Drugs and Drug Candidates最新文献_第5页

Date (Phoenix dactylifera L.) Fruits as a Potential Lipid-Lowering Therapy: Effect on High-Fat Diet and Triton-WR-1339-Induced Hyperlipidemic Rats 枣(凤凰花)水果作为一种潜在的降脂疗法:对高脂肪饮食和triton - wr -1339诱导的高脂血症大鼠的影响

Drugs and Drug Candidates Pub Date : 2023-05-30 DOI: 10.3390/ddc2020021

Eimad Dine Tariq Bouhlali, Abdelbassat Hmidani, Bouchra Bourkhis, Zineb Moussafir, Younes Filali-Zegzouti, Chakib Alem

{"title":"Date (Phoenix dactylifera L.) Fruits as a Potential Lipid-Lowering Therapy: Effect on High-Fat Diet and Triton-WR-1339-Induced Hyperlipidemic Rats","authors":"Eimad Dine Tariq Bouhlali, Abdelbassat Hmidani, Bouchra Bourkhis, Zineb Moussafir, Younes Filali-Zegzouti, Chakib Alem","doi":"10.3390/ddc2020021","DOIUrl":"https://doi.org/10.3390/ddc2020021","url":null,"abstract":"The present study was designed to establish the phenolic profile and explore the potential lipid-lowering effect of two Moroccan date fruit varieties (Majhoul and Bousrdoun). HPLC-DAD has been used for phenolic profiling. Lipid peroxidation was measured in terms of thiobarbituric acid-reactive substances (TBARS) by using egg yolk homogenate as lipid-rich media. The anti-hyperlipidemic effect of the methanolic extract was examined using both models Triton-WR-1339 and chronic high-fat-diet-induced hyperlipemic rats. Further, the serum lipid profile was determined. The HPLC-DAD analysis revealed the presence of seven phenolic acids and three flavonoids, of which gallic, caffeic acids and rutin were found to be the most abundant compounds. The gathered results indicate that rats treated with both varieties showed a significant decrease in serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels as well as an increase in high-density lipoprotein cholesterol levels compared with Triton and high-fat diet controls. Moreover, a significant decrease in body weight was observed in the date-treated groups when compared to the hyperlipidemic control group. A thiobarbituric acid reactive substances test showed that these extracts significantly inhibited lipid peroxidation. Bousrdoun, which showed the highest lipid-lowering effects, is the one that displayed the greatest inhibition of lipid peroxidation and contains the largest amount of caffeic, p-coumaric, gallic, vanillic acids, rutin and luteolin. Accordingly, dates could be used as a potential functional food, which may be used to prevent lipid disorders and oxidation.","PeriodicalId":131152,"journal":{"name":"Drugs and Drug Candidates","volume":"41 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135643229","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}

引用次数: 0

How Far Have We Developed Antibody–Drug Conjugate for the Treatment of Cancer? 抗体-药物偶联物治疗癌症的进展如何?

Drugs and Drug Candidates Pub Date : 2023-05-23 DOI: 10.3390/ddc2020020

Yu Jun Lim, Pei Sze Clarissa Lau, Shi Xuan Low, Shong Li Ng, Min Yee Ong, Huey Ming Pang, Z. Lee, H. Yow, S. Hamzah, R. Sellappans, J. Foo

{"title":"How Far Have We Developed Antibody–Drug Conjugate for the Treatment of Cancer?","authors":"Yu Jun Lim, Pei Sze Clarissa Lau, Shi Xuan Low, Shong Li Ng, Min Yee Ong, Huey Ming Pang, Z. Lee, H. Yow, S. Hamzah, R. Sellappans, J. Foo","doi":"10.3390/ddc2020020","DOIUrl":"https://doi.org/10.3390/ddc2020020","url":null,"abstract":"Cancer, also known as malignant tumour or neoplasm, is a leading cause of death worldwide. One distinct feature from normal cells is that cancerous cells often overexpress protein on the cell membrane—for instance, the overexpression of human epidermal growth factor receptor 2. The expression of a specific protein on the cancerous cell surface acts as a marker that differentiates the normal cell and facilitates the recognition of cancerous cells. An emerging anticancer treatment, Antibody–Drug Conjugates (ADCs), utilises this unique feature to kill cancerous cells. ADCs consist of an antibody linked with a cytotoxic payload, mainly targeting the antigen found on cancerous cells. This design can increase the specificity in delivering the cytotoxin to the drug target, thus increasing the drug efficacy and reducing the side effect of cancer treatment due to off-target toxicities. There are tremendous quantities of clinical trials conducted to evaluate the safety and effectiveness of this magic drug in treating different types of cancers. However, only 12 ADCs have been approved by the FDA until now. This review provides the principles of ADCs and highlights the ADCs that FDA has approved. In addition, some of the ADCs that undergo clinical trials are discussed in this review. The application of computational techniques in addressing ADCs’ challenges and neoantigen-targeted cancer vaccines is also highlighted. Although ADCs have been seen as promising magic drugs in cancer treatment, the problems such as toxicity, the stability of the linker, the specificity of an antibody with antigen, and so on, remain a challenge in developing ADCs.","PeriodicalId":131152,"journal":{"name":"Drugs and Drug Candidates","volume":"134 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131965674","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}

