Development of a SARS-CoV-2 spike protein binding assay using human epithelial cells for COVID-19 therapy discovery and development

当前COVID-19大流行的紧迫性需要尽快和尽可能安全地开发新的治疗方法。参与这些工作的许多实验室得出的任何结果都需要以各种方式进行测试，以帮助我们了解它们是否适用于可能感染SARS-CoV-2（导致COVID-19的病毒）的人。病毒要引起这种疾病，它需要进入我们的一些细胞，在那里它可以生存、繁殖，然后感染体内的其他细胞。要做到这一点，病毒首先需要锁定我们的细胞。为此，它使用病毒外部的特定部分“刺突”，将其固定在细胞外部的特殊部分（“受体”）上，就像钥匙能锁上锁一样。该项目将概括病毒感染的第一个关键步骤，使我们能够在“培养皿”中测试新的治疗方法，以支持针对COVID-19的治疗发现工作。虽然支持这一发展的模型可以使用含有纯化细胞成分的系统（使用病毒用于进入的“受体”），或者使用完整的病毒，但缺乏可以以简单的方式用于测试药物和疫苗接种产生的抗体对病毒进入人类细胞的特定步骤的影响的细胞模型。我们打算开发一种“基于细胞”的模型，使用人类细胞（包括肺部细胞，已知这是病毒进入的关键部位）和SARS-CoV-2纯化的刺突蛋白。这种生物模型将使我们和我们的工业合作伙伴能够在病毒感染的一个非常重要的特定步骤上测试他们的治疗方法。我们将使用先进的成像技术来可视化病毒刺突蛋白与人类细胞的结合，然后我们将能够测试药物或其他药物（如疫苗产生的抗体）如何影响病毒进入的这一特定步骤。然后，这将使候选药物能够被选择作为治疗药物，开发药物的改进版本或支持选择产生针对病毒的保护性抗体的疫苗。

The urgency of the current COVID-19 pandemic needs new treatments to be developed as quickly and as safely as possible. Whatever comes out of the many labs involved in these efforts needs to be tested in a variety of ways to help us know if they will work when given to people who might be infected by SARS-CoV-2, the virus which causes COVID-19\. For the virus to cause this disease, it needs to get inside some of our cells where it can survive, multiply and then infect other cells in the body. To do this, the virus first needs to latch onto our cells. For this, it uses a specific part on the outside of the virus, the 'spike', to fasten onto special parts on the outside of our cells ('receptors') to which if fits, like a key fits a lock.This project will recapitulate this first essential step of viral infection allowing us to test new treatments 'in a dish' in order to support the therapeutic discovery effort against COVID-19\. Whilst models to support this development are available using systems with purified components of cells (using the 'receptors' the virus uses for entry), or, using the intact virus, there is a lack of cellular models that can be used in a simple manner for testing the impact of drugs, and antibodies arising from vaccination, on specific steps of viral entry into human cells. We intend to develop a 'cell-based' model using human cells (including cells lining the lung, which are known to be a key site of entry for the virus) and SARS-CoV-2 purified spike protein. This biological model will enable us and our industrial partners to test their therapeutics on a very specific step vital for viral infection. We will use advanced imaging techniques to visualise this binding of the viral spike protein to human cells, and, we will then be able to test how drugs, or other agents such as antibodies generated by a vaccine, impact this specific step of viral entry. This will then enable candidate drugs to be selected as therapeutics, improved versions of drugs to be developed or support the selection of vaccines that generate protective antibodies against the virus.