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聚氨酸逆向高斯廷针头作为SARS-CoV-2感染的治疗工具

Carlos J Ciudad¹, Simonas Valiuska¹, José Manuel Rojas²

¹Department of Biochemistry & Physiology, School Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain; Institut de Nanociencia i Nanotecnologia (IN2UB), Universitat de Barcelona, Barcelona, Spain.

The Journal of biological chemistry

|October 12, 2024

概括

聚氨酸逆针头 (PPRHs) 显示出作为抗病毒疗法对抗SARS-CoV-2的重大潜力. 这些分子有效地抑制了细胞培养中的病毒复制,并保护小鼠免受感染,突出显示了它们的治疗前景.

科学领域:

分子生物学分子生物学
病毒学病毒学
抗菌研究抗菌研究

背景情况:

严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2) 仍然是一个全球健康问题,尽管世卫组织宣布COVID-19大流行不再是全球紧急情况.
基于寡核酸的疗法,包括反感性寡核酸 (ASO),小干扰RNA (siRNA) 和CRISPR系统,正在成为有前途的抗病毒策略.
聚氨酸反向钉头发针 (PPRHs) 之前已经被验证用于COVID-19诊断.

研究的目的:

调查特定的聚氨酸逆针头 (PPRH),即CC1-PPRH和CC3-PPRH,抑制SARS-CoV-2复制的潜力.
评估PPRHs与SARS-CoV-2基因组内的目标序列的结合亲和力.
评估PPRHs作为抗病毒剂对SARS-CoV-2的体外和体内疗效.

主要方法:

在SARS-CoV-2复制酶和尖端区域中合成和表征CC1-PPRH和CC3-PPRH向聚皮里米丁序列.
使用生物物理方法 (报告为nM顺序) 确定PPRHs与病毒RNA序列的结合亲和力.
在体外抗病毒试验中,涉及VERO-E6细胞与PPRHs的传染,随后感染SARS-CoV-2.
在体内研究中,使用K18-hACE2转基因小鼠在SARS-CoV-2挑战之前注射CC1-PPRH鼻入.

主要成果:

无论是CC1-PPRH还是CC3-PPRH,都表现出高结合亲和力 (nM范围) 与 SARS-CoV-2 基因组中的各自目标序列.
在体外,PPRHs在感染前24小时内在VERO-E6细胞中减少了超过92%的SARS-CoV-2病毒复制.
在K18-hACE2小鼠中注射CC1-PPRH导致了对SARS-CoV-2感染的完全保护.

结论:

在体外和体外模型中,聚氨酸逆头针 (PPRHs) 对SARS-CoV-2表现出强大的抗病毒活性.
高结合亲和力和显著减少病毒复制的位置PPRHs作为新型抗病毒疗法的有希望的候选人.
PPRHs不仅代表SARS-CoV-2,也代表其他病毒感染的潜在治疗策略.

关键词:

在PPRH的基础上,PPRH 这就是SARS-CoV-2病毒.这是一种寡核化物.流行病是一种流行病.治疗疗法治疗疗法治疗疗法

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