引用次数: 0

Reduction of Cancer Stem Cells and Invasiveness of Human Melanoma and Breast Cancer by Cucurbitacin B from Lagenaria siceraria 瓜素B对肿瘤干细胞的抑制作用及对人黑色素瘤和乳腺癌的侵袭作用

Drugs and Drug Candidates Pub Date : 2023-05-22 DOI: 10.3390/ddc2020019

Cheng‐chen Huang, Kiera K. Balding, Sydney J. Zimmerman, Che-Yuan Chang, S. Lu, Hui-Chi Huang

{"title":"Reduction of Cancer Stem Cells and Invasiveness of Human Melanoma and Breast Cancer by Cucurbitacin B from Lagenaria siceraria","authors":"Cheng‐chen Huang, Kiera K. Balding, Sydney J. Zimmerman, Che-Yuan Chang, S. Lu, Hui-Chi Huang","doi":"10.3390/ddc2020019","DOIUrl":"https://doi.org/10.3390/ddc2020019","url":null,"abstract":"Cucurbitacins are secondary metabolites that are commonly found in the Cucurbitacae family. Many biological properties have been reported for cucurbitacins, including anti-inflammatory, antioxidant, antiviral, anti-malaria, and anticancer properties. While studies for the anticancer property of cucurbitacins focus mostly on the cell-cycle progression and apoptosis, no study has considered the effect of cucurbitacin on other cancer behaviors. Here, we report cell-proliferation-based drug testing on random herbal extracts leading to the identification of cucurbitacin B as an anticancer compound. Interestingly, cucurbitacin B had no effect on the proliferation of rat embryonic myoblast cells. We also found that cucurbitacin B significantly reduced the invasiveness of at least two highly metastatic breast cancer and melanoma cells. Using known cancer stem-cell markers, we observed a significant reduction of the melanoma stem cells. Molecularly, cucurbitacin B caused reduction of the metastasis-promoting gene Snail in melanoma and one of the cancer stem cell markers, ALDH1A1 (aldehyde dehydrogenase 1 A1), in breast cancer. Finally, we report the potential toxicity of cucurbitacin B in developing skin tissue and the olfactory organ using zebrafish embryo. In summary, our study suggests the potential use of cucurbitacin B for cancer metastasis and relapse treatment.","PeriodicalId":131152,"journal":{"name":"Drugs and Drug Candidates","volume":"113 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124699645","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}

引用次数: 0

The Readiness to Harness the Floristic Uniqueness of Mauritius in Biomedicine 准备利用毛里求斯在生物医学上的独特植物区系

Drugs and Drug Candidates Pub Date : 2023-05-10 DOI: 10.3390/ddc2020018

N. Rummun, V. Neergheen

{"title":"The Readiness to Harness the Floristic Uniqueness of Mauritius in Biomedicine","authors":"N. Rummun, V. Neergheen","doi":"10.3390/ddc2020018","DOIUrl":"https://doi.org/10.3390/ddc2020018","url":null,"abstract":"Resistance to the existing arsenal of therapeutic agents significantly impedes successful drug therapy. One approach to combat this burgeoning global crisis is to provide novel and more effective clinical agents. Terrestrial plants have long been exploited as a source of novel drug candidates. In this line, the endemic floral diversity of the Republic of Mauritius cannot be ignored. However, developing drugs from these plants is a multi-stepped, lengthy process that requires multistakeholder involvement from scientists, policymakers, and conservationists as well as the local community. This review aims at summarising the reported bioactivities of the endemic plants. The electronic databases were searched using relevant keywords. A total of 33 original research articles were considered. A repertoire of 17 families comprising 53 Mauritian-endemic plant species has been reported for their anticancer activity (n = 20), antimicrobial activity (n = 36), antidiabetic activity (n = 3), and clinical enzyme inhibitory activity (n = 25). Five plant extracts, namely Acalypha integrifolia, Labourdonaisia glauca, Eugenia tinifolia, Syzygium coriaceum, and Terminalia bentzoë, have been earmarked as worthy to be further investigated for their anticancer potential. Moreover, two Psiadia species, namely P. arguta and P. terebinthina, have shown promising antimicrobial activity. This review highlights the extracts’ potent anticancer and antimicrobial activities, focussing on their proposed mechanism of action. Moreover, the need for metabolite profiling for identifying bioactive ingredient(s) is emphasised.","PeriodicalId":131152,"journal":{"name":"Drugs and Drug Candidates","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122593642","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}

