Strategies in the Design of Antiviral Drugs

Clercq, Erik De; Herdewijn, Piet

doi:10.1002/9780470571224.pse026

Cited by 54 publications

(69 citation statements)

References 131 publications

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“…Because of an increased understanding of the molecular mechanisms of viral life cycles, many viral proteins have emerged as targets for therapeutic intervention. However, antiviral drug discovery can be targeted at either viral proteins or cellular proteins as in the case of Selzentry® (maraviroc, targeting CCR5) for human immunodeficiency virus (HIV) (11). Although the former is likely to yield compounds with a narrow spectrum of antiviral activity, few effective and safe agents have emerged, and these face the inextricable challenge of high mutation rates that have confounded many conventional antiviral products.…”

mentioning

confidence: 99%

Identification of broad-spectrum antiviral compounds and assessment of the druggability of their target for efficacy against respiratory syncytial virus (RSV)

Bonavia¹,

Franti²,

Keaney³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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The search for novel therapeutic interventions for viral disease is a challenging pursuit, hallmarked by the paucity of antiviral agents currently prescribed. Targeting of viral proteins has the inextricable challenge of rise of resistance. Safe and effective vaccines are not possible for many viral pathogens. New approaches are required to address the unmet medical need in this area. We undertook a cell-based high-throughput screen to identify leads for development of drugs to treat respiratory syncytial virus (RSV), a serious pediatric pathogen. We identified compounds that are potent (nanomolar) inhibitors of RSV in vitro in HEp-2 cells and in primary human bronchial epithelial cells and were shown to act postentry. Interestingly, two scaffolds exhibited broad-spectrum activity among multiple RNA viruses. Using the chemical matter as a probe, we identified the targets and identified a common cellular pathway: the de novo pyrimidine biosynthesis pathway. Both targets were validated in vitro and showed no significant cell cytotoxicity except for activity against proliferative B- and T-type lymphoid cells. Corollary to this finding was to understand the consequences of inhibition of the target to the host. An in vivo assessment for antiviral efficacy failed to demonstrate reduced viral load, but revealed microscopic changes and a trend toward reduced pyrimidine pools and findings in histopathology. We present here a discovery program that includes screen, target identification, validation, and druggability that can be broadly applied to identify and interrogate other host factors for antiviral effect starting from chemical matter of unknown target/mechanism of action.

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confidence: 99%

Identification of broad-spectrum antiviral compounds and assessment of the druggability of their target for efficacy against respiratory syncytial virus (RSV)

Bonavia¹,

Franti²,

Keaney³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…For new drug development, the replication inhibitors are midst of the top priorities as many virus diseases are yet non-curable. Acyclo-guanosine, popularly known as acyclovir is a nucleoside analogue that drastically slows down the Herpes virus infection [90,91]. Carbohydrate-binding agents might also act as inhibitors binds by masking the glycans present on the viral envelope.…”

Section: Resultsmentioning

confidence: 99%

Antiviral Phytochemicals: An Overview

Kapoor¹,

Sharma²,

Kanwar³

2017

Biochem Physiol

100

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The pandemic of viral diseases during recent years has forced the scientific community to investigate less toxic antiviral phytomolecules instead of using nucleic acid analogues, protease inhibitors or other toxic synthetic molecules as antiviral therapeutics. Plants and many of their secondary metabolites because of the healing properties have been in traditional use throughout the world since ancient times. They provide us diverse bioactive phytochemicals which play synergetic role in maintaining human health. The development of clinical products from phyto-pharmaceuticals is a trending approach to look for ecofriendly therapeutic molecules. More than 50% of drugs used in Western nations are derived from plants or their constituents. Many plants have significant antiviral properties too. Very little information is available about plants of antiviral significance. This article briefly reviews various phytochemicals/bioactive molecules which have been isolated from plants and possess antiviral constituents, their mode of action and potential applications in treating/preventing viral diseases.

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“…[134,135] Moreover, the offered antiviral therapies are not always welltolerated or to a certain extent effective and satisfactory. [136] Henceforth, in recent days, the increasing requirement for antiviral substances is more emphasized. It has been wellknown that curcumin as a plant derivative has a widespread range of antiviral activity against different viruses.…”

Section: Antiviral Effectmentioning

confidence: 99%

Untitled

Ashraf¹

2017

IJGP

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Curcuma longa Linn. is well-known and valued medicinal plant. It has a long history of traditional uses ranging from folk medicine to several culinary preparations. The phytochemical, pharmacological, and molecular studies of C. longa are reviewed. The rhizome is rich in essential oils, and various numbers of chemical constituents with biomedical significance have been isolated from it. The management of indigenous knowledge by appropriate documentation is recommended. This review was compiled to provide recent consolidated information covering different aspects of the plant, phytochemical, pharmacological, and molecular study to provide a basis on which to plan future studies and to promote sustainable use of C. longa.

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Strategies in the Design of Antiviral Drugs

Cited by 54 publications

References 131 publications

Identification of broad-spectrum antiviral compounds and assessment of the druggability of their target for efficacy against respiratory syncytial virus (RSV)

Identification of broad-spectrum antiviral compounds and assessment of the druggability of their target for efficacy against respiratory syncytial virus (RSV)

Antiviral Phytochemicals: An Overview

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