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植物源人重组 ACE2 对金黄地鼠 COVID-19 模型的疗效。

Efficacy of Plant-Made Human Recombinant ACE2 against COVID-19 in a Golden Syrian Hamster Model.

机构信息

Premedical Science, Chosun University College of Medicine, Gwangju 61452, Republic of Korea.

Department of Internal Medicine, Chosun University College of Medicine, Gwangju 61452, Republic of Korea.

出版信息

Viruses. 2023 Apr 14;15(4):964. doi: 10.3390/v15040964.

DOI:10.3390/v15040964
PMID:37112944
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10146983/
Abstract

Coronavirus disease 2019 (COVID-19) is a novel infectious respiratory disease caused by SARS-CoV-2. We evaluated the efficacy of a plant-based human recombinant angiotensin-converting enzyme 2 (hrACE2) and hrACE2-foldon (hrACE2-Fd) protein against COVID-19. In addition, we analyzed the antiviral activity of hrACE2 and hrACE2-Fd against SARS-CoV-2 using real-time reverse-transcription PCR and plaque assays. The therapeutic efficacy was detected using the Golden Syrian hamster model infected with SARS-CoV-2. Both hrACE2 and hrACE2-Fd inhibited SARS-CoV-2 by 50% at concentrations below the maximum plasma concentration, with EC of 5.8 μg/mL and 6.2 μg/mL, respectively. The hrACE2 and hrACE2-Fd injection groups showed a tendency for decreased viral titers in nasal turbinate tissues on day 3 after virus inoculation; however, this decrease was not detectable in lung tissues. Histopathological examination on day 9 after virus inoculation showed continued inflammation in the SARS-CoV-2 infection group, whereas decreased inflammation was observed in both the hrACE2 and hrACE2-Fd injection groups. No significant changes were observed at other time points. In conclusion, the potential therapeutic efficacy of plant-based proteins, hrACE2 and hrACE2-Fd, against COVID-19 was confirmed in a SARS-CoV-2-inoculated Golden Syrian hamster model. Further preclinical studies on primates and humans are necessary to obtain additional evidence and determine the effectiveness of these therapies.

摘要

新型冠状病毒病（COVID-19）是一种由 SARS-CoV-2 引起的新型传染性呼吸道疾病。我们评估了植物源性人重组血管紧张素转换酶 2（hrACE2）和 hrACE2 折叠体（hrACE2-Fd）蛋白对 COVID-19 的疗效。此外，我们使用实时逆转录 PCR 和蚀斑分析，分析了 hrACE2 和 hrACE2-Fd 对 SARS-CoV-2 的抗病毒活性。使用感染 SARS-CoV-2 的金黄地鼠模型检测治疗效果。在低于最大血浆浓度的浓度下，hrACE2 和 hrACE2-Fd 均能抑制 SARS-CoV-2 的活性，EC50 值分别为 5.8μg/mL 和 6.2μg/mL。在病毒接种后第 3 天，hrACE2 和 hrACE2-Fd 注射组的鼻甲骨组织中的病毒滴度有降低的趋势，但在肺组织中则无法检测到。在病毒接种后第 9 天的组织病理学检查显示，SARS-CoV-2 感染组仍存在持续的炎症，而 hrACE2 和 hrACE2-Fd 注射组的炎症则有所减轻。在其他时间点则未观察到明显变化。总之，在 SARS-CoV-2 感染的金黄地鼠模型中，证实了植物源性蛋白 hrACE2 和 hrACE2-Fd 对 COVID-19 的潜在治疗效果。需要在灵长类动物和人类中进行进一步的临床前研究，以获得更多的证据并确定这些疗法的有效性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/714a/10146983/3630deb4cb28/viruses-15-00964-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/714a/10146983/19249470b64e/viruses-15-00964-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/714a/10146983/b1819324f756/viruses-15-00964-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/714a/10146983/ca7f1baf2b1d/viruses-15-00964-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/714a/10146983/c151c405aa38/viruses-15-00964-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/714a/10146983/3630deb4cb28/viruses-15-00964-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/714a/10146983/19249470b64e/viruses-15-00964-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/714a/10146983/b1819324f756/viruses-15-00964-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/714a/10146983/ca7f1baf2b1d/viruses-15-00964-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/714a/10146983/c151c405aa38/viruses-15-00964-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/714a/10146983/3630deb4cb28/viruses-15-00964-g005.jpg

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