USE OF SMARTPHONES APPLICATIONS FOR PARTNERING AMONG MSM
W Eric
Columbia University Health Sciencescity: New York country: United States (us)
Grant 1R21MH096639-01 from National Institute Of Mental Health
Abstract: Smartphone technologies (i.e., cellular telephones, such as the iPhone, Android phones, and newer generation Blackberry phones), have provided a new venue for sexual partnering among men who have sex with men (MSM). Indeed, there are a rapidly growing number of smartphone applications designed to facilitate sexual partnering among MSM. Although all smartphones can access Internet sites for sexual partnering, smartphone applications designed for sexual partnering go a step further by utilizing the Global Positioning System (GPS) technology built into smartphones to help MSM identify potential partners who are geographically closest to their current position. As such, these technologies may have accelerated the rate with which men can meet and connect with sexual partners over that of the traditional Internet. Furthermore, given the expediency with which men are able to arrange sexual encounters using these applications, there is cause to question if, when, and how sexual negotiation and serostatus disclosure occurs. The overall study goal is to understand how sexual risk behaviors among MSM may be facilitated by the nature of GPS-enabled smartphone applications, the way they are used, and the process by which sexual partnering occurs via smartphone applications. We will conduct in-depth qualitative interviews with 60 MSM (20 African American, 20 Latino, 20 White; 25% of whom are HIV-positive) who have utilized smartphone applications to meet sexual partners in the past 3 months. For each of the aims below, while our focus is on smartphone use, we will also collect information on their use of Internet partnering sites to use as a context for comparison and identify what might be unique to smartphone usage. The study aims are 1. Examine how and why smartphone applications are used for sexual partnering, the situations and locations in which they are used, in order to gain insights into how these use patterns might contribute to sexual risk behaviors. 2. Investigate the process by which MSM use smartphone applications to find sexual partners (i.e., who they look for, how they present themselves, how they communicate, extent of safer sex negotiation,and disclosure) to gain insights into how this process may contribute to sexual risk behaviors. 3. Investigate the sexual and emotional states (e.g., more/less urgency, arousal, impulsivity) that MSM experience when seeking or meeting sexual partners using smartphone applications and gain insights into how these states may contribute to sexual risk behaviors. 4. Examine the perceived need and acceptability of a smartphone delivered intervention and assess what MSM perceive as needed components for a smartphone-based sexual risk reduction intervention. Smartphone technologies (such as the iPhone, Android phones, and newer generation Blackberry phones), have provided a new venue for sexual partnering among men who have sex with men (MSM). Smartphone applications designed for sexual partnering utilize GPS technology built into smartphones to help MSM identify potential partners who are geographically closest to their current position. As such, these technologies may have accelerated the rate with which men can meet and connect with sexual partners over that of the traditional Internet. To understand how sexual risk behaviors among MSM may be facilitated by the nature of GPS-enabled smartphone applications, we will conduct in-depth qualitative interviews with 60 MSM (20 African American, 20 Latino, 20 White; 25% of whom are HIV-positive) who have utilized smartphone applications to meet sexual partners in the past 3 months
Keywords: African American; Age; Arousal; Attention; base; Cellular Phone; Computer software; Data Collection; design; digital; Disclosure; Effectiveness; Emotional; Ethnicity aspects; experience; Exploratory/Developmental Grant; Explosion; foot; Funding; Gays; Gender; Generations; Glosso-Sterandryl; Goals; Hispanics; HIV; HIV Infections; HIV Seropositivity; HIV/STD; Home environment; Impulsivity; Individual; innovation; insight; Internet; Intervention; Interview; Latino; Lead; Location; Market Research; Marketing; Mediation; meetings; men; men who have sex with men; Methods; Nature; new technology; New York City; Participant; Pattern; Positioning Attribute; Process; Race; Research; Research Design; Research Project Grants; Risk Reduction; Role; safer sex; sex; sex risk; sexual encounter; Sexual Partners; Site; Speed (motion); System; Technology; Telephone; Text; Time; web site; Work
