COVID-19: SARS-CoV-2 Neutralizing Agents

新冠肺炎超级大流行仍在苦于缺乏疫苗或感染控制措施 以及缺乏任何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R0=2.2(感染患者传播疾病的能力)与SARS-CoV的R0=1 流感的R0=0.3。因此，感染SARS-CoV-2病毒的人仍然没有症状 但又会将病毒传递给家人、朋友和同事，从而扩大了新冠肺炎 案子。鉴于迫在眉睫的第二波大流行以及SARS-CoV-2可能成为 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)， 它可以治疗病毒在肺内扩张和氧疗期间的病毒感染。 这项建议通过开发一种PV/T来应对新冠肺炎大流行，这将是一种独特的 这是一种以前没有经过测试的方法。这个项目的灵感来自于一名特工的发现， 即纳米级的10 kDa壳聚糖，使用专利方法从用作 普通膳食补充剂[FDA普遍认为安全的(GRAS)] ，被称为纳米级 壳聚糖衍生物(NCD)合成了NCD1和其他化学衍生物，并对其进行了测试 它们通过中和HIV、呼吸道合胞病毒(RSV)等病毒的RNA而具有抗病毒活性。 和柯萨奇病毒。因此，在初步研究中，接受检查的9人中有5人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，NCD1可以对接到Spike SARS-CoV-2病毒的蛋白。最后，我们开发了肺靶向纳米医学方法来 将NCD1与雷米昔韦联合使用，以提高治疗效果，扩大其预防用途。 根据手头的数据，假设非传染性疾病本身或与RESENDVE相结合 将对新冠肺炎提供出色的PV/T。为了检验这一假设，计划在 预防和治疗环境：NCDS在体外肺上皮细胞的抗病毒作用 细胞培养(目标1)，选择前两种非传染性疾病的有效性 气-血屏障的肺泡表面3D共培养模型(MATTEK)(目标2)和SELECT的疗效 在活体小鼠模型中使用或不使用瑞昔维韦的NCD(目标3)。 结果将为我们提供 将一种或两种非传染性疾病作为单一药物或与雷米替韦联合识别为新冠肺炎PV/T 方案(S)，这将抑制SARS-CoV-2感染。这些研究结果将是独一无二的 贡献新冠肺炎预防和治疗曲目，让我们行动起来 朝向监管批准和未来的临床试验。该团队正独一无二地准备进行这些 学习并具有适当的专业知识。成功完成拟议的研究是 预计将导致临床试验获得监管部门的批准。

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.