VIRTACs - Protein Degradation as an Anti-Viral Strategy

正如当前的新型冠状病毒疫情所强调的那样，病毒是对人类健康和繁荣的持续威胁。病毒感染每年导致数百万人死亡，人口增长、国际旅行和气候变化意味着人类越来越容易受到新出现的病毒威胁的影响。除了病毒引起的严重发病率和死亡率之外，生产力损失和牲畜死亡意味着病毒对全球经济造成相当大的负担（估计每年全球数百亿英镑）。正如许多组织，包括联合国、世界卫生组织和英国政府所认识到的那样，制定新的战略来对抗病毒威胁是非常重要的。大多数抗病毒药物通过经典机制起作用，该机制涉及药物与其靶标的1：1相互作用。药物化学中的一种新兴策略试图使用称为蛋白质降解的新机制来克服这种“基于占用”的限制。蛋白质降解方法有很多潜在的优势，但它足够新，在抗病毒方面还没有真正探索过。该项目将探索针对3种对人类健康具有重要意义的病毒的蛋白质降解机制：艾滋病毒，流感和导致当前Covid-19大流行的SARS-CoV-2病毒。虽然我们的目标不是在这个项目期间产生一种新药（这需要更长的时间和更高的成本），但我们相信这个项目将为未来重要的新疗法奠定基础。毫无疑问，这些疗法将是必要的，因为病毒正在不断发展耐药性。

As highlighted by the current Covid-19 pandemic, viruses are a constant threat to human health and prosperity. Viral infections kill millions of people every year and population growth, international travel and climate change mean that human populations are increasingly vulnerable to emerging viral threats. Further to the severe morbidity and mortality caused by viruses, lost productivity and livestock deaths mean viruses place a considerable burden on the global economy (estimated in the tens of billions of pounds worldwide each year). Developing new strategies to combat viral threats is of tremendous importance, as recognized by many organizations including the United Nations, World Health Organization, and UK Government. Most antiviral drugs work through a classical mechanism that involves a 1:1 interaction of the drug with its target. An emerging strategy in Medicinal Chemistry seeks to overcome this "occupancy based" limitation using a new mechanism called protein degradation. There are lots of potential advantages to the protein degradation approach, but its new enough that it hasn't really been explored much in an antiviral context. This project will explore the protein degradation mechanism in targeting 3 viruses of importance to human health: HIV, influenza, and the SARS-CoV-2 virus that is causing the current Covid-19 pandemic. Although we're not aiming to generate a new drug during this project period (that takes longer and costs more), we believe that this project will lay the groundwork for important new therapies in the future. There's no doubt that these therapies will be needed, as viruses are constantly developing resistance.