Relevance: Smartphone technologies (such as the iPhone, Android phones, and newer generation Blackberry phones), have provided a new venue for sexual partnering among men who have sex with men (MSM). Smartphone applications designed for sexual partnering utilize GPS technology built into smartphones to help MSM identify potential partners who are geographically closest to their current position. As such, these technologies may have accelerated the rate with which men can meet and connect with sexual partners over that of the traditional Internet. To understand how sexual risk behaviors among MSM may be facilitated by the nature of GPS-enabled smartphone applications, we will conduct in-depth qualitative interviews with 60 MSM (20 African American, 20 Latino, 20 White; 25% of whom are HIV-positive) who have utilized smartphone applications to meet sexual partners in the past 3 months
Project start date: 2012-01-16
Project end date: 2013-12-31
Budget start date: 16-JAN-2012
Budget end date: 31-DEC-2012
1R21MH096639-01 (2012): $240000
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to W Eric
DEVELOPMENT OF NOVEL SMALL MOLECULE FLAVIVIRUS INHIBITORS
W Eric, Professor
Virogenomics, Inc.city: Tigard country: United States (us)
Grant 5R41AI078582-02 from National Institute Of Allergy And Infectious Diseases
Abstract: We have identified TYT-1 as a novel sultam thiourea inhibitor of West Nile virus (WNV) replication. The compound has a 50% effective concentration (EC50) of 0.7 micromolar and a 50% cytotoxic concentration (CC50) of >70 micromolar, yielding a therapeutic (selectivity) index of >100. We have demonstrated that TYT-1 protects animals from the lethality of WNV infection, that the compound reduces viral RNA levels over a hundred-fold in infected cells, and that TYT-1 analogues inhibit replication of related flaviviruses such as the Japanese encephalitis virus (JEV) and the category A biodefense pathogen Dengue virus (DENV). The development of TYT-1-based antivirals will provide a new approach to the treatment of flavivirus infections, and will complement vaccine approaches. Because very few sultam thioureas have been described, our work also will establish a foundation for their efficient preparation, and for their use in biomedical applications. To achieve these goals, we propose phase I studies to perfect sultam thiourea synthesis methodology, to assess analogue inhibition efficacy, to characterize mechanisms of inhibition, and to evaluate compound toxicity and metabolism in animals. Our specific aims are as follows 1.Synthesis and evaluation of sultam thiourea analogues Methods for the synthesis of TYT-1 and analogues will be optimized, and compound cellular toxicities and antiviral effects against flavivirus strains will be quantitated. These studies will perfect pathways for analogue preparation, and determine chemical and viral requirements for inhibition. 2. Characterization of the mechanism of compound inhibition The mechanism of TYT-1 inhibition of WNV will be characterized. Examination of compound effects on wild type infections and replicon expression will help delineate inhibitor activities, and assays on viral protein activities will help define inhibition mechanisms. Analysis of putative drug resistant mutants will help assess whether resistance is acquired at a fitness cost to the virus, and will identify viral genes targeted by inhibitors. Our results will establish a mode of antiviral action, and ways to optimize inhibitor activities. 3. Examination of TYT-1 toxicity and metabolism To examine the safety of sultam thioureas, toxicology studies on TYT-1 will be performed in mice. To gain an understanding of how these unique compounds are metabolized, pharmacokinetic studies will be performed in vitro and in vivo. These studies will serve as an essential basis for development of sultam thioureas as antivirals, and for other possible therapeutic purposes investigations are designed to develop new antivirals against the human pathogens West Nile virus, Japanese encephalitis virus, and Dengue virus. We have identified a novel class of flavivirus inhibitor, representatives of which inhibit West Nile virus (WNV) and Japanese encephalitis virus (JEV) replication in cell culture, and protect animals from WNV lethality. We propose to perfect compound synthesis methodology, to assess analogue inhibition efficacy against flavivirus strains, to characterize mechanisms of inhibition, and to evaluate compound toxicity and metabolism in animals. Our results will lead to the development of new antivirals, and an understanding of how they work
