A protease activity profiling strategy to inhibit cell-to-cell transmission of SARS-CoV-2

SARS-CoV-2是一种新型冠状病毒，于2019年底出现，已经在中国感染了数万人，现在已经蔓延到40个国家。为了打破传播链，需要确定增加SARS-CoV-2传播性的宿主和病毒决定因素，以便制定适当和有效的干预措施。病毒传播的两个主要决定因素是宿主细胞蛋白酶，它可以切割病毒刺突蛋白，使其更具传染性，而病毒刺突本身已经进化到携带额外的蛋白酶切割位点，允许宿主扩展。我们的目标是识别这些细胞蛋白酶并抑制它们以阻止病毒传播。我们的目标是产生带有不能被切割的刺突蛋白的病毒，以确定我们是否能阻止它们的传播。总的来说，这些方法将用于指导治疗性分子（针对蛋白酶）的生产和疫苗（针对病毒刺突）的设计。

SARS-CoV-2 is a new coronavirus, which emerged in late 2019, has infected tens of thousands in China, and has now spread into 40 countries. To break the chain of transmission, host and viral determinants that increase the transmissability of SARS-CoV-2 need to be identified, in order to develope suitable and effective intervnetions. Two main determinants of virus transmission are the host cellular proteases that cleave the viral Spike protein to make it more infectious, and the viral Spiek itself that has evolved to carry additional protease-cleavage sites, allowing host expansion. We aim to identify these cellular proteases and inhibit them to block virus transmission. We also aim to generate virus with Spike proteins that cannot be cleaved, to determine whether we can arrest their spread. Collectively these approaches will be used to inform production of therapeutic molecules (against the proteases) and design of vaccines (against the viral Spike).