SARS-CoV-2 work in the Mühlberger lab

Members of the Mühlberger lab are highly experienced in working with emerging infectious viruses, including Ebola virus, Marburg virus, and SARS-coronavirus. We are using our expertise in virology to help contain the COVID-19 outbreak. We do this jointly with investigators from other research areas to develop innovative countermeasures against SARS-CoV-2. Collaborative efforts have already been set up with research labs at BU, the Ragon Institute, HMS, MIT, UMass Worcester, and UConn. This work is supported by MassCPR, Fast Grants, and CTSI. Thank you!

What have we done so far?

We have started to work on SARS-CoV-2 in March 2020. We do what we do best  – infect cells with nasty viruses. Our infection platforms can be used by other researchers for their specific assays with the goal to find countermeasures against SARS-CoV-2. Applications by our collaborators include  the use of iPSC-derived human cells as infection platforms for SARS-CoV-2, proteomics and transcriptomics studies, profiling immune response signatures, and repurposing  approved therapeutics to inhibit SARS-CoV-2 infection.

Watch the poster video!

Adam and Jessie explain everything you need to know about SARS-CoV-2 infection of iAT2 cells (see also paper Huang et al., 2020).

 

SARS-C0V-2 papers (Mühlberger lab members highlighted in blue)

Amraie, R., Yin, W., Napoleon, M.A., Suder, E., Berrigan, J., Zhao, G., Olejnik, J., Chandler, K., Xia, C., Feldman, J., Hauser, B., Caradonna, T., Schmidt, A., Gummuluru, S., Mühlberger, E., Chitalia, V., Costello, C., and Rahimi, N., 2021. CD209L/L-SIGN and CD209/DC-SIGN act as receptors for SARS-CoV-2. ACS Central Science, accepted.

Mithal, A.*, Hume, A. J.*, Lindstrom-Vautrin, J., Villacorta-Martin, C., Olejnik, J., Bullitt, E., Hinds, A., Mühlberger, E.#, and Mostoslavsky, G.# Human pluripotent stem cell derived intestinal organoids model SARS-CoV-2 infection revealing a common epithelial inflammatory response. Stem Cell Reports, 2021. 16(4): 940-953. PMID: 33852884. *equal contribution; #corresponding authors.

Huang, J.*, Hume, A. J.*, Abo, K. M.*, Werder, R. B.*, Villacorta-Martin, C., Alysandratos K.-D., Beermann, M. L., Simone-Roach, C., Olejnik, J., Suder, E. L., Bullitt, E., Hinds, A., Sharma, A., Bosmann, M., Wang, R., Hawkins, F., Burks, E. J., Saeed, M., Wilson, A. A.#, Mühlberger, E.#, and Kotton, D. N.#  SARS-CoV-2 infection of pluripotent stem cell-derived human lung alveolar type 2 cells elicits a rapid epithelial-intrinsic inflammatory response. Cell Stem Cell, 2020. 27(6): 962-973.e7. PMID: 32979316. *equal contribution; #corresponding authors.

Hekman, R. M.*, Hume, A. J.*, Goel R. K.*, Abo, K. M.*, Huang, J.*, Blum, B. C.*, Werder, R. B.*, Suder, E. L.*, Paul, I.*, Phanse, S., Youssef, A., Alysandratos, K. D., Padhorny, D., Ojha, S., Patten, J. J., Villacorta-Martin, C., Bolzan, D., Perea-Resa, C., Bullitt, E., Hinds, A., Tilston-Lunel, A., Varelas, X., Braunschweig, U., Kwan, J. H., McComb, M., Basu, A., Saeed, M., Perissi, V., Burks, E. J., Wolozin, B. L., Layne, M. D., Blencowe, B. J., Wuchty, S., Lyons, S. M., Kozakov, D., Cifuentes, D., Connor, J. H., Davey, R., Blower, M., Kotton, D. N.#, Wilson, A. A.#, Mühlberger, E.#, Andrew Emili, A. Actionable Cytopathogenic Host Responses of Human Lung Alveolar Type 2 Cells to SARS-CoV-2 Infection. Molecular Cell, 2021. 81(1): 