Conserved Sequences from Dengue Virus Genomes Form Stable G-Quadruplexes.

IF 4 2区 医学 Q2 CHEMISTRY, MEDICINAL
ACS Infectious Diseases Pub Date : 2025-01-10 Epub Date: 2024-12-12 DOI:10.1021/acsinfecdis.4c00615
Jessica L Siemer, Thao T Le, Ananya Paul, David W Boykin, Margo A Brinton, W David Wilson, Markus W Germann
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引用次数: 0

Abstract

Arthropod-borne members of the genus Orthoflavivirus cause significant human disease. Four serotypes of dengue virus are endemic globally, and approximately 50 percent of the world's population lives in a dengue-affected area. Complications from immunoenhancement occurring after a secondary infection with a different dengue serotype make vaccine development challenging. Antiviral therapies that target features conserved in all four serotypes would, therefore, be beneficial. Computational studies identified multiple potential G-quadruplex sites that are conserved in the RNA genome sequences of members of the genus Orthoflavivirus. Biophysical studies confirmed that the NS5-B quadruplex sequences obtained from viruses of each dengue serotype can form quadruplexes in vitro, and binding data showed that known quadruplex binders stabilized NS5-B quadruplexes for all four dengue serotypes.

登革病毒基因组的保守序列形成稳定的g -四联体。
节肢动物传播的原黄病毒属成员引起重大的人类疾病。登革热病毒有四种血清型在全球流行,世界上大约50%的人口生活在登革热疫区。不同登革热血清型继发感染后免疫增强的并发症使疫苗开发具有挑战性。因此,针对所有四种血清型中保留的特征的抗病毒治疗将是有益的。计算研究确定了在原黄病毒属成员的RNA基因组序列中保守的多个潜在的g -四重体位点。生物物理研究证实,从每种登革热血清型病毒中获得的NS5-B四重体序列在体外可形成四重体,结合数据显示,已知的四重体结合物稳定了所有四种登革热血清型的NS5-B四重体。
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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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