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