Siriwattananon Konlavat, Manopwisedjaroen Suwimon, Kanjanasirirat Phongthon, Budi Purwono Priyo, Rattanapisit Kaewta, Shanmugaraj Balamurugan, Smith Duncan R, Borwornpinyo Suparerk, Thitithanyanont Arunee, Phoolcharoen Waranyoo
Research Unit for Plant-Produced Pharmaceuticals, Chulalongkorn University, Bangkok, Thailand.
Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
Front Plant Sci. 2021 Jan 7;11:604663. doi: 10.3389/fpls.2020.604663. eCollection 2020.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease (COVID-19) which has recently emerged as a potential threat to global public health. SARS-CoV-2 is the third known human coronavirus that has huge impact on the human population after SARS-CoV and MERS-CoV. Although some vaccines and therapeutic drugs are currently in clinical trials, none of them are approved for commercial use yet. As with SARS-CoV, SARS-CoV-2 utilizes angiotensin-converting enzyme 2 (ACE2) as the cell entry receptor to enter into the host cell. In this study, we have transiently produced human ACE2 fused with the Fc region of human IgG1 in and the neutralization efficacy of the plant-produced ACE2-Fc fusion protein was assessed. The recombinant ACE2-Fc fusion protein was expressed in at 100 μg/g leaf fresh weight on day 6 post-infiltration. The recombinant fusion protein showed potent binding to receptor binding domain (RBD) of SARS-CoV-2. Importantly, the plant-produced fusion protein exhibited potent anti-SARS-CoV-2 activity . Treatment with ACE2-Fc fusion protein after viral infection dramatically inhibit SARS-CoV-2 infectivity in Vero cells with an IC value of 0.84 μg/ml. Moreover, treatment with ACE2-Fc fusion protein at the pre-entry stage suppressed SARS-CoV-2 infection with an IC of 94.66 μg/ml. These findings put a spotlight on the plant-produced ACE2-Fc fusion protein as a potential therapeutic candidate against SARS-CoV-2.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是冠状病毒病（COVID-19）的病原体，最近已成为对全球公共卫生的潜在威胁。SARS-CoV-2是已知的第三种对人类有巨大影响的人类冠状病毒，仅次于严重急性呼吸综合征冠状病毒（SARS-CoV）和中东呼吸综合征冠状病毒（MERS-CoV）。尽管目前一些疫苗和治疗药物正在进行临床试验，但尚无一种获批用于商业用途。与SARS-CoV一样，SARS-CoV-2利用血管紧张素转换酶2（ACE2）作为细胞进入受体进入宿主细胞。在本研究中，我们在植物中瞬时表达了与人IgG1的Fc区域融合的人ACE2，并评估了植物产生的ACE2-Fc融合蛋白的中和效力。重组ACE2-Fc融合蛋白在浸润后第6天在植物中以100μg/g叶片鲜重表达。重组融合蛋白显示出与SARS-CoV-2的受体结合域（RBD）有强结合。重要的是，植物产生的融合蛋白表现出强大的抗SARS-CoV-2活性。病毒感染后用ACE2-Fc融合蛋白处理可显著抑制SARS-CoV-2在Vero细胞中的感染性，IC值为0.84μg/ml。此外，在进入前阶段用ACE2-Fc融合蛋白处理可抑制SARS-CoV-2感染，IC为94.66μg/ml。这些发现使植物产生的ACE2-Fc融合蛋白成为对抗SARS-CoV-2的潜在治疗候选物备受关注。
