Modern approaches for developing antivirals against SARS-CoV 2

The SARS-CoV-2 pandemic has become an unprecedented burden to public health, our civil societies and the global economy. To provide frontline therapies for COVID-19 and future corona virus outbreaks requires a concerted effort of different disciplines, technologies, high security labs, and rapid translation of scientific findings to highly innovative and 'Äúhungry'Äù SME partners. For the MAD-CoV-2 project we have assembled a multidisciplinary team of world-leading researchers and innovative industry partners to unlock the Achille'Äôs heels of the virus infections in host cells and rapidly translate such knowledge into disruptive new medicines and public health measures. Our team members have been on the ground of the first SARS and Ebola outbreaks, head containment facilities to study highly infectious viruses, are world-leading in engineering human tissues, developed breakthrough technologies that allow us to find host factors for viral infections at unmatched speed and resolution, and discovered ACE2 and made the first in vivo link between ACE2, SARS, and lung injury, leading to rational drug development which is imminent to be tested in European COVID-19 patients. ACE2 is also the key receptor for SARS-CoV-2 Spike protein and has got centre stage for novel therapies and a fundamental understanding of COVID-19. The aims of MAD-CoV-2 are 1. to engineer human tissues to test novel therapies and vaccines; 2. to provide critical evidence on the role of clinical grade ACE2 in viral replication and COVID-19 pathogenesis; 3. to perform high-throughput screens to genetically map, at a single amino acid resolution, essential host factor that are critical for SARS-CoV-2 replication; and 4. to rapidly translate this knowledge into novel therapies to fight the current and, importantly, future corona virus outbreaks. Our data and unique tissue reagents will be made available to the entire community for drug testing and development, supporting all other efforts.