Altamira Medica AG, 6300 Zug, Switzerland.
Texcell SA, 91000 Evry, France.
Int J Mol Sci. 2022 Apr 6;23(7):4062. doi: 10.3390/ijms23074062.
The nasal epithelium is a key portal for infection by respiratory viruses such as SARS-CoV-2 and represents an important target for prophylactic and therapeutic interventions. In the present study, we test the safety and efficacy of a newly developed nasal spray (AM-301, marketed as Bentrio) against infection by SARS-CoV-2 and its Delta variant on an in vitro 3D-model of the primary human nasal airway epithelium. Safety was assessed in assays for tight junction integrity, cytotoxicity and cilia beating frequency. Efficacy against SARS-CoV-2 infection was evaluated in pre-viral load and post-viral load application on airway epithelium. No toxic effects of AM-301 on the nasal epithelium were found. Prophylactic treatment with AM-301 significantly reduced viral titer vs. controls over 4 days, reaching a maximum reduction of 99% in case of infection from the wild-type SARS-CoV-2 variant and more than 83% in case of the Delta variant. When AM-301 administration was started 24 h after infection, viral titer was reduced by about 12-folds and 3-folds on Day 4. The results suggest that AM-301 is safe and significantly decelerates SARS-CoV-2 replication in cell culture inhibition assays of prophylaxis (pre-viral load application) and mitigation (post-viral load application). Its physical (non-pharmaceutical) mechanism of action, safety and efficacy warrant additional investigations both in vitro and in vivo for safety and efficacy against a broad spectrum of airborne viruses and allergens.
鼻上皮是呼吸道病毒（如 SARS-CoV-2）感染的关键门户，是预防和治疗干预的重要靶点。在本研究中，我们测试了一种新开发的鼻腔喷雾剂（AM-301，以 Bentrio 销售）对 SARS-CoV-2 及其 Delta 变体在体外原代人鼻气道上皮 3D 模型中的感染的安全性和疗效。安全性通过紧密连接完整性、细胞毒性和纤毛跳动频率测定来评估。在气道上皮前病毒负荷和后病毒负荷应用中评估了对 SARS-CoV-2 感染的疗效。未发现 AM-301 对鼻上皮有任何毒性作用。与对照组相比，预防性应用 AM-301 可显著降低病毒滴度，在野生型 SARS-CoV-2 变体感染的情况下，最大降低幅度为 99%，在 Delta 变体感染的情况下，最大降低幅度超过 83%。当在感染后 24 小时开始 AM-301 给药时，在第 4 天，病毒滴度降低了约 12 倍和 3 倍。结果表明，AM-301 是安全的，可显著减缓 SARS-CoV-2 在细胞培养抑制试验中的复制（前病毒负荷应用）和缓解（后病毒负荷应用）。其物理（非药物）作用机制、安全性和疗效值得进一步在体外和体内进行研究，以评估其对广谱空气传播病毒和过敏原的安全性和疗效。