Keywords: analog; Animals; Antiviral Agents; Antiviral Drugs; Antivirals; Arbovirus, Group B; Assay; base; Bioassay; biodefense; Biologic Assays; Biological Assay; Breakbone Fever Virus; Categories; Cell Culture Techniques; Cells; Chemicals; Complement; Complement Proteins; cost; cytotoxic; Dengue Virus; design; designing; Development; Drug Kinetics; Drug resistance; drug resistant; Egypt 101 virus; Encephalitis Viruses, Japanese; Evaluation; fitness; Flavivirus; Flavivirus Infections; Foundations; Gene Targeting; Goals; heavy metal lead; heavy metal Pb; Human; Human, General; In Vitro; in vivo; indexing; Infection; inhibitor; inhibitor/antagonist; Intermediary Metabolism; Investigation; Japanese B Encephalitis Virus; Japanese encephalitis virus; Japanese encephalitis virus group; Japanese Encephalitis Viruses; Lead; Mammals, Mice; Man (Taxonomy); Man, Modern; Metabolic Processes; Metabolism; METBL; Method LOINC Axis 6; Methodology; Methods; Mice; Murine; Mus; mutant; new approaches; novel; novel approaches; novel strategies; novel strategy; pathogen; pathway; Pathway interactions; Pb element; Pharmacokinetics; phase 1 study; Preparation; public health relevance; Replication Unit; Replicon; Resistance; resistance to Drug; resistant; resistant to Drug; RNA, Viral; Safety; small molecule; Targetings, Gene; Therapeutic; Thiourea; thiourea analog; Toxic effect; Toxicities; Toxicology; Vaccines; Viral; Viral Diseases; Viral Gene Products; Viral Gene Proteins; Viral Genes; viral infection; Viral Proteins; viral RNA; Virus; Virus Diseases; virus infection; virus multiplication; virus protein; Virus Replication; virus RNA; Viruses, General; West Nile; West Nile virus; WNV; Work
Relevance: We have identified a novel class of flavivirus inhibitor, representatives of which inhibit West Nile virus (WNV) and Japanese encephalitis virus (JEV) replication in cell culture, and protect animals from WNV lethality. We propose to perfect compound synthesis methodology, to assess analogue inhibition efficacy against flavivirus strains, to characterize mechanisms of inhibition, and to evaluate compound toxicity and metabolism in animals. Our results will lead to the development of new antivirals, and an understanding of how they work
Project start date: 2009-03-01
Project end date: 2012-02-28
Budget start date: 1-MAR-2010
Budget end date: 28-FEB-2012
PFA/PA: PA-08-051
5R41AI078582-02 (2010): $301727
SMALL MOLECULE FLAVIVIRUS INHIBITORS
W Eric, Professor
Oregon Health And Science Universitycity: Portland country: United States (us)
Abstract: We have identified novel small compound inhibitors of flavivims replication. Our most potent compound has a 50% effective concentration (EC50) of 0.7 micromolar and a 50% cytotoxic concentration (CC50) of >70 micromolar, yielding a therapeutic (selectivity) index of >100. We have demonstrated that the compound protects animals from the lethality of WNV infection and reduces viral RNA levels over a hundred-fold in infected cells; and that analogues inhibit replication of related flaviviruses such as the select agent Japanese encephalitis virus (JEV) and the category A biodefense pathogen Dengue virus (DENV). The development of our small molecule antivirals will provide a new approach to the treatment of flavivirus infections, and will complement vaccine approaches. Moreover, because very few putative flavivirus inhibitors have been described, our work is essential to establish a foundation for understanding structure-activity relationships and how these compounds influence host cell functions and innate immunity. To achieve these goals, we propose to analyze the antiviral activities and potential toxicities of small compound analogues related to our inhibitors; to characterize their antiviral mechanisms; and to examine their effects on host cells. Our specific aims are as follows 1 .Analysis of small molecule anti-flavivirus activities Small libraries of flavivirus inhibitors and related analogues will be prepared, and compound cellular toxicities and antiviral effects against flavivirus strains will be quantitated. These studies will determine chemical and strain requirements for virus inhibition. 