聚维酮碘原位凝胶形成液体外灭活SARS-Cov-2的研究

Bo Liang, Xudong Yuan, Gang Wei, Wen Wang, Ming Zhang, Peng Haizhou, Juan Carlos Hernaiz-Leonardo, A. Javer, M. Mendenhall, Justin Jul, er, Sammi Huang, H. Michail, Yong Lu, Qianming Zhu, J. Baldwin
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引用次数: 1

摘要

背景:聚维酮碘(PVP-I)鼻液对SARS-CoV-2病毒有效,但从鼻腔中被迅速清除,限制了其使用。PVP-I凝胶形成溶液可以避免这个问题,因为它们具有更高的粘度和较长的清除时间。目的:研究采用原位凝胶形成技术制备的长效PVP-I组合物对SARS-CoV-2病毒的体外杀病毒活性,并在大鼠模型上验证其安全性。方法:我们测试了不同稀释度的PVP-I凝胶形成溶液——满浓度、90%、50%、28%和9%的原始配方浓度——在不同的暴露时间,以评估感染VERO76细胞对SARSCoV- 2的病毒杀灭活性。与病毒对照相比,经配方处理的测试井中病毒的减少量作为对数减少值记录了病毒杀灭活性。我们使用Sprague Dawley CD®IGS大鼠进行了为期28天的毒性研究,以确定PVP-I制剂的潜在延迟毒性。结果:PVP-I凝胶型鼻喷雾剂能快速灭活SARS-CoV-2,抑制病毒对VERO76细胞的感染。未观察到PVP-I制剂的毒性。用最低浓度的PVP-I制剂对病毒进行预孵育,发现病毒显著失活。在我们的动物模型中未观察到延迟毒性。结论:PVP-I凝胶形成制剂在体外暴露30秒内灭活SARS-CoV-2,暴露时间越长效果越明显。这些配方可能在临床环境中对管理SARS-CoV-2感染患者有用。
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In vitro Inactivation of SARS-Cov-2 by Povidone-Iodine In situ Gel FormingSolution
Background: Povidone Iodine (PVP-I) nasal solutions are effective against the SARS-CoV-2 virus, but are cleared rapidly from the nasal cavity, limiting its use. PVP-I gel forming solutions can circumvent this problem due to their higher viscosity and prolonged clearing time. Objective: Characterize the in vitro virucidal activity of long-acting PVP-I compositions developed using an in situ gel forming technology against the SARS-CoV-2 virus and test its safety using a rat model. Methods: We tested different dilutions of the PVP-I gel forming solution– full concentration, 90%, 50%, 28% and 9% of the original formulation concentration – at varying exposure times to assess virucidal activity against SARSCoV- 2 in VERO76 cells infected. Virucidal activity was recorded as the reduction of virus in formulation-treated test wells compared to virus controls as a log reduction value. We conducted a 28-day toxicity study using Sprague Dawley CD® IGS rats to determine the potential delayed toxicity of a PVP-I formulation. Results: The PVP-I gel-forming nasal spray rapidly inactivated SARS-CoV-2, inhibiting the viral infection of VERO76 cells. No toxicity was observed for the PVP-I formulations. Significant inactivation was noted with preincubation of the virus with this PVP-I formulation at the lowest concentrations tested. No delayed toxicity was observed in our animal model. Conclusions: PVP-I gel forming formulations inactivate SARS-CoV-2 in vitro within 30 seconds of exposure, with increasing effects seen at higher exposure times. These formulations could prove useful in a clinical setting for managing SARS-CoV-2 infected patients.
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