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Nature Reviews. Drug Discovery Feb 2015Natural products have been a rich source of compounds for drug discovery. However, their use has diminished in the past two decades, in part because of technical... (Review)
Review
Natural products have been a rich source of compounds for drug discovery. However, their use has diminished in the past two decades, in part because of technical barriers to screening natural products in high-throughput assays against molecular targets. Here, we review strategies for natural product screening that harness the recent technical advances that have reduced these barriers. We also assess the use of genomic and metabolomic approaches to augment traditional methods of studying natural products, and highlight recent examples of natural products in antimicrobial drug discovery and as inhibitors of protein-protein interactions. The growing appreciation of functional assays and phenotypic screens may further contribute to a revival of interest in natural products for drug discovery.
Topics: Animals; Anti-Infective Agents; Biodiversity; Biological Products; Clinical Trials as Topic; Drug Discovery; Drug Evaluation, Preclinical; Genomics; Humans; Molecular Structure
PubMed: 25614221
DOI: 10.1038/nrd4510 -
Clinical Microbiology Reviews Apr 2015Substandard/counterfeit antimicrobial drugs are a growing global problem. The most common substandard/counterfeit antimicrobials include beta-lactams (among antibiotics)... (Review)
Review
Substandard/counterfeit antimicrobial drugs are a growing global problem. The most common substandard/counterfeit antimicrobials include beta-lactams (among antibiotics) and chloroquine and artemisin derivatives (among antimalarials). The most common type of substandard/counterfeit antimicrobial drugs have a reduced amount of the active drug, and the majority of them are manufactured in Southeast Asia and Africa. Counterfeit antimicrobial drugs may cause increased mortality and morbidity and pose a danger to patients. Here we review the literature with regard to the issue of substandard/counterfeit antimicrobials and describe the prevalence of this problem, the different types of substandard/counterfeit antimicrobial drugs, and the consequences for the individuals and global public health. Local, national, and international initiatives are required to combat this very important public health issue.
Topics: Anti-Infective Agents; Counterfeit Drugs; International Cooperation; Public Health
PubMed: 25788516
DOI: 10.1128/CMR.00072-14 -
International Journal of Infectious... Oct 2011There is an urgent need to develop vaginal microbicides to empower women to better control their own sexual life and to protect themselves against HIV and other sexually... (Review)
Review
There is an urgent need to develop vaginal microbicides to empower women to better control their own sexual life and to protect themselves against HIV and other sexually transmitted infections (STIs). Prevention of STIs with its 330 million cases a year would have a great global health impact. Because of their anatomy, women are up to 8 times more susceptible than men to STIs including HIV. Women who can't negotiate condom use with their male partners have no means of protecting themselves from these infections. In the last few years, especially after the recent failures of several microbicides in Phase III trials, there was increasing pressure from those favoring the use of a more targeted approach to introduce marketed antiretroviral drugs (ARVs) into microbicides. This Pre-Exposure Prophylaxis (PrEP) concept which targets only HIV using specific ARVs contrasts with the primary approach of broad spectrum microbicides which aimed at offering universal protection against several sexually transmitted pathogens. However, before using ARVs as PrEP for HIV prevention, there are still many important issues to consider. In this article, we compare both strategies, while reviewing the last 15 years of microbicide research and its future.
Topics: Anti-Infective Agents; Anti-Retroviral Agents; Antibiotic Prophylaxis; Female; HIV Infections; Humans; Male; Sexually Transmitted Diseases; Treatment Failure
PubMed: 21705253
DOI: 10.1016/j.ijid.2011.05.001 -
Drug Delivery and Translational Research Dec 2017Sexual intercourse (vaginal and anal) is the predominant mode of human immunodeficiency virus (HIV) transmission. Topical microbicides used in an on-demand format (i.e.,... (Review)
Review
Sexual intercourse (vaginal and anal) is the predominant mode of human immunodeficiency virus (HIV) transmission. Topical microbicides used in an on-demand format (i.e., immediately before or after sex) can be part of an effective tool kit utilized to prevent sexual transmission of HIV. The effectiveness of prevention products is positively correlated with adherence, which is likely to depend on user acceptability of the product. The development of an efficacious and acceptable product is therefore paramount for the success of an on-demand product. Acceptability of on-demand products (e.g., gels, films, and tablets) and their attributes is influenced by a multitude of user-specific factors that span behavioral, lifestyle, socio-economic, and cultural aspects. In addition, physicochemical properties of the drug, anatomical and physiological aspects of anorectal and vaginal compartments, issues relating to large-scale production, and cost can impact product development. These factors together with user preferences determine the design space of an effective, acceptable, and feasible on-demand product. In this review, we summarize the interacting factors that together determine product choice and its target product profile.