2. Characterization of the mechanisms of compound inhibition The mechanisms of viral inhibition will be characterized. Examination of compound effects on wild type infections and replicon expression will help delineate inhibitor activities, and assays on viral protein activities will help define inhibition mechanisms. Analysis of putative drug-resistant mutants will help assess whether resistance is acquired at a fitness cost to the virus, and will identify genes targeted by inhibitors. Our results will establish a mode of antiviral action, and ways to optimize inhibitor activities. 3. Examination of inhibitor effects on host cells Although our most effective flavivirus inhibitors are non-toxic, their specific effects on host cells are almost completely unknown. To fill this gap, we will monitor compound effects on infected and uninfected cells. These results will provide crucial data as to how our novel class of flavivirus inhibitors influence cellular expression profiles and innate immune response mechanisms
Keywords: analog; Animals; Antiviral Agents; Antiviral Drugs; Antivirals; Arbovirus, Group B; Assay; Bioassay; biodefense; Biologic Assays; Biological Assay; Breakbone Fever Virus; Categories; Cell Function; Cell physiology; Cell Process; Cells; Cellular Function; Cellular Physiology; Cellular Process; chemical structure function; Chemicals; Complement; Complement Proteins; cost; cytotoxic; Data; Dengue Virus; Development; Drug resistance; drug resistant; Egypt 101 virus; Encephalitis Viruses, Japanese; Expression Profiling; Expression Signature; fitness; Flavivirus; Flavivirus Infections; Fostering; Foundations; Gene Targeting; Goals; host response; Immune response; Immunity, Innate; Immunity, Native; Immunity, Natural; Immunity, Non-Specific; immunoresponse; indexing; Infection; inhibitor; inhibitor/antagonist; Investigation; Japanese B Encephalitis Virus; Japanese encephalitis virus; Japanese encephalitis virus group; Japanese Encephalitis Viruses; Libraries; molecuar profile; Molecular Fingerprinting; Molecular Profiling; molecular signature; Monitor; mutant; Natural Immunity; new approaches; new therapeutics; next generation therapeutics; novel; novel approaches; novel strategies; novel strategy; novel therapeutics; Pacific Northwest; pathogen; Replication Unit; Replicon; Resistance; resistance to Drug; resistant; resistant to Drug; RNA, Viral; small molecule; structure function relationship; Structure-Activity Relationship; Subcellular Process; Targetings, Gene; Therapeutic; Toxic effect; Toxicities; Vaccines; Viral; Viral Gene Products; Viral Gene Proteins; Viral Proteins; viral RNA; Virus; virus protein; virus RNA; Viruses, General; West Nile; West Nile virus; WNV; Work
Relevance: Our goal is to develop new therapeutics against flavivirus infections. Through these investigations, we will optimize activities of compounds that inhibit West Nile virus, Japanese encephalitis virus, and Dengue virus; and will determine the effects of these inhibitors on normal cellular processes so that the can be employed safely and effectively
Budget start date: 1-MAR-2011
Budget end date: 29-FEB-2012
5U54AI081680-03_6284 (2011): $260046
RAPID SCREENING AND DEREPLICATION OF MARINE SYMBIOTIC NATURAL PRODUCTS
W Eric, Assistant Professor
University Of Utahcity: Salt Lake City country: United States (us)
Grant 5R01GM092009-02 from National Institute Of General Medical Sciences
Abstract: The majority of pharmaceuticals are derived from natural products either directly or indirectly. However, the pipeline to new natural products has been drying up over the last decades as the technologies became less amenable to high- throughput screening and as finding new natural products became increasingly difficult. Substantial progress has been made in these areas by numerous labs, but there are still gaps in technology and in basic understanding of natural product sources. In this project, we will provide new methods and data to help fill these remaining gaps. In addition, we will build natural product compound libraries for screening at NIH and at the University of Wisconsin. The