Project 1: Small Molecule Entry Inhibitors of Pandemic Viruses | Midwest Antiviral Drug Discovery (AViDD) Center

Project 1: Small Molecule Entry Inhibitors of Pandemic Viruses, Virus entry steps. (1) Receptor ACE2 recognition by the spike protein. (2) Refolding of the S2 subunit in the spike protein after the ACE bound S1 subunit is dissociated. (3) Lipid mixing between the host membrane and the viral membrane. This step completes the virus entry, releasing the viral RNA genome into the host cytoplasm to initiate replication. (Koppisetti et al. J. Am. Chem. Soc. 2021, 143, 33, 13205–13211), — Virus entry steps. (1) Receptor ACE2 recognition by the spike protein. (2) Refolding of the S2 subunit in the spike protein after the ACE bound S1 subunit is dissociated. (3) Lipid mixing between the host membrane and the viral membrane. This step completes the virus entry, releasing the viral RNA genome into the host cytoplasm to initiate replication. (Koppisetti et al. J. Am. Chem. Soc. 2021, 143, 33, 13205–13211)

Project Description

In Project 1, we will devise a comprehensive approach to design small molecule compounds that block one of the three key steps to stop virus entry. A combination of structural biology, medicinal chemistry, pharmacological optimization and antiviral studies in animal models will yield a panel of antiviral candidates for the treatment of COVID-19.

The same approach will also be applied to develop antiviral drug candidates for infection by the Ebola virus, Zika virus and Lassa fever virus.

Principal Investigator

ming luo, georgia state university, Project 1: Small Molecule Entry Inhibitors of Pandemic Viruses — **Ming Luo, Ph.D**

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Georgia State University, UT San Antonio Health, University of Iowa, Iowa State University, Nanyang technical university, University of Illinois Chicago, University of Louisville, University of Tennessee, university of Minnesota, UC Berkeley, UC San Diego, UF Scripps Biomedical Research, Baylor, Boston University, New York Blood Center,

Deputy Investigator

Michael Farzan, UF Scripps Biomedical Research, Lab Leak, Covid-19, Project 1: Small Molecule Entry Inhibitors of Pandemic Viruses — ***Michael Farzan, Ph.D***

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Deputy Investigator

Choe Hyeryun, Project 1: Small Molecule Entry Inhibitors of Pandemic Viruses, UF Scripps Biomedical Research — ***Hyeryun Choe, Ph.D***

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Co-Investigators and Other Significant Contributors (OSC)

Fang Li, Ph.D: University of Minnesota, coronavirus research center, spike protein, Midwest AViDD, University of minnesota, llama, lab leak, wuhan, — **Fang Li, Ph.D: University of Minnesota**

*[email protected]*

***Asim Debnath, Ph.D: New York Blood Center, OSC***

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**Lijun Rong, Ph.D: University of Illinois Chicago**

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Lanying Du, Ph.D: Georgia State University, lab leak, covid-19, wuhan — **Lanying Du, Ph.D****: Georgia State University**

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***Irina Gaisana, Ph.D: University of Illinois Chicago***

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**Binghe Wang, Ph.D: Georgia State University**

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**Mukesh Kumar, Ph.D: Georgia State University**

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Norton Peet, Drug Development, University of Nebraska, United States Chemist Society, AstraZeneca — **Norton Peet, Ph.D: Consultant, OSC**