Topics: Administration, Rectal; Administration, Topical; Anti-Infective Agents; Clinical Trials as Topic; Female; HIV Infections; Humans; Male; Patient Compliance; Patient Preference; Sexual Behavior; Vaginal Creams, Foams, and Jellies
PubMed: 28589452
DOI: 10.1007/s13346-017-0385-4 -
Journal of the International AIDS... Apr 2013After two decades of microbicide clinical trials it remains uncertain if vaginally- delivered products will be clearly shown to reduce the risk of HIV infection in women... (Review)
Review
After two decades of microbicide clinical trials it remains uncertain if vaginally- delivered products will be clearly shown to reduce the risk of HIV infection in women and girls. Furthermore, a microbicide product with demonstrated clinical efficacy must be used correctly and consistently if it is to prevent infection. Information on adherence that can be gleaned from microbicide trials is relevant for future microbicide safety and efficacy trials, pre-licensure implementation trials, Phase IV post-marketing research, and microbicide introduction and delivery. Drawing primarily from data and experience that has emerged from the large-scale microbicide efficacy trials completed to-date, the paper identifies six broad areas of adherence lessons learned: (1) Adherence measurement in clinical trials, (2) Comprehension of use instructions/Instructions for use, (3) Unknown efficacy and its effect on adherence/Messages regarding effectiveness, (4) Partner influence on use, (5) Retention and continuation and (6) Generalizability of trial participants' adherence behavior. Each is discussed, with examples provided from microbicide trials. For each of these adherence topics, recommendations are provided for using trial findings to prepare for future microbicide safety and efficacy trials, Phase IV post-marketing research, and microbicide introduction and delivery programs.
Topics: Administration, Intravaginal; Anti-Infective Agents; Clinical Trials as Topic; Female; HIV Infections; Humans; Male; Medication Adherence
PubMed: 23561044
DOI: 10.7448/IAS.16.1.18505 -
Current HIV Research Jan 2012Despite the identification of HIV-1 as the etiological agent responsible for AIDS nearly 30 years ago, a sterilizing vaccine capable of preventing transmission of the... (Review)
Review
Despite the identification of HIV-1 as the etiological agent responsible for AIDS nearly 30 years ago, a sterilizing vaccine capable of preventing transmission of the virus remains elusive. In response to struggles on the vaccine development front, significant effort has been devoted to preventing the transmission of HIV with alternative products, technologies, and strategies. One of the early alternative HIV prevention strategies was microbicides, which are topical products that can be used to prevent sexual transmission of HIV either vaginally or rectally. First generation microbicide products were designed to be simple gel formulations comprised of readily available active agents that were inexpensive and broadly active (i.e., non-specific). Unfortunately, despite the clinical investigation of multiple product concepts satisfying these requirements, none were shown to be efficacious in pivotal trials. More recently, microbicide and oral prevention strategies involving highly specific and potent anti-retroviral (ARV) drugs have shown to be efficacious in trials. Although building on these successes continues, these products have a number of issues including potential toxicity with long term use, selection of HIV resistance, and cost. Further, all of the original justifications for non-specific microbicide products remain valid. This review provides a brief history of non-specific microbicide development, outlines the evolution to, and limitations of, ARV based microbicides, and summarizes the current activity on non-specific microbicide product development.
Topics: Administration, Topical; Anti-Infective Agents, Local; Anti-Retroviral Agents; Clinical Trials as Topic; Drug Evaluation, Preclinical; HIV Infections; Humans; Surface-Active Agents
PubMed: 22264041
DOI: 10.2174/157016212799304625 -
Theranostics 2020Carbon dots (CDots) have emerged to represent a highly promising new platform for visible/natural light-activated microbicidal agents. In this article, the syntheses,... (Review)
Review
Carbon dots (CDots) have emerged to represent a highly promising new platform for visible/natural light-activated microbicidal agents. In this article, the syntheses, structures, and properties of CDots are highlighted, representative studies on their activities against bacteria, fungi, and viruses reviewed, and the related mechanistic insights discussed. Also highlighted and discussed are the excellent opportunities for potentially extremely broad applications of this new platform, including theranostics uses.
Topics: Anti-Infective Agents; Bacteria; Carbon; Drug Resistance, Microbial; Nanostructures; Quantum Dots
PubMed: 31903144
DOI: 10.7150/thno.39863 -
International Journal of Molecular... Jan 2023Surface contamination by microorganisms such as viruses and bacteria may simultaneously aggravate the biofouling of surfaces and infection of wounds and promote... (Review)
Review
Surface contamination by microorganisms such as viruses and bacteria may simultaneously aggravate the biofouling of surfaces and infection of wounds and promote cross-species transmission and the rapid evolution of microbes in emerging diseases. In addition, natural surface structures with unique anti-biofouling properties may be used as guide templates for the development of functional antimicrobial surfaces. Further, these structure-related antimicrobial surfaces can be categorized into microbicidal and anti-biofouling surfaces. This review introduces the recent advances in the development of microbicidal and anti-biofouling surfaces inspired by natural structures and discusses the related antimicrobial mechanisms, surface topography design, material application, manufacturing techniques, and antimicrobial efficiencies.
Topics: Anti-Infective Agents; Biofouling; Bacteria; Surface Properties
PubMed: 36674860
DOI: 10.3390/ijms24021348 -
Toxins Nov 2018Antimicrobial peptides (AMPs) are crucial effectors of the innate immune system. They provide the first line of defense against a variety of pathogens. AMPs display... (Review)
Review
Antimicrobial peptides (AMPs) are crucial effectors of the innate immune system. They provide the first line of defense against a variety of pathogens. AMPs display synergistic effects with conventional antibiotics, and thus present the potential for combined therapies. Insects are extremely resistant to bacterial infections. Insect AMPs are cationic and comprise less than 100 amino acids. These insect peptides exhibit an antimicrobial effect by disrupting the microbial membrane and do not easily allow microbes to develop drug resistance. Currently, membrane mechanisms underlying the antimicrobial effects of AMPs are proposed by different modes: the barrel-stave mode, toroidal-pore, carpet, and disordered toroidal-pore are the typical modes. Positive charge quantity, hydrophobic property and the secondary structure of the peptide are important for the antibacterial activity of AMPs. At present, several structural families of AMPs from insects are known (defensins, cecropins, drosocins, attacins, diptericins, ponericins, metchnikowins, and melittin), but new AMPs are frequently discovered. We reviewed the biological effects of the major insect AMPs. This review will provide further information that facilitates the study of insect AMPs and shed some light on novel microbicides.
Topics: Amino Acid Sequence; Animals; Anti-Infective Agents; Bacterial Infections; Insecta
PubMed: 30413046
DOI: 10.3390/toxins10110461 -
Virology Oct 2016The majority of HIV-1 infections occur via sexual intercourse. Women are the most affected by the epidemic, particularly in developing countries, due to their... (Review)
Review
The majority of HIV-1 infections occur via sexual intercourse. Women are the most affected by the epidemic, particularly in developing countries, due to their socio-economic dependence on men and the fact that they are often victims of gender based sexual violence. Despite significant efforts that resulted in the reduction of infection rates in some countries, there is still need for effective prevention methods against the virus. One of these methods for preventing sexual transmission in women is the use of microbicides. In this review we provide a summary of the progress made toward the discovery of affordable and effective HIV-1 microbicides and suggest future directions. We show that there is a wide range of compounds that have been proposed as potential microbicides. Although most of them have so far failed to show protection in humans, there are many promising ones currently in pre-clinical studies and in clinical trials.
Topics: Animals; Anti-Infective Agents; Drug Carriers; Drug Delivery Systems; Drug Discovery; Female; Genitalia, Female; HIV Infections; HIV-1; Humans; Male; Mucous Membrane; Sexually Transmitted Diseases, Viral
PubMed: 27429040
DOI: 10.1016/j.virol.2016.07.004