SARS-CoV-2 & Other Coronaviruses

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Rationale

During the COVID-19 pandemic, we utilized our expertise in structural biology to characterize the main protease of Severe Acute Respiratory Sydrome Coronavirus 2 (SARS-CoV-2). We are analyzing protease variants bearing potential resistance mutations alongside proteases from other species of coronaviruses to support future pandemic preparedness.

What we're doing

In addition to characterizing the interaction of promising antibodies that can neutralize the virus, we focused on the main protease of SARS-CoV-2 as a drug target. Our most recent efforts include collaborations with Novartis (NBIR) and the Moonshot consortium to understand the evolution of resistance and to design robust antiviral drugs.

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Publication Highlights

Ejemel M, Li Q, Hou S, Schiller ZA, Tree JA, Wallace A, Amcheslavsky A, Kurt Yilmaz N, Buttigieg KR, Elmore MJ, Godwin K, Coombes N, Toomey JR, Schneider R, Ramchetty AS, Close BJ, Chen DY, Conway HL, Saeed M, Ganesa C, Carroll MW, Cavacini LA, Klempner MS, Schiffer CA, Wang Y. “A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction” Nature Communications, Vol. 11, Iss. 1, 4198 (2020).

Shaqra AM, Zvornicanin SN, Huang QYJ, Lockbaum GJ, Knapp M, Tandeske L, Bakan DT, Flynn J, Bolon DNA, Moquin S, Dovala D, Kurt Yilmaz N*, Schiffer CA*. “Defining the substrate envelope of SARS-CoV-2 main protease to predict and avoid drug resistance” Nature Communications, Vol. 13, 3556 (2022). (*joint corresponding author)

Flynn JM, Samant N, Schneider-Nachum G, Barkan DT, Kurt Yilmaz N, Schiffer CA, Moquin SA, Dovala D, Bolon DNA. “Comprehensive fitness landscape of SARS-CoV-2 Mpro reveals insights into viral resistance mechanisms” Elife, Vol. 11, e77433 (2022).

Zvornicanin SN, Shaqra AM, Huang QJ, Ornelas E, Moghe M, Knapp M, Moquin S, Dovala D, Schiffer CA, Kurt Yilmaz N*. “Crystal Structures of Inhibitor-Bound Main Protease from Delta- and Gamma-Coronaviruses” Viruses, Vol. 15, Iss. 3, 781 (2023).