Debulking SARS-CoV-2 in saliva using angiotensin converting enzyme 2 in chewing gum to decrease oral virus transmission and infection.
Debulking SARS-CoV-2 in saliva using angiotensin converting enzyme 2 in chewing gum to decrease oral virus transmission and infection.
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DOI：
10.1016/j.ymthe.2021.11.008
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发表时间：
2022-05-04
期刊：
影响因子：
--
通讯作者：
Collman RG
中科院分区：
文献类型：
--
作者：
Daniell H;Nair SK;Esmaeili N;Wakade G;Shahid N;Ganesan PK;Islam MR;Shepley-McTaggart A;Feng S;Gary EN;Ali AR;Nuth M;Cruz SN;Graham-Wooten J;Streatfield SJ;Montoya-Lopez R;Kaznica P;Mawson M;Green BJ;Ricciardi R;Milone M;Harty RN;Wang P;Weiner DB;Margulies KB;Collman RG
为了提出在口腔中抑制病毒的新概念，病毒复制的主要位点，病毒捕获蛋白CTB-ACE2在叶绿体中表达，并开发了临床级植物材料，以满足FDA的要求。含有CTB-ACE2的植物细胞的口香糖（2g）表达高达17.2 mg ACE2/g干重（11.7%叶蛋白），具有与常规口香糖相同的物理特性和味道/风味，并且在口香糖压缩过程中没有蛋白质损失。通过荧光素酶或红色荧光测定，ccb - ace2胶有效（>95%）抑制慢病毒刺突或vsv刺突假病毒进入Vero/CHO细胞。通过微泡（飞摩尔浓度）或qPCR评估，CTB-ACE2微粒的孵卵使COVID-19拭子/唾液样本中的SARS-CoV-2病毒计数减少了95%，表明病毒捕获和阻断了细胞进入。与健康个体相比，COVID-19唾液样本显示较低或无法检测到ACE2活性（2,582对50,126 ΔRFU； 27对225酶单位），证实感染患者对病毒进入的易感性更高。CTB-ACE2活性被SARS-CoV-2受体结合域预孵育完全抑制，这可能解释了COVID-19患者唾液ACE2活性降低的原因。含有病毒捕获蛋白的口香糖提供了一种普遍负担得起的策略，可以通过减少或减少向他人传播来保护患者免受大多数口腔病毒的再次感染。由于全球绝大多数人口未接种疫苗，并且病毒载量较高的变体爆发，需要新的方法来减少SARS-CoV-2的传播和感染。daniel等人报道，口香糖中含有表达血管紧张素转换酶2的植物细胞，可以有效地捕获COVID-19患者唾液或拭子样本中的SARS-CoV-2。
To advance a novel concept of debulking virus in the oral cavity, the primary site of viral replication, virus-trapping proteins CTB-ACE2 were expressed in chloroplasts and clinical-grade plant material was developed to meet FDA requirements. Chewing gum (2 g) containing plant cells expressed CTB-ACE2 up to 17.2 mg ACE2/g dry weight (11.7% leaf protein), have physical characteristics and taste/flavor like conventional gums, and no protein was lost during gum compression. CTB-ACE2 gum efficiently (>95%) inhibited entry of lentivirus spike or VSV-spike pseudovirus into Vero/CHO cells when quantified by luciferase or red fluorescence. Incubation of CTB-ACE2 microparticles reduced SARS-CoV-2 virus count in COVID-19 swab/saliva samples by >95% when evaluated by microbubbles (femtomolar concentration) or qPCR, demonstrating both virus trapping and blocking of cellular entry. COVID-19 saliva samples showed low or undetectable ACE2 activity when compared with healthy individuals (2,582 versus 50,126 ΔRFU; 27 versus 225 enzyme units), confirming greater susceptibility of infected patients for viral entry. CTB-ACE2 activity was completely inhibited by pre-incubation with SARS-CoV-2 receptor-binding domain, offering an explanation for reduced saliva ACE2 activity among COVID-19 patients. Chewing gum with virus-trapping proteins offers a general affordable strategy to protect patients from most oral virus re-infections through debulking or minimizing transmission to others. With a large majority of the global population unvaccinated and outbreaks of variants with higher viral load, new methods are needed to decrease SARS-CoV-2 transmission and infection. Daniell et al. report that chewing gum containing plant cells expressing angiotensin-converting enzyme 2 efficiently traps SARS-CoV-2 in COVID-19 patient saliva or swab samples.
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作者：
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通讯作者：
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DOI：
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