PROJECT: Working on new sugar-based molecules to suppress the 'cytokine storm’ & excess inflammation that is known to be a very detrimental part of the host response to the corona virus family like SARS-CoV, and predicted for COVID-19
STATUS: Refining syntheses, performing proof of principle/ mechanism experiments in vitro and other pilot safety tests.
PROJECT: Produce synthetic libraries of single-chain antibody fragments (scFvs) and screen against the receptor binding domain (RBD) of the spike protein. We are starting with a mAb with moderate affinity to RBD, and will randomize complementarity determining regions (CDR) 1 and 2 of VHand VL, as well as use V(D)J recombination to randomize the sequence and length of CDR3.
STATUS: Currently constructing the vector to be used for library construction.
PROJECT: 1) The cytokine cascade as it relates to ARDS and 2) receptor recognition and membrane fusion. We have an active collaboration with a company to study a new therapeutic under development that inhibits the cytokine cascade. This work is with live virus in the BSL-3. The second part is a collaboration with Dr. Xin Zhang’s lab focused on the role that integrins and tetraspanins may plan in virus attachment and invasion.
STATUS: Approved BSL-3 protocol, agreements are in place, and experiments with live virus and ARDS mouse models are already ongoing. SARS-CoV-2 infection of A549 and Vero E6 cells is established in BSL3 laboratory and assays with HUMEC's and HMEC's are being investigated. Pseudovirions with SARS-CoV-2 spike proteins are in development.
PROJECT: Express major SARS-CoV-2 structural proteins (Spike protein S and nucleocapsid protein N) for antibody detection and antibody production. Identify inhibitors that may block the interaction of spike protein S with tis receptor ACE2.
STATUS: We have expressed the receptor-binding domain (RBD) as a fusion protein with EGFP tag in E. coli cells and in the process of making spike protein S and nucleocapsid protein N constructs
Zhao, Joe Z.
Cunningham, Madeleine W
PROJECT: Investigating liposome-encapsulated HCQ and Zn to treat COVID-19 by direct lung delivery.
PROJECT: Novel, broad spectrum RNA-virus drug development/cell biology project focused on inhibition of oxysterol-binding protein (OSBP). We are studying and developing a compound named OSW-1, which we think is the first, broad spectrum prophylactic antiviral compound that works through targeting a human protein. We have shown that OSW-1 induces multi-log reduction of several different RNA viruses (i.e., enteroviruses, rhinoviruses, coxsackie viruses) at low nanomolar concentrations.
STATUS:Shown that OSW-1-compound drops feline coronavirus 3-4 log folds at low nanomolar concentrations. Testing against human CoV soon, including SARS-CoV-2 in a few weeks/months.