, and still continue to emerge. Even though a host of repurposed and new therapeutic agents as well as vaccines have been, and are being assessed at a breakneck speed, this contagion continues to create havoc, returning back in waves, with appearance of newer viral variants which are associated with numerous challenges, which include greater transmissibility, increased virulence, immune escape, etc. In this study, we discuss the current status of various therapeutic agents which are being used, or in the various stages of preclinical/clinical trials for managing COVID-19.</p>","PeriodicalId":74643,"journal":{"name":"Recent advances in anti-infective drug discovery","volume":"18 2","pages":"110-119"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9864347","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":"Isoniazid Loaded PCL-PEG Copolymer Nanoparticles for Sustained Release Application.","authors":"Alpana Kulkarni,&nbsp;Priya Betai","doi":"10.2174/2772434418666230228121730","DOIUrl":"https://doi.org/10.2174/2772434418666230228121730","url":null,"abstract":"<p><strong>Background: </strong>Tuberculosis (TB) is still a major cause of death worldwide, despite possibly curable therapies. Neurotoxicity, optic neuritis, and severe liver damage are side effects of isoniazid, a powerful first-line anti-TB drug.</p><p><strong>Objective: </strong>We investigated the use of PCL-PEG copolymer to sustain the release of isoniazid to reduce its adverse effects.</p><p><strong>Methods: </strong>In the present work, PCL-PEG copolymer was synthesized and characterized. Isoniazid-loaded nanoparticles (Inp) were prepared using a PCL-PEG copolymer. Furthermore, a 2³ half factorial design was employed for the optimization of drug and emulsifier concentration in Inp. Full characterization of the nanoparticles was performed in terms of drug loading, entrapment efficiency, particle size, zeta potential, and in vitro drug release. The morphology, FTIR, DSC, and PXRD evaluation of the optimized Batch Inp F13 were studied. Stability was evaluated by storing the freeze-dried Inp F13 at various temperatures.</p><p><strong>Results: </strong>The entrapment efficiency and drug loading of nanoparticles prepared by double emulsion solvent evaporation were found to be the highest. The release study revealed that all batches of nanoparticles exhibited sustained drug release (60.26 - 88.59%) for 5 days. The cytotoxicity study conducted on <i>Mycobacterium tuberculosis </i>revealed a gradual release of isoniazid from Inp, reaching the maximum (on the 15^th day) compared to plain isoniazid (on the 4^th day). At 0.8 μg/mL concentration, the inhibitory activity of Inp F13 was maintained for 15 days, indicating sustained release of isoniazid.</p><p><strong>Conclusion: </strong>The nanoparticles having PCL:PEG in a 95:5 ratio, with 0.5% PVA and initial drug loading of 3 mg, produced the optimum batch. Isoniazid-loaded PCL-PEG nanoparticles allowed controlled (sustained) release of isoniazid.</p>","PeriodicalId":74643,"journal":{"name":"Recent advances in anti-infective drug discovery","volume":"18 3","pages":"221-238"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9947808","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":"Whether Early Steroid dose is Associated with Lower Mortality in COVID-19 Critically Ill Patients-An Exploratory Chart Review.","authors":"Abhishek Goyal,&nbsp;Ankur Joshi,&nbsp;Saurabh Saigal,&nbsp;Dodda Brahmam,&nbsp;Yogesh Niwariya,&nbsp;Alkesh Khurana,&nbsp;Sagar Khadanga,&nbsp;Arun Mitra","doi":"10.2174/2772434417666220817121439","DOIUrl":"https://doi.org/10.2174/2772434417666220817121439","url":null,"abstract":"<p><strong>Introduction: </strong>Steroids have shown its usefulness in critically ill COVID-19 patients. However, the time of starting steroid and dose tailored to severity remain a matter of inquiry due to still emerging evidences and wide-ranging concerns of benefits and harms. We did a retrospective record analysis in an apex teaching hospital ICU setting to explore optimal doses and duration of steroid therapy which can decrease mortality.</p><p><strong>Methods: </strong>114 adults with COVID-19-ARDS admitted to ICU between 20th March-15th August 2020 were included in chart review. We did preliminary exploratory analysis (rooted in steroid therapy matrix categorized by dose and duration) to understand the effect of several covariates on survival. This was followed by univariate and multivariate Cox proportion hazard regression analysis and model diagnostics.</p><p><strong>Results: </strong>Exploratory analysis and visualization indicated age, optimal steroid, severity (measured in P/F) of disease and infection status as potential covariates for survival. Univariate cox regression analysis showed significant positive association of age > 60 years {2.6 (1.5-4.7)} and protective effect of optimum steroid {0.38(0.2-0.72)} on death (hazard) in critically ill patients. Multivariate cox regression analysis after adjusting effect of age showed protective effect of optimum steroid on hazard defined as death {0.46(0.23-0.87), LR = 17.04, (p = 2e-04)}. The concordance was 0.70 and model diagnostics fulfilled the assumption criteria for proportional hazard model.</p><p><strong>Conclusion: </strong>Optimal dose steroid as per defined 'optimum' (<24 hours and doses tailored to P/F at presentation) criteria can offer protective effect from mortality which persists after adjusting for age. This protective effect was not found to be negatively influenced by the risk of infection.</p>","PeriodicalId":74643,"journal":{"name":"Recent advances in anti-infective drug discovery","volume":"18 1","pages":"42-53"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9111169","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":"Meet the Regional Editor","authors":"A. Tsakris","doi":"10.2174/277243441703221110095800","DOIUrl":"https://doi.org/10.2174/277243441703221110095800","url":null,"abstract":"","PeriodicalId":74643,"journal":{"name":"Recent advances in anti-infective drug discovery","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77855522","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":"Meet the Regional Editor","authors":"Michael R. Hamblin","doi":"10.2174/277243441702221007104933","DOIUrl":"https://doi.org/10.2174/277243441702221007104933","url":null,"abstract":"<jats:sec>\u0000<jats:title />\u0000<jats:p />\u0000</jats:sec>","PeriodicalId":74643,"journal":{"name":"Recent advances in anti-infective drug discovery","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81935839","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 study on the bio-responses of a freshwater snail (Biomphalaria alexandrina) to fungal derived compounds.","authors":"A. Mekawey, Salah A R, Mohammed Yosri","doi":"10.2174/2772434417666220610110226","DOIUrl":"https://doi.org/10.2174/2772434417666220610110226","url":null,"abstract":"BACKGROUND\u0000Biomphalaria alexandrina snails, as transitional hosts of schistosomiasis, plays an essential part in spread of the illness. Control of these snails by the substance molluscicides antagonistically influences the oceanic climate, causing poisonous and cancer-causing consequences for non-target life forms.\u0000\u0000\u0000OBJECTIVE\u0000Looking for new naturally safe substances can be used for treatment of schistosomiasis disease with minimal side effects on environment and plants, fish wealth and did not affect on human vital functions.\u0000\u0000\u0000METHODS\u0000Fifty fungal species were used to evaluate their activity against Biomphalaria alexandrina. Study the effect of fungal extract on vital functions of Biomphalaria alexandrina and fish wealth. Purification of active substances and identification of their chemical structures. Results Cladosporium nigrellum and Penicillium aurantiogresium metabolites were effective against B. alexandrina snails, the effects of promising fungal extracts sub-lethal concentrations (IC10 & IC25) on the levels of steroid sex hormones, liver enzymes, total protein, lipids, albumin and glucose were determined. Chemical analyses of this filtrate resulted in the separation of a compound effective against snails; it was identified. Protein electrophoresis showed that fungal filtrate affects the protein pattern of snails' haemolymph. Little or no mortality of Daphnia pulex individuals was observed after their exposure to sub lethal concentrations of each treatment.\u0000\u0000\u0000CONCLUSION\u0000Certain compounds from fungal cultures could be safely used for biological control of Biomphalaria alexandrina snails.","PeriodicalId":74643,"journal":{"name":"Recent advances in anti-infective drug discovery","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82306242","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":"Design, Synthesis, Anti-microbial and Molecular Docking Studies of Novel 5-Pyrazyl-2-Sulfanyl-1, 3, 4-Oxadiazole Derivatives.","authors":"R. Das, D. Mehta, Sumeet Gupta, Meenakshi Dhanawat","doi":"10.2174/2772434417666220609105755","DOIUrl":"https://doi.org/10.2174/2772434417666220609105755","url":null,"abstract":"BACKGROUND\u0000Chemical modification of Oxadiazole may lead to a potent therapeutic agent. A series of novel 5-pyrazyl-2-sulfanyl-1, 3, 4-oxadiazole derivatives (5a-g) have been synthesised utilising pyrazinoic acid as a precursor. The new oxadiazole compounds were docked against potential targets and evaluated for antibacterial and antitubercular activity.\u0000\u0000\u0000METHODS\u0000The 5-pyrazyl-2-substituted sulfanyl-1,3,4-oxadiazole derivatives (5a-g) were synthesized from the crucial intermediate 2-sulfanyl-5-pyrazyl-1,3,4-oxadiazole (4), which was prepared by treating the 2-pyrazyl hydrazide with CS2 and pyridine. IR, 1HNMR, 13C, MS and elemental analyses were used to confirm the chemical structures.\u0000\u0000\u0000RESULTS\u0000Antimicrobial activity was determined for each synthesized compound. Additionally, compounds were evaluated for antitubercular activity against the Mycobacterium Tuberculosis H37Rv strain. Compounds 5c, 5g, and 5a had a favourable antibacterial profile, while 5c and 5g (MIC = 25 g/ml) demonstrated potential antitubercular activity when compared to the other produced compounds. Molecular docking experiments using V-Life Science MDS 4.6 supplemented the biological data.\u0000\u0000\u0000CONCLUSION\u0000Each compound has been tested for antibacterial and antitubercular action against a variety of microorganism strains and exhibits considerable activity. Additionally, molecular docking analysis confirmed the experimental results by describing improved interaction patterns.","PeriodicalId":74643,"journal":{"name":"Recent advances in anti-infective drug discovery","volume":"103 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74371927","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}