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评估抗病毒药物对新出现的 SARS-CoV-2 奥密克戎亚型的作用。

Evaluation of antiviral drugs against newly emerged SARS-CoV-2 Omicron subvariants.

机构信息

Division of Emerging Viral Diseases and Vector Research, Center for Emerging Virus Research, National Institute of Infectious Diseases, Korea National Institute of Health, Korea Centers for Disease Control and Prevention, Cheongju, Republic of Korea.

Division of Emerging Viral Diseases and Vector Research, Center for Emerging Virus Research, National Institute of Infectious Diseases, Korea National Institute of Health, Korea Centers for Disease Control and Prevention, Cheongju, Republic of Korea.

出版信息

Antiviral Res. 2023 Jun;214:105609. doi: 10.1016/j.antiviral.2023.105609. Epub 2023 Apr 20.


DOI:10.1016/j.antiviral.2023.105609
PMID:37086978
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10118056/
Abstract

Ongoing emergence of SARS-CoV-2 Omicron subvariants and their rapid worldwide spread pose a threat to public health. From November 2022 to February 2023, newly emerged Omicron subvariants, including BQ.1.1, BF.7, BA.5.2, XBB.1, XBB.1.5, and BN.1.9, became prevalent global strains (>5% global prevalence). These Omicron subvariants are resistant to several therapeutic antibodies. Thus, the antiviral activity of current drugs such as remdesivir, molnupiravir, and nirmatrelvir, which target highly conserved regions of SARS-CoV-2, against newly emerged Omicron subvariants need to be evaluated. We assessed the antiviral efficacy of the drugs using the half-maximal inhibitory concentration (IC) against human isolates of 23 Omicron subvariants and four former SARS-CoV-2 variants of concern (VOCs) and compared it with the antiviral efficacy of these drugs against the SARS-CoV-2 reference strain (hCoV/Korea/KCDC03/2020). Maximal IC-fold changes of remdesivir, molnupiravir, and nirmatrelvir were 1.9 (BA.2.75.2), 1.2 (B.1.627.2), and 1.4 (BA.2.3), respectively, compared to median IC values of the reference strain. Moreover, median IC-fold changes of remdesivir, molnupiravir, and nirmatrelvir against the Omicron variants were 0.96, 0.4, and 0.62, respectively, similar to the 1.02, 0.88, and 0.67, respectively, median IC-fold changes for previous VOCs. Although K90R and P132H in Nsp 5, and P323L, A529V, G671S, V405F, and ins823D in Nsp 12 mutations were identified, these amino acid substitutions did not affect drug antiviral activity. These results indicate that current antivirals retain antiviral efficacy against newly emerged Omicron subvariants. It is important to continue active surveillance and testing of new variants for drug resistance to enable early identification of drug-resistant strains.

摘要

持续出现的 SARS-CoV-2 奥密克戎亚变种及其在全球范围内的迅速传播对公共卫生构成威胁。从 2022 年 11 月到 2023 年 2 月,新出现的奥密克戎亚变种,包括 BQ.1.1、BF.7、BA.5.2、XBB.1、XBB.1.5 和 BN.1.9,成为流行的全球毒株(全球流行率超过 5%)。这些奥密克戎亚变种对几种治疗性抗体具有耐药性。因此,需要评估当前药物(如瑞德西韦、莫那比拉韦和奈玛特韦)的抗病毒活性,这些药物针对的是 SARS-CoV-2 的高度保守区域,而针对新出现的奥密克戎亚变种的抗病毒活性需要评估。我们使用 23 种奥密克戎亚变种和 4 种以前的 SARS-CoV-2 关切变种(VOC)的人类分离株的半数最大抑制浓度(IC)评估了这些药物的抗病毒功效,并将其与这些药物对 SARS-CoV-2 参考株(hCoV/Korea/KCDC03/2020)的抗病毒功效进行了比较。与参考株的中位数 IC 值相比,瑞德西韦、莫那比拉韦和奈玛特韦的最大 IC 倍增加分别为 1.9(BA.2.75.2)、1.2(B.1.627.2)和 1.4(BA.2.3)。此外,瑞德西韦、莫那比拉韦和奈玛特韦对奥密克戎变种的中位数 IC 倍增加分别为 0.96、0.4 和 0.62,与之前的 VOC 相比,中位数 IC 倍增加分别为 1.02、0.88 和 0.67,相似。尽管在 Nsp 5 中发现了 K90R 和 P132H,以及在 Nsp 12 中发现了 P323L、A529V、G671S、V405F 和 ins823D 突变,但这些氨基酸取代并未影响药物的抗病毒活性。这些结果表明,目前的抗病毒药物对新出现的奥密克戎亚变种仍具有抗病毒功效。重要的是要继续对新变种进行积极监测和检测,以了解耐药性,从而能够早期发现耐药菌株。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4c4/10118056/5c60b9861d33/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4c4/10118056/5c60b9861d33/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4c4/10118056/5c60b9861d33/gr1_lrg.jpg

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本文引用的文献

[1]
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ACS Cent Sci. 2023-7-24

[2]
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Antimicrob Agents Chemother. 2022-6-21

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Bioorg Med Chem Lett. 2022-4-15

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Remdesivir, Molnupiravir and Nirmatrelvir remain active against SARS-CoV-2 Omicron and other variants of concern.

Antiviral Res. 2022-2

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