The challenge of emerging and re-emerging infectious diseases

Morens, David M.; Folkers, Gregory K.; Fauci, Anthony S.

doi:10.1038/nature02759

Cited by 1,750 publications

(1,289 citation statements)

References 74 publications

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“…1b). Several million more deaths occur each year from complications of chronic infections [47]. Despite advances in treatment options, significant work remains towards the eradication of infectious diseases.…”

Section: Challenges Of Hepatitis C Drug Developmentmentioning

confidence: 99%

“…Throughout history, the impact of infectious diseases on human society has been staggering, reaching across numerous sectors including economy, sociology, healthcare, politics, and education [47]. At present, over 25% of the approximately 57 million annual deaths in the world are the direct result of infectious diseases [47] (Fig.…”

Section: Challenges Of Hepatitis C Drug Developmentmentioning

confidence: 99%

“…1a). Within this number, several classes of disease individually cause the deaths of hundreds of thousands or even millions of people per year [47] (Fig. 1b).…”

Section: Challenges Of Hepatitis C Drug Developmentmentioning

confidence: 99%

“…At present, over 25% of the approximately 57 million annual deaths in the world are the direct result of infectious diseases [47] (Fig. 1a).…”

Section: Challenges Of Hepatitis C Drug Developmentmentioning

confidence: 99%

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Model Membrane Platforms for Biomedicine: Case Study on Antiviral Drug Development

Jackman

Cho

2012

Biointerphases

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As one of the most important interfaces in cellular systems, biological membranes have essential functions in many activities such as cellular protection and signaling. Beyond their direct functions, they also serve as scaffolds to support the association of proteins involved in structural support, adhesion, and transport. Unfortunately, biological processes sometimes malfunction and require therapeutic intervention. For those processes which occur within or upon membranes, it is oftentimes difficult to study the mechanism in a biologically relevant, membranous environment. Therefore, the identification of direct therapeutic targets is challenging. In order to overcome this barrier, engineering strategies offer a new approach to interrogate biological activities at membrane interfaces by analyzing them through the principles of the interfacial sciences. Since membranes are complex biological interfaces, the development of simplified model systems which mimic important properties of membranes can enable fundamental characterization of interaction parameters for such processes. We have selected the hepatitis C virus (HCV) as a model viral pathogen to demonstrate how model membrane platforms can aid antiviral drug discovery and development. Responsible for generating the genomic diversity that makes treating HCV infection so difficult, viral replication represents an ideal step in the virus life cycle for therapeutic intervention. To target HCV genome replication, the interaction of viral proteins with model membrane platforms has served as a useful strategy for target identification and characterization. In this review article, we demonstrate how engineering approaches have led to the discovery of a new functional activity encoded within the HCV nonstructural 5A protein. Specifically, its N-terminal amphipathic, α-helix (AH) can rupture lipid vesicles in a size-dependent manner. While this activity has a number of exciting biotechnology and biomedical applications, arguably the most promising one is in antiviral medicine. Based on the similarities between lipid vesicles and the lipid envelopes of virus particles, experimental findings from model membrane platforms led to the prediction that a range of medically important viruses might be susceptible to rupturing treatment with synthetic AH peptide. This hypothesis was tested and validated by molecular virology studies. Broad-spectrum antiviral activity of the AH peptide has been identified against HCV, HIV, herpes simplex virus, and dengue virus, and many more deadly pathogens. As a result, the AH peptide is the first in class of broad-spectrum, lipid envelope-rupturing antiviral agents, and has entered the drug pipeline. In summary, engineering strategies break down complex biological systems into simplified biomimetic models that recapitulate the most important parameters. This approach is particularly advantageous for membrane-associated biological processes because model membrane platforms provide more direct characterization of target interactions than is possible with other methods. Consequently, model membrane platforms hold great promise for solving important biomedical problems and speeding up the translation of biological knowledge into clinical applications.

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Section: Challenges Of Hepatitis C Drug Developmentmentioning

confidence: 99%

Section: Challenges Of Hepatitis C Drug Developmentmentioning

confidence: 99%

“…1a). Within this number, several classes of disease individually cause the deaths of hundreds of thousands or even millions of people per year [47] (Fig. 1b).…”

Section: Challenges Of Hepatitis C Drug Developmentmentioning

confidence: 99%

“…At present, over 25% of the approximately 57 million annual deaths in the world are the direct result of infectious diseases [47] (Fig. 1a).…”

Section: Challenges Of Hepatitis C Drug Developmentmentioning

confidence: 99%

See 2 more Smart Citations

Model Membrane Platforms for Biomedicine: Case Study on Antiviral Drug Development

Jackman

Cho

2012

Biointerphases

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show abstract

“…The pathogenicity of an organism is determined by its virulence factors that is typically proteins coded for by genes in chromosomal DNA or plasmids [1]. Identification of virulent proteins that cause drug resistant varieties of various bacterial pathogen evoke the design of peptide based vaccine and drug.…”

Section: Introductionmentioning

confidence: 99%

Prediction of Bacterial Virulent Proteins with Composition Moment Vector Feature Encoding Method

Gök

Herand

2016

MATEC Web of Conferences

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Abstract. Prediction of bacterial virulent proteins is critical for vaccine development and understanding of virulence mechanisms in pathogens. For this purpose, a number of feature encoding methods based on sequences and evolutionary information of a given protein have been proposed and applied with some classifier algorithms so far. In this paper, we performed composition moment vector (CMV), which includes information about both composition and position of amino acid in the protein sequence to predict bacterial virulent proteins. The tests were validated in three different independent datasets. Experimental results show that CMV feature encoding method leads to better classification performance in terms of accuracy, sensitivity, f-measure and the Matthews correlation coefficient (MCC) scores on diverse classifiers.

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Universal Patient Disinfection as a Tool for Infection Control

Peterson¹,

Singh²

2006

Arch Intern Med

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The challenge of emerging and re-emerging infectious diseases

Cited by 1,750 publications

References 74 publications

Model Membrane Platforms for Biomedicine: Case Study on Antiviral Drug Development

Model Membrane Platforms for Biomedicine: Case Study on Antiviral Drug Development

Prediction of Bacterial Virulent Proteins with Composition Moment Vector Feature Encoding Method

Universal Patient Disinfection as a Tool for Infection Control

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