new methods include more rapid, automated, and integrated techniques for extraction, purification, and dereplication of natural products. Basic studies of natural product sources using marine symbiotic bacteria are aimed at answering questions about the most fruitful places to find new natural product producers and about methods to obtain these promising bacteria. These biological and chemical studies are synergistic and will provide the first large, ordered set of data linking cultivated symbiotic bacteria to chemistry in whole animals. The resulting methods are designed to be widely useful in multiple labs and to help in the development of broadly shared platforms for dereplication. The resulting libraries of natural products will be used in a variety of screens at established, high-throughput centers at NIH and U. Wisconsin. We will pursue promising leads as potential new pharmaceuticals. We will develop new methods for the rapid discovery of bioactive natural products and provide new data about sources of natural products that enable drug discovery. We will also provide libraries of natural products for screening. These results will have a large impact on natural products sciences because of new methods and knowledge. The human health impact will result from these new methods and potentially from new therapeutic small molecules discovered in the course of the project
Keywords: Actinobacteria class; Animals; Area; ascidian; Bacteria; Biological; Biological Factors; Chemicals; Chemistry; Clinical; Collaborations; Communities; Data; Data Set; Databases; design; Development; drug discovery; Equipment; experience; Florida; Goals; Health; high throughput screening; Human; Individual; interest; Island; Knowledge; Libraries; Link; Location; marine natural product; marine organism; Marines; Mass Spectrum Analysis; Methods; novel; novel therapeutics; Outcome; Pharmacologic Substance; Prevalence; Procedures; Process; Property; Protocols documentation; public health relevance; Publications; rapid technique; Research Personnel; Role; scaffold; Science; Screening procedure; small molecule; Soil; Source; Speed (motion); Structure; Symbiosis; Techniques; Technology; Therapeutic; tool; United States; United States National Institutes of Health; Universities; Utah; Water; Wisconsin
Relevance: We will develop new methods for the rapid discovery of bioactive natural products and provide new data about sources of natural products that enable drug discovery. We will also provide libraries of natural products for screening. These results will have a large impact on natural products sciences because of new methods and knowledge. The human health impact will result from these new methods and potentially from new therapeutic small molecules discovered in the course of the project
Project start date: 2010-08-15
Project end date: 2013-05-31
Budget start date: 1-JUN-2011
Budget end date: 31-MAY-2012
PFA/PA: RFA-RM-09-005
5R01GM092009-02 (2011): $368879
DEVELOPMENT OF A HIGH THROUGHPUT HIV ASSEMBLY SCREEN
W Eric, Professor
Oregon Health And Science Universitycity: Portland country: United States (us)
Grant 5R01AI071798-04 from National Institute Of Allergy And Infectious Diseases
Abstract: Our proposal responds to the NIH program announcement "Development of assays for high throughput drug screening," which has the goal of offering public sector researchers opportunities to employ high throughput chemical screening (HTS) methods. The announcement asks applicants to propose development plans sufficient to show assay reproducibility; to test the assay with a small compound library; and to provide an outline for evaluating the significance of HTS hits. We describe a unique assay designed to identify compounds that inhibit HIV assembly. Our cell-based assay takes advantage of the fact that chimeric proteins can serve as sensitive, efficient, and reproducible reporters for virus assembly with signal-to-noise ratios that should be suitable for HTS. Our investigations will lead to the identification of compounds that inhibit transport, assembly and release of virions from virus-expressing cells. Such inhibitors will provide new HIV antivirals, will help unravel the complicated choreography of HIV assembly, and may reveal ways to block the replication of other pathogenic viruses. Thus, the results of our studies will have general applicability in understanding the HIV life cycle and in stopping virus infections. In keeping with program announcement guidelines, to achieve these goals, our specific aims are as follows 1. Optimization of assembly assays for high throughput screening Assembly assays will be modified to reduce assay-to-assay variability, improve signal-to-noise ratios, increase screening coefficient ratios, and adapt protocols for HTS formats. 