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一种针对 SARS-CoV-2 变体设计和验证小干扰 RNA 的计算方法。

A Computational Approach for Designing and Validating Small Interfering RNA against SARS-CoV-2 Variants.

机构信息

Division of Virology, ICMR-National AIDS Research Institute, Pune, MH, India.

Division of Molecular Biology, ICMR-National AIDS Research Institute, Pune, MH, India.

出版信息

Curr Comput Aided Drug Des. 2024;20(6):876-887. doi: 10.2174/1573409920666230825111406.

Abstract

AIMS

The aim of this study is to develop a novel antiviral strategy capable of efficiently targeting a broad set of SARS-CoV-2 variants.

BACKGROUND

Since the first emergence of SARS-CoV-2, it has rapidly transformed into a global pandemic, posing an unprecedented threat to public health. SARS-CoV-2 is prone to mutation and continues to evolve, leading to the emergence of new variants capable of escaping immune protection achieved due to previous SARS-CoV-2 infections or by vaccination.

OBJECTIVE

RNA interference (RNAi) is a remarkable biological mechanism that can induce gene silencing by targeting complementary mRNA and inhibiting its translation.

METHODS

In this study, using the computational approach, we predicted the most efficient siRNA capable of inhibiting SARS-CoV-2 variants of concern (VoCs).

RESULTS

The presented siRNA was characterized and evaluated for its thermodynamic properties, offsite-target hits, and in silico validation by molecular docking and molecular dynamics simulations (MD) with Human AGO2 protein.

CONCLUSION

The study contributes to the possibility of designing and developing an effective response strategy against existing variants of concerns and preventing further.

摘要

目的

本研究旨在开发一种新的抗病毒策略,能够有效地针对广泛的 SARS-CoV-2 变体。

背景

自 SARS-CoV-2 首次出现以来,它迅速演变成一种全球大流行,对公共卫生构成了前所未有的威胁。SARS-CoV-2 容易发生突变并不断进化,导致能够逃避因先前 SARS-CoV-2 感染或接种疫苗而产生的免疫保护的新变体的出现。

目的

RNA 干扰 (RNAi) 是一种通过靶向互补 mRNA 并抑制其翻译来诱导基因沉默的非凡生物学机制。

方法

在这项研究中,我们使用计算方法预测了最有效的 siRNA,能够抑制关注的 SARS-CoV-2 变体 (VoCs)。

结果

对所提出的 siRNA 的热力学性质、脱靶靶点和分子对接以及与人类 AGO2 蛋白的分子动力学模拟 (MD) 进行了表征和评估。

结论

该研究为设计和开发针对现有关注变体的有效应对策略以及防止进一步的策略提供了可能性。

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