New horizons for antiviral drug discovery from virus–host protein interaction networks

Chassey, Benoı̂t de; Meyniel-Schicklin, Laurène; Aublin-Gex, Anne; André, Patrice; Lotteau, Vincent

doi:10.1016/j.coviro.2012.09.001

Cited by 56 publications

(52 citation statements)

References 55 publications

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“…13). Our genome-wide perspective on HIV pairwise protein associations reveals intrinsic cross talk between HIV proteins, contributing to the investigation of novel drug resistance and the development of novel antiviral agents (581)(582)(583)(584). Bear in mind that the HIV genome encodes only 16 proteins; a high level of HIV pairwise protein associations is therefore expected.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

HIV Genome-Wide Protein Associations: a Review of 30 Years of Research

Clercq

2016

Microbiol Mol Biol Rev

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SUMMARYThe HIV genome encodes a small number of viral proteins (i.e., 16), invariably establishing cooperative associations among HIV proteins and between HIV and host proteins, to invade host cells and hijack their internal machineries. As a known example, the HIV envelope glycoprotein GP120 is closely associated with GP41 for viral entry. From a genome-wide perspective, a hypothesis can be worked out to determine whether 16 HIV proteins could develop 120 possible pairwise associations either by physical interactions or by functional associations mediated via HIV or host molecules. Here, we present the first systematic review of experimental evidence on HIV genome-wide protein associations using a large body of publications accumulated over the past 3 decades. Of 120 possible pairwise associations between 16 HIV proteins, at least 34 physical interactions and 17 functional associations have been identified. To achieve efficient viral replication and infection, HIV protein associations play essential roles (e.g., cleavage, inhibition, and activation) during the HIV life cycle. In either a dispensable or an indispensable manner, each HIV protein collaborates with another viral protein to accomplish specific activities that precisely take place at the proper stages of the HIV life cycle. In addition, HIV genome-wide protein associations have an impact on anti-HIV inhibitors due to the extensive cross talk between drug-inhibited proteins and other HIV proteins. Overall, this study presents for the first time a comprehensive overview of HIV genome-wide protein associations, highlighting meticulous collaborations between all viral proteins during the HIV life cycle.

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Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

HIV Genome-Wide Protein Associations: a Review of 30 Years of Research

Clercq

2016

Microbiol Mol Biol Rev

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“…In addition, with the advent of better screening technologies, we now know that the number of host factors associated with viral replication is strikingly large [64][65][66][67] . This provides a vast space to explore further antiviral targets 68 . Nonetheless, the development of such host-acting and broad-spectrum antivirals has its own challenges to meet.…”

Section: One For Many: the Broad-spectrum Alternativementioning

confidence: 99%

Antiviral drug discovery: broad-spectrum drugs from nature

et al. 2015

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, but cannot be converted to PDF. You must view these files (e.g. movies) online.Scheme 1_(structures 1-5)_named.cdx Scheme 2_(structures 6-8)_named.cdx Scheme 3_(structure 9)_named.cdx Scheme 4_(structure 10)_named.cdx Scheme 5_ (structures 11-12) The development of drugs with broad-spectrum antiviral activities is a long pursued goal in drug discovery. It has been shown that blocking co-opted host-factors abrogates the replication of many viruses, yet the development of such host-targeting drugs has been met with skepticism mainly due to toxicity issues and poor translation to in vivo models. With the advent of new and more powerful screening assays and prediction tools, the idea of a drug that can efficiently treat a wide range of viral infections by blocking specific host functions has rebloomed. Here we critically review the state-of-the-art in broad-spectrum antiviral drug discovery. We discuss putative targets and treatment strategies, taking particular focus on natural products as promising starting points for antiviral lead development.

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“…27 Systematic Y2H virus-host interaction screens, which are subsequently validated by a variety of methods, have been used to chart several virus-host PPIs, such as in HCV, Epstein-Barr virus (EBV), KSHV and varicella-zoster virus (VZV), dengue virus (DENV), and HIV-1. 20,[28][29][30][31][32] Chikungunya virus (CHIKV; family Togaviridae)-host-protein interactions have been investigated through HT-Y2H assays that are validated by protein interaction mapping. 33 Out of …”

Section: Early Studies On Host-virus Interactomicsmentioning

confidence: 99%

“…Few promising host-protein antagonistic drugs are ready to be launched commercially, such as Maraviroc (a CCR5 co-receptor antagonist) for the HIV treatment, DAS181 (a recombinant sialidase fusion protein) for influenza virus infection, and TSG101 (human monoclonal antibody against a surface receptor expressed in infected cell) for a variety of viruses. 32 Through a process of drug repurposing, the available libraries of small drug 32 In vitro cytopathic effects-based high-throughput screening assays to identify novel antiviral drugs against bluetongue virus, 44 influenza virus, [45][46][47] SARS-CoV, 48 yellow fever virus, 49 and Crimean-Congo hemorrhagic fever virus 50 have identified unique antivirals. In a novel modification of studying virushost interactions, a systematic large number of pair-wise drug interactions were explored.…”

Section: Antiviral Drug Screeningmentioning

confidence: 99%

Recent advances in host–virus interactomics during entry and infection

Bhattacharjee¹

2015

VAAT

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Viral infections and pandemics result in millions of deaths worldwide each year. Viruses exploit host cellular processes, not only to gain entry and to deliver their genetic cargo, but also to counteract and use host immune defenses. To this end, a variety of ingenious strategies have evolved in viruses that involve fusion between virus and host membranes, channel formation through the host plasma membranes, disruption of the membrane vesicles, or a combination of these events. The entry and infection pathways of virus are thus largely defined by the interactions between virus particles and their cell surface and cytoplasmic receptors. A thorough analysis of virus-host interactomes may reveal novel mechanisms in virus entry, virus infection, and pathogenic strategies to modulate host metabolic pathways. The study of viral entry, infection, and pathogenesis has evolved over a long period. A host of next-generation technological advancements in this field has been discussed in this review.

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New horizons for antiviral drug discovery from virus–host protein interaction networks

Cited by 56 publications

References 55 publications

HIV Genome-Wide Protein Associations: a Review of 30 Years of Research

HIV Genome-Wide Protein Associations: a Review of 30 Years of Research

Antiviral drug discovery: broad-spectrum drugs from nature

Recent advances in host–virus interactomics during entry and infection

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New horizons for antiviral drug discovery from virus–host protein interaction networks

Cited by 56 publications

References 55 publications

HIV Genome-Wide Protein Associations: a Review of 30 Years of Research

HIV Genome-Wide Protein Associations: a Review of 30 Years of Research

Antiviral drug discovery: broad-spectrum drugs from nature

Recent advances in host&ndash;virus interactomics during entry and infection

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Recent advances in host–virus interactomics during entry and infection