Novel Dual Small-Molecule HIV inhibitors: Scaffolds and Discovery Strategies

Viruses represent the most common cause of infectious diseases worldwide and those with rapid propagation and high infection rates cause human and animal pandemics. These fast-spreading diseases are generally treated with antiviral drugs but, often, drug resistance occurs because of the ability of the pathogens to mutate rapidly and become less susceptible to the treatments. Even though new antivirals have been approved, e.g., in HIV (human immunodeficiency virus) and HCV (hepatitis C virus) therapeutic areas, the need to dispose of new pharmaceutical tools for the management of infections that still have no treatment is of growing interest. In these areas, carbazole represents an important privileged scaffold in drug discovery. Many compounds with a carbazolic core have been developed and some of them have shown antiviral activity. This review provides an overview on some already known carbazole derivatives, pointing the attention on the running progresses in identifying new molecules with carbazolic structure, that have shown interesting and encouraging in vitro and in vivo properties. These drugs may be exploited as valid alternatives in antiviral therapy.

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“…Thus, the study of novel compounds with HIV activity is very attractive and it challenges research fields [40,41,42].…”

Section: Human Immunodeficiency Virus (Hiv)mentioning

confidence: 99%

Carbazole Derivatives as Antiviral Agents: An Overview

et al. 2019

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“…Matsumoto et al have reported the strategy of linking PR and RT inhibitor by spontaneously cleavable linker (Matsumoto et al, 2000). Furthermore, scaffold merging strategy is successfully applied in designing multi-target anti-HIV inhibitors in recent years (Song et al, 2015;Sun et al, 2016). However, both the dependency of known inhibitors and specific requirement of molecular structure limit the practical applications of structure merging strategy.…”

Section: Application Of Ligbuiler V3 In Multi-target Ligand Designmentioning

confidence: 99%

LigBuilder V3: A Multi-Target de novo Drug Design Approach

2020

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With the rapid development of systems-based pharmacology and poly-pharmacology, method development for rational design of multi-target drugs has becoming urgent. In this paper, we present the first de novo multi-target drug design program LigBuilder V3, which can be used to design ligands to target multiple receptors, multiple binding sites of one receptor, or various conformations of one receptor. LigBuilder V3 is generally applicable in de novo multi-target drug design and optimization, especially for the design of concise ligands for protein targets with large difference in binding sites. To demonstrate the utility of LigBuilder V3, we have used it to design dual-functional inhibitors targeting HIV protease and HIV reverse transcriptase with three different strategy, including multi-target de novo design, multi-target growing, and multi-target linking. The designed compounds were computational validated by MM/GBSA binding free energy estimation as highly potential multi-target inhibitors for both HIV protease and HIV reverse transcriptase. The LigBuilder V3 program can be downloaded at "http:// www.pkumdl.cn/ligbuilder3/".

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“…have reported the strategy of linking PR and RT inhibitor by spontaneously cleavable linker (Matsumoto et al, 2000). Furthermore, scaffold merging strategy is successfully applied in designing multi-target anti-HIV inhibitors in recent years (Song et al, 2015;Sun et al, 2016). However, both the dependency of known inhibitors and specific requirement of molecular structure limit the practical applications of structure merging strategy.…”

Section: Application Of Ligbuiler V3 In Multi-target Ligand Designmentioning

confidence: 99%

In Silico Methods for Drug Design and Discovery

Brogi¹,

Ramalho²,

Kuča³

et al. 2020

Frontiers Research Topics

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Frontiers in Chemistry 1October 2020 | In silico Methods for Drug Design and Discovery About FrontiersFrontiers is more than just an open-access publisher of scholarly articles: it is a pioneering approach to the world of academia, radically improving the way scholarly research is managed. The grand vision of Frontiers is a world where all people have an equal opportunity to seek, share and generate knowledge. Frontiers provides immediate and permanent online open access to all its publications, but this alone is not enough to realize our grand goals. Frontiers Journal SeriesThe Frontiers Journal Series is a multi-tier and interdisciplinary set of open-access, online journals, promising a paradigm shift from the current review, selection and dissemination processes in academic publishing. All Frontiers journals are driven by researchers for researchers; therefore, they constitute a service to the scholarly community. At the same time, the Frontiers Journal Series operates on a revolutionary invention, the tiered publishing system, initially addressing specific communities of scholars, and gradually climbing up to broader public understanding, thus serving the interests of the lay society, too. Dedication to QualityEach Frontiers article is a landmark of the highest quality, thanks to genuinely collaborative interactions between authors and review editors, who include some of the world's best academicians. Research must be certified by peers before entering a stream of knowledge that may eventually reach the public -and shape society; therefore, Frontiers only applies the most rigorous and unbiased reviews.Frontiers revolutionizes research publishing by freely delivering the most outstanding research, evaluated with no bias from both the academic and social point of view.By applying the most advanced information technologies, Frontiers is catapulting scholarly publishing into a new generation.

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Novel Dual Small-Molecule HIV inhibitors: Scaffolds and Discovery Strategies

Cited by 7 publications

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Carbazole Derivatives as Antiviral Agents: An Overview

Carbazole Derivatives as Antiviral Agents: An Overview

LigBuilder V3: A Multi-Target de novo Drug Design Approach

In Silico Methods for Drug Design and Discovery

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