Inhibitors of the Structural and Nonstructural Proteins of Alphaviruses.

IF 4 2区 医学 Q2 CHEMISTRY, MEDICINAL
ACS Infectious Diseases Pub Date : 2024-08-09 Epub Date: 2024-07-11 DOI:10.1021/acsinfecdis.4c00254
Damilohun Samuel Metibemu, Olawale Samuel Adeyinka, John Falode, Olamide Crown, Ifedayo Victor Ogungbe
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引用次数: 0

Abstract

The Alphavirus genus includes viruses that cause encephalitis due to neuroinvasion and viruses that cause arthritis due to acute and chronic inflammation. There is no approved therapeutic for alphavirus infections, but significant efforts are ongoing, more so in recent years, to develop vaccines and therapeutics for alphavirus infections. This review article highlights some of the major advances made so far to identify small molecules that can selectively target the structural and the nonstructural proteins in alphaviruses with the expectation that persistent investigation of an increasingly expanding chemical space through a variety of structure-based design and high-throughput screening strategies will yield candidate drugs for clinical studies. While most of the works discussed are still in the early discovery to lead optimization stages, promising avenues remain for drug development against this family of viruses.

Abstract Image

阿尔法病毒结构蛋白和非结构蛋白的抑制剂。
阿尔法病毒属包括因神经入侵而引起脑炎的病毒,以及因急性和慢性炎症而引起关节炎的病毒。目前还没有针对阿尔法病毒感染的获准疗法,但人们一直在努力开发针对阿尔法病毒感染的疫苗和疗法,近年来更是如此。这篇综述文章重点介绍了迄今为止在确定可选择性靶向阿尔法病毒结构蛋白和非结构蛋白的小分子方面取得的一些重大进展,希望通过各种基于结构的设计和高通量筛选策略,对日益扩大的化学空间进行持续研究,从而产生可用于临床研究的候选药物。虽然所讨论的大多数研究工作仍处于早期发现到先导优化阶段,但针对这一病毒家族的药物开发仍大有可为。
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来源期刊
ACS Infectious Diseases
ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES
CiteScore
9.70
自引率
3.80%
发文量
213
期刊介绍: ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to: * Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials. * Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets. * Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance. * Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents. * Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota. * Small molecule vaccine adjuvants for infectious disease. * Viral and bacterial biochemistry and molecular biology.
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