2. Assay characterization using small chemical libraries Optimized screening protocols will be employed to test small chemical libraries of diverse compound sets. Test screen data will be evaluated to assess statistical screening parameters, and results will be used to further refine methodologies for HTS. 3. Development of secondary screening procedures Procedures for analysis and prioritization of primary hits will be developed and streamlined. Methods to rule out artifacts, and to discriminate specific assembly steps impacted by candidate inhibitors will be designed and tested. Through these efforts, the prospect of finding novel HIV inhibitors, and elucidating new assembly steps will be realized. Our investigations are directly relevant to public health. We propose to develop a high throughput screen that will identify inhibitors of HIV assembly. Such inhibitors will serve as leads in the design of novel drugs for the treatment of AIDS
Keywords: Acquired Immunodeficiency Syndrome; Antiviral Agents; assay development; base; Biological Assay; Cells; Chemicals; Chimeric Proteins; Data; design; Development; Development Plans; Eligibility Determination; Goals; Guidelines; high throughput screening; HIV; improved; inhibitor/antagonist; Investigation; Lead; Libraries; Life Cycle Stages; Methodology; Methods; Morphologic artifacts; NIH Program Announcements; Noise; novel; Pharmaceutical Preparations; Preclinical Drug Evaluation; Procedures; Protocols documentation; public health medicine (field); public health relevance; Public Sector; Reporter; Reproducibility; Research Personnel; Screening procedure; Signal Transduction; small molecule libraries; Testing; Virion; Virus; Virus Assembly; Virus Diseases
Project start date: 2007-07-01
Project end date: 2012-06-30
Budget start date: 1-JUL-2010
Budget end date: 30-JUN-2012
PFA/PA: PA-04-068
5R01AI071798-04 (2010): $373909
SPECTRO-TEMPORAL PROCESSING IN SPEECH BY NORMAL AND IMPAIRED LISTENERS
W Eric
Ohio State Universitycity: Columbus country: United States (us)
Grant 5R01DC008594-06 from National Institute On Deafness And Other Communication Disorders
Abstract: Despite that speech is often characterized by either spectral or temporal cues, its everyday perception involves the integration of temporal patterns present at different spectral loci. The long-term goals of the proposed research program are to further our understanding of the normal mechanisms employed during the processing of the spectro-temporal patterns in speech, and to characterize limitations that hearing impairment places on these mechanisms. Techniques combining psychoacoustic and speech perception research will be employed to extend a number of recent observations concerning spectro-temporal processing. These examinations will involve both listeners with normal hearing and those with sensorineural hearing impairment. The aims are (1) To establish the spectral resolution employed to process speech (2) To examine the use of temporal information at different rates and spectral frequencies (3) To examine the spectro-temporal processing deficit in hearing impaired listeners The information gained has the ability to further our understanding of normal speech processing. It also has the ability to further our understanding of the impact of hearing impairment by providing a comprehensive examination of the ability to use the fluctuating temporal patterns in speech, and by examining the influence of broadened auditory tuning on the reception of particular speech materials in particular frequency regions
Keywords: Auditory; Auditory system; Complex; Cueing for speech; Cues; density; design; Diagnosis; Disease; Female; Frequencies (time pattern); Goals; Hearing; hearing impairment; improved; Individual; insight; Linguistics; male; Measures; novel; Pattern; Perception; Physiological; Procedures; Process; programs; Property; Psychoacoustics; Quality of life; Research; research study; Resolution; Signal Transduction; Speech; Speech Acoustics; Speech Perception; speech processing; speech recognition; Stimulus; Techniques; Testing; transmission process; Voice; Work
