Scott Tristan A, Supramaniam Aroon, Idris Adi, Cardoso Angelo A, Shrivastava Surya, Kelly Gabrielle, Grepo Nicole A, Soemardy Citradewi, Ray Roslyn M, McMillan Nigel A J, Morris Kevin V
Center for Gene Therapy, City of Hope, Beckman Research Institute and Hematological Malignancy and Stem Cell Transplantation Institute at the City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USA.
Menzies Health Institute Queensland, School of Pharmacy and Medical Science, Griffith University, Gold Coast Campus, Brisbane 4222, Australia.
Mol Ther Methods Clin Dev. 2022 Mar 10;24:355-366. doi: 10.1016/j.omtm.2022.01.015. Epub 2022 Feb 2.
SARS-CoV-2 (CoV-2) viral infection results in COVID-19 disease, which has caused significant morbidity and mortality worldwide. A vaccine is crucial to curtail the spread of SARS-CoV-2, while therapeutics will be required to treat ongoing and reemerging infections of SARS-CoV-2 and COVID-19 disease. There are currently no commercially available effective anti-viral therapies for COVID-19, urging the development of novel modalities. Here, we describe a molecular therapy specifically targeted to neutralize SARS-CoV-2, which consists of extracellular vesicles (EVs) containing a novel fusion tetraspanin protein, CD63, embedded within an anti-CoV-2 nanobody. These anti-CoV-2-enriched EVs bind SARS-CoV-2 spike protein at the receptor-binding domain (RBD) site and can functionally neutralize SARS-CoV-2. This work demonstrates an innovative EV-targeting platform that can be employed to target and inhibit the early stages of SARS-CoV-2 infection.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2，简称新冠病毒2）感染会导致冠状病毒病（COVID-19），该病已在全球范围内造成了严重的发病率和死亡率。疫苗对于遏制SARS-CoV-2的传播至关重要，而治疗方法则用于治疗正在发生的以及再次出现的SARS-CoV-2感染和COVID-19疾病。目前尚无用于治疗COVID-19的有效抗病毒疗法，这促使人们开发新的治疗方法。在此，我们描述了一种专门用于中和SARS-CoV-2的分子疗法，该疗法由细胞外囊泡（EVs）组成，这些细胞外囊泡含有一种新型融合四跨膜蛋白CD63，该蛋白嵌入抗新冠病毒2纳米抗体中。这些富含抗新冠病毒2的细胞外囊泡在受体结合域（RBD）位点与SARS-CoV-2刺突蛋白结合，并能在功能上中和SARS-CoV-2。这项工作展示了一个创新的靶向细胞外囊泡平台，可用于靶向和抑制SARS-CoV-2感染的早期阶段。
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