COVID-19: SARS-CoV-2 Neutralizing Agents

COVID-19超级大流行仍因缺乏疫苗或感染控制措施而受到影响 以及缺乏针对这种新病毒的治疗方法。SARS-CoV-2的一个独特特征是 它的R 0 =2.2（感染患者传播疾病的能力），而SARS-CoV的R 0 =1 流感的R 0 =0.3。因此，感染SARS-CoV-2的个人仍然没有症状 但却将病毒传染给家人、朋友和工作中的同事，从而扩大了COVID-19的范围。 例考虑到即将到来的第二波大流行和SARS-CoV-2的潜力， 作为一种季节性病毒，迫切需要开发预防性疫苗和/或疗法（PV/T）， 其可以在病毒在肺中扩增期间和在氧疗期间治疗病毒感染。 该提案通过开发PV/T来应对COVID-19大流行，这将是一个独特的 这种方法以前没有被测试过。这个项目的灵感来自于发现一个特工， 也就是说，一种纳米级10 kDa的壳聚糖，使用专有方法从壳聚糖衍生而来， 常见的饮食补充剂被FDA认为是安全的（GRAS） 称为nanoscale 壳聚糖衍生物（NCD）。NCD 1和其他化学衍生物的合成和测试， 它们通过中和病毒如HIV、呼吸道合胞病毒（RSV）的RNA而具有抗病毒活性， 和科萨基病毒。因此，在初步研究中，9个检查中有5个显示出显著的抗病毒作用。 （80-90%）效果。此外，分子对接研究表明，NCD 1可以与Spike SARS-CoV-2病毒蛋白。最后，我们已经开发了肺靶向纳米医学方法， 将联合收割机NCD 1与Remdesivir联合使用，以提高治疗效果并扩大其预防用途。 根据现有数据，假设NCD本身或与Remdesivir联合使用 将为COVID-19提供出色的PV/T。为了验证这一假设，计划在 预防和治疗环境：非传染性疾病在体外肺上皮细胞中的抗病毒效果 细胞培养（目标1），选择两种最重要的非传染性疾病（有或没有Remdesivir）的有效性， 空气-血液屏障的EpiAlveolar 3D共培养模型（MatTek）（目标#2），以及选择的有效性 在体内小鼠模型中使用或不使用Remdesivir的NCD（目的#3）。 结果将为我们提供 将一种或两种NCD作为单一药物或与Remdesivir联合使用确定为COVID-19 PV/T 方案，这将抑制SARS-CoV-2感染。这些研究的结果将独特地 为COVID-19的预防和治疗做出贡献，并使我们能够 监管部门的批准和未来的临床试验。该小组是独一无二的准备进行这些 学习并拥有适当的专业知识。成功完成拟议的研究是 预计将导致获得临床试验的监管批准。

COVID-19 super pandemic is still suffering from the lack of a vaccine or infection control measures and the lack of any treatments against this new virus. One of the unique features of SARS-CoV-2 is that it has an R0=2.2 (the ability of an infected patient to spread the disease) vs R0=1 for SARS-CoV and R0=0.3 for Influenza. Due to this, individuals infected with SARS-CoV-2 remain asymptomatic and yet pass on the virus to family, friends and colleagues at work, thus expanding the COVID-19 cases. Given the impending second wave of the pandemic and the potential of SARS-CoV-2 being a seasonal virus, there is a dire urgent need to develop prophylactic vaccines and/or therapy (PV/T), which can treat the viral infection during the virus expansion in the lung and during oxygen therapy. This proposal addresses the COVID-19 pandemic by developing a PV/T, which will be a unique approach that has not been tested before. This project is inspired by discovery of a special agent, i.e., a nanoscale 10 kDa chitosan, derived using proprietary methods from chitosan used as a common diet supplement [‘generally regarded as safe’ (GRAS) by FDA] , referred to as nanoscale chitosan derivative (NCD). NCD1 and other chemical derivatives were synthesized and tested for their anti-viral activity by neutralizing RNA of viruses, such as HIV, respiratory syncytial virus (RSV) and Coxsackie virus. Thus, in preliminary studies, 5 out of 9 examined showed significant anti-viral (80-90%) effects. Further, molecular docking studies showed that NCD1 can dock to the Spike protein of SARS-CoV-2 virus. Finally, we have developed lung targeted nanomedicine methods to combine NCD1 with remdesivir for improving treatment efficacy and expanding its use for prevention. Based on data at hand, it is hypothesized that NCDs by themselves or in combination with remdesivir will provide an excellent PV/T against COVID-19. To test this hypothesis, it is planned to examine in both prophylactic and therapeutic settings: the antiviral effectiveness of NCDs in vitro lung epithelial cell cultures (aim #1), the effectiveness of select top two NCDs with or without remdesivir in EpiAlveolar 3D co-culture model (MatTek) of the air-blood barrier (aim #2), and efficacy of select NCD with or without remdesivir in in vivo mouse models (aim #3). The results will provide us in identifying one or two NCDs as a single agent or in combination with remdesivir as COVID-19 PV/T regimen(s), which will inhibit SARS-CoV-2 infection. The results of these studies will uniquely contribute to the repertoire of COVID-19 prophylactics and therapeutics and allow us to move towards regulatory approval and future clinical trials. The team is uniquely poised to conduct these studies and has appropriate expertise. The successful completion of the proposed research is expected to lead to obtaining regulatory approval for a clinical trial.