Project start date: 2007-08-01
Project end date: 2012-07-31
Budget start date: 1-AUG-2011
Budget end date: 31-JUL-2012
5R01DC008594-06 (2011): $283758
HIV GAG PRECURSOR PROTEIN INTERACTIONS
W Eric, Professor
Oregon Health And Science Universitycity: Portland country: United States (us)
Grant 5R01GM060170-12 from National Institute Of General Medical Sciences
Abstract: Despite great advances in AIDS diagnosis and treatment, the continuing devastation of the AIDS epidemic demands continuing efforts to understand all aspects of HIV replication, and to develop new methods for its inhibition. In pursuit of these goals, we have sought to define the activities of the HIV-1 structural (Gag) proteins so as to design antivirals that interfere with these functions. The Gag proteins are attractive targets since they perform multiple roles during the virus life cycle. The proteins initially are synthesized as N-terminally myristylated precursor (PrGag) proteins that employ their N-terminal matrix (MA) domains to adhere to cellular membranes and promote the assembly of immature virions. During viral morphogenesis from immature to mature virus particles, the viral protease cleaves PrGag into its mature constituents MA, capsid (CA), spacer peptide 1 (SP1), nucleocapsid (NC), spacer peptide 2 (SP2), and p6. Concurrently, viral RNAs and enzymes, and cellular factors associate with NC proteins to form ribonucleoprotein complexes that are encased by highly organized conical or cylindrical cores composed of CA proteins. Using our previous studies and preliminary results as a foundation, we propose to dissect the mechanisms of membrane binding and mature core formation, and to characterize methods for their inhibition. Our results will help elucidate how the HIV assembly machinery operates; and will lead to the development of Gag-targeted antivirals, and an understanding of how they work. To achieve these ends, our specific aims are as follows 1. Elucidation of the HIV-1 CA assembly pathway and analysis of Gag-targeted inhibitor action The mechanics of HIV-1 Gag protein oligomerization and assembly will be characterized. Nucleation and growth steps and pathway alternatives will be examined with respect to their control by structural and environmental factors. The mechanisms of action of known and predicted Gag inhibitors will be determined in vitro. Our results will foster the design of practical and potent Gag-based antivirals 2. Examination of HIV-1 Gag membrane binding characteristics and binding partner interactions The membrane binding preferences of HIV-1 Gag proteins will be measured with regard to phospholipid headgroup and hydrocarbon tail contributions, and the influences of other membrane components. The manner by which Gag proteins organize on membranes will be determined, the effects of potential inhibitors will be evaluated, and interactions between different binding partners will be analyzed. These studies will establish a basis for the development of therapeutics against new HIV targets. The proposed investigations are designed to characterize how the structural proteins of HIV bind to membranes and assemble to form virus particles. The mechanisms used by inhibitors to block these activities will be determined, and will help lead to the development of new antivirals for the treatment of AIDS
Keywords: Acquired Immunodeficiency Syndrome; AIDS diagnosis; Antiviral Agents; base; Binding (Molecular Function); Capsid; Capsid Proteins; Cellular Membrane; Characteristics; Cleaved cell; Complex; design; Development; Environmental Risk Factor; Enzymes; Epidemic; Fostering; Foundations; gag Gene Products; Gagging; Goals; Growth; HIV; HIV-1; Hydrocarbons; In Vitro; inhibitor/antagonist; Investigation; Lead; Life Cycle Stages; Measures; Mechanics; Membrane; Methods; Morphogenesis; N-terminal; Nucleocapsid; Nucleocapsid Proteins; Pathway Analysis; Pathway interactions; Peptide Hydrolases; Peptides; Phospholipids; preference; Protein Precursors; Proteins; public health relevance; Ribonucleoproteins; Role; Structural Protein; Tail; therapeutic development; Viral; viral RNA; Virion; Virus; Work
Project start date: 1999-09-01
Project end date: 2012-04-30
Budget start date: 1-MAY-2011
Budget end date: 30-APR-2012
PFA/PA: PA-07-070
5R01GM060170-12 (2011): $316376