引用次数: 0

Virtual Screening Algorithms in Drug Discovery: A Review Focused on Machine and Deep Learning Methods 药物发现中的虚拟筛选算法:基于机器和深度学习方法的综述

Drugs and Drug Candidates Pub Date : 2023-05-05 DOI: 10.3390/ddc2020017

Tiago Alves de Oliveira, Michel Pires da Silva, Eduardo H. B. Maia, Alisson Marques da Silva, A. Taranto

引用次数: 2

Synergistic Interaction of Glycyrrhizin with Norfloxacin Displays ROS-Induced Bactericidal Activity against Multidrug-Resistant Staphylococcus aureus 甘草酸与诺氟沙星协同作用显示ros诱导的对多重耐药金黄色葡萄球菌的杀菌活性

Drugs and Drug Candidates Pub Date : 2023-04-26 DOI: 10.3390/ddc2020016

Vigyasa Singh, A. Pal, M. Darokar

{"title":"Synergistic Interaction of Glycyrrhizin with Norfloxacin Displays ROS-Induced Bactericidal Activity against Multidrug-Resistant Staphylococcus aureus","authors":"Vigyasa Singh, A. Pal, M. Darokar","doi":"10.3390/ddc2020016","DOIUrl":"https://doi.org/10.3390/ddc2020016","url":null,"abstract":"Acquired bacterial resistance against several antibiotics has severely impaired the drug treatment regime. Multidrug-resistant Staphylococcus aureus (MDRSA) causes several life-threatening human pathologies. The introduction of novel antibiotics is a tedious process. Therefore, we have introduced glycyrrhizin (Gly) as a bioenhancer of norfloxacin (Nor), which showed synergistic interactions and a robust drug response. The drug resistance reversal potential of Gly against MDRSA was monitored. Gly and GlyNor (glycyrrhizin + norfloxacin) were used for spectrofluorometer and flow cytometry analysis for the measurement of free radicals and its effect upon cell membranes and macromolecules. Morphological analysis was carried out with the help of SEM. qRT-PCR analysis was conducted for gene regulation. Gly was observed to lower the MIC (minimum inhibitory concentration) of different groups of antibiotics up to 64-fold against MDRSA. GlyNor exerted oxidative stress, as evidenced by the measurement of reactive oxygen species (ROS) and their effect upon cell components. Gly and GlyNor showed membrane damage potential. The expression analysis of oxidative-related and MDR genes showed the up- and downregulation of these genes, respectively. GlyNor significantly lengthened post-antibiotic effects (PAE) and showed reduced mutation frequency rate (MFR). The synergistic bioenhancer properties of Gly with Nor and their enhanced ROS generation against MDRSA are reported for the first time in this study. Severe oxidative stress caused membrane damage, DNA fragmentation, transcriptional changes, and bacterial cell death. We strongly believe this could be a potential measure against rapidly evolving MDRSA.","PeriodicalId":131152,"journal":{"name":"Drugs and Drug Candidates","volume":"30 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116601630","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}

引用次数: 0

Design, Synthesis and In Vitro Studies of 3-Amidocoumarins as Novel Antibiofilm Agents 新型抗菌剂3-氨基香豆素的设计、合成及体外研究

Drugs and Drug Candidates Pub Date : 2023-04-21 DOI: 10.3390/ddc2020015

R. Sharma, Vineeta Singh, Vaishali Raghuvanshi, D. Katiyar

{"title":"Design, Synthesis and In Vitro Studies of 3-Amidocoumarins as Novel Antibiofilm Agents","authors":"R. Sharma, Vineeta Singh, Vaishali Raghuvanshi, D. Katiyar","doi":"10.3390/ddc2020015","DOIUrl":"https://doi.org/10.3390/ddc2020015","url":null,"abstract":"Pseudomonas aeruginosa, a life-threatening bacteria listed as a priority pathogen by World Health Organization WHO, is known to cause severe nosocomial infections and fatality in immunocompromised individuals through its quorum sensing (QS) mediated biofilm formation. P. aeruginosa’s antibiotic-resistant biofilms are highly challenging to the existing antibiotic treatment options. There is an urgent clinical need to develop novel alternative therapeutic molecules such as antibiofilm and antiquorum sensing agents to counter the emergence of an unprecedented pace of antibiotic resistance of pathogens. In this context, a library of seventy 3-amidocoumarin derivatives was designed, and docking studies were performed against the P. aeruginosa LasR receptor using AutoDock 4.0. Based on docking results, a final series of sixteen 3-amidocoumarin derivatives (4a–p) were synthesized and evaluated for antibiofilm activity in vitro. Eight compounds significantly inhibited the formation of P. aeruginosa PAO1 biofilm. Compounds 4f, 4l and 4o showed maximum % inhibition in antibiotic-resistant P. aeruginosa PAO1 biofilm formation in the range of 80% to 86%. Further, the structure–activity relationship (SAR) studies revealed that the presence of electron-donating and bromo substituents at benzamido and coumarin moieties, respectively, effectively enhances the antibiofilm activity. In addition, the binding interactions between the synthesized compounds and active sites of the LasR QS receptor (Protein Data Bank Code: 2uv0) in P. aeruginosa were also investigated by molecular docking. The high binding affinities indicate that these compounds might be suitable for development into potent inhibitors of QS and biofilm disruptors.","PeriodicalId":131152,"journal":{"name":"Drugs and Drug Candidates","volume":"24 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133645500","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}

引用次数: 0

Therapeutic Perspectives of Metal Nanoformulations 金属纳米制剂的治疗前景

Drugs and Drug Candidates Pub Date : 2023-04-13 DOI: 10.3390/ddc2020014

Tawhida Islam, M. Rahaman, Md Nayem Mia, I. Ara, M. Islam, Thoufiqul Alam Riaz, A. C. Araújo, João Marcos Ferreira de Lima Silva, Bruna Caroline Gonçalves Vasconcelos de Lacerda, Edlane Martins de Andrade, Muhammad Ali Khan, H. Coutinho, Zakir Husain, M. T. Islam

{"title":"Therapeutic Perspectives of Metal Nanoformulations","authors":"Tawhida Islam, M. Rahaman, Md Nayem Mia, I. Ara, M. Islam, Thoufiqul Alam Riaz, A. C. Araújo, João Marcos Ferreira de Lima Silva, Bruna Caroline Gonçalves Vasconcelos de Lacerda, Edlane Martins de Andrade, Muhammad Ali Khan, H. Coutinho, Zakir Husain, M. T. Islam","doi":"10.3390/ddc2020014","DOIUrl":"https://doi.org/10.3390/ddc2020014","url":null,"abstract":"In recent decades, acceptance of nanoparticles (NPs) in therapeutic applications has increased because of their outstanding physicochemical features. By overcoming the drawbacks of conventional therapy, the utilization of metal NPs, metal-oxide, or metal supported nanomaterials have shown to have significant therapeutic applications in medicine. This is proved by a lot of clinical and laboratory investigations that show improved treatment outcomes, site-specific drug delivery, and fewer side effects compared to traditional medicine. The metal NPs interaction with living cells (animal and plant) showed many ways to develop therapeutic models with the NPs. Despite all of the advancements that science has achieved, there is still a need to find out their performance for long-term use to solve modern challenges. In this regard, the present documentation reviews some potential metals, including silver (Ag), gold (Au), zinc (Zn), copper (Cu), iron (Fe), and nickel (Ni) NPs, as therapeutic agents in various areas such as anticancer, antimicrobial, antidiabetic, and applicable for the treatment of many other diseases. Depending on the outstanding ongoing research and practical trials, metal-based NPs can be considered the hope of prospective modern therapeutic areas.","PeriodicalId":131152,"journal":{"name":"Drugs and Drug Candidates","volume":"194 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133681005","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}

引用次数: 2

A Systematic Review of Molecular Pathway Analysis of Drugs for Potential Use in Liver Cancer Treatment 肝癌治疗药物分子通路分析的系统综述

Drugs and Drug Candidates Pub Date : 2023-04-03 DOI: 10.3390/ddc2020013

Ruchi Jakhmola Mani, Mridul Anand, Kritie Agarwal, Avi Tiwari, Qazi Amanur Rahman Hashmi, Tumul Vikram Singh, P. Nongdam, D. Katare, Angamba Meetei Potshangabam

{"title":"A Systematic Review of Molecular Pathway Analysis of Drugs for Potential Use in Liver Cancer Treatment","authors":"Ruchi Jakhmola Mani, Mridul Anand, Kritie Agarwal, Avi Tiwari, Qazi Amanur Rahman Hashmi, Tumul Vikram Singh, P. Nongdam, D. Katare, Angamba Meetei Potshangabam","doi":"10.3390/ddc2020013","DOIUrl":"https://doi.org/10.3390/ddc2020013","url":null,"abstract":"Liver cancer is a high mortality cancer, and its increasing prevalence is a concern worldwide. Current treatment modalities for liver cancer include chemotherapy and immunotherapy. These therapies provide symptomatic relief and help prolong the lives of patients but are not an absolute cure. In this paper we have explored an alternative approach, drug repurposing, to identify drugs for treating liver cancer. Databases like PubMed, ScienceDirect, and JSTOR were used for literature mining, and the PRISMA 2020 systemic review guidelines were followed to identify drugs that have been trialed for repurposing in liver cancer. The protein receptors and target protein classes of all the drugs were identified using the Swiss Target Prediction tool. Further, the biological interactions and pathways followed by the drugs were studied via protein interaction networks using Cytoscape. Molecular pathways such as Bile acid receptor activity, Inosine-5′-monophosphate (IMP) dehydrogenase activity, JUN kinase activity, Nitric-oxide synthase activity, and Mitogen-activated protein (MAP) kinase activity were observed to be influenced by these drugs. The fact that the genes targeted by these repurposed drugs are common with the differentially expressed genes in liver cancer is an excellent starting point to verify the current hypothesis.","PeriodicalId":131152,"journal":{"name":"Drugs and Drug Candidates","volume":"13 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130719396","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}

引用次数: 0

Optimizing Protein Production in Therapeutic Phages against a Bacterial Pathogen, Mycobacterium abscessus 优化治疗性噬菌体对细菌病原体脓肿分枝杆菌的蛋白质生产

Drugs and Drug Candidates Pub Date : 2023-03-21 DOI: 10.3390/ddc2010012

X. Xia

{"title":"Optimizing Protein Production in Therapeutic Phages against a Bacterial Pathogen, Mycobacterium abscessus","authors":"X. Xia","doi":"10.3390/ddc2010012","DOIUrl":"https://doi.org/10.3390/ddc2010012","url":null,"abstract":"Therapeutic phages against pathogenic bacteria should kill the bacteria efficiently before the latter evolve resistance against the phages. While many factors contribute to phage efficiency in killing bacteria, such as phage attachment to host, delivery of phage genome into the host, phage mechanisms against host defense, phage biosynthesis rate, and phage life cycle, this paper focuses only on the optimization of phage mRNA for efficient translation. Phage mRNA may not be adapted to its host translation machinery for three reasons: (1) mutation disrupting adaptation, (2) a recent host switch leaving no time for adaptation, and (3) multiple hosts with different translation machineries so that adaptation to one host implies suboptimal adaptation to another host. It is therefore important to optimize phage mRNAs in therapeutic phages. Theoretical and practical principles based on many experiments were developed and applied to phages engineered against a drug-resistant Mycobacterium abscessus that infected a young cystic fibrosis patient. I provide a detailed genomic evaluation of the three therapeutic phages with respect to translation initiation, elongation, and termination, by making use of both experimental results and highly expressed genes in the host. For optimizing phage genes against M. abscessus, the start codon should be AUG. The DtoStart distance from base-pairing between the Shine-Dalgarno (SD) sequence and the anti-SD sequence should be 14–16. The stop codon should be UAA. If UAG or UGA is used as a stop codon, they should be followed by nucleotide U. Start codon, SD, or stop codon should not be embedded in a secondary structure that may obscure the signals and interfere with their decoding. The optimization framework should be generally applicable to developing therapeutic phages against bacterial pathogens.","PeriodicalId":131152,"journal":{"name":"Drugs and Drug Candidates","volume":"61 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126392824","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}

引用次数: 2