Sagi Shapira - May 13, 2020

Sagi Shapira, PhD, "A functional and genetic link between complement and coagulation functions and SARS-CoV-2 clinical outcome"

Dr. Shapira began his talk with an update to his previous symposium presentation on protein mimicry of viruses in general, with a focus on SARS-CoV-2. His lab is particularly interested in mapping viral-host interactions and has developed P-HISPTer as a tool to match pathogens with their predicted hosts. He then gave a general overview of the viral mimicry and showed that viruses use a structural space that is defined by the host. In particular, RNA viruses utilize structural mimicry much more than DNA viruses and coronaviruses in particular are very adept at protein mimicry. Of the 140 human proteins mimicked by coronaviruses, some are needed for viral entry and replication as expected, but others are surprising such as mimics of complement and coagulation factors which may facilitate phagocytosis of the viral particles. Armed with these predictions, Dr. Shapira’s group next looked at risk factors in a cohort of COVID-19 patients at Columbia and indeed found that macular degeneration, which is associated with hyper-active complement function, was an increased risk factor for intubation and mortality. On the other hand, patients with complement deficient disorders seemed to be protected from development of severe COVID-19, though the numbers of patients here was low. In further support of this finding, he presented a case study on the successful first treatment of a COVID-19 patient with a specific C3 inhibitor which can potentially be used as anti-inflammatory therapy and is now moving to Phase II clinical trials for the treatment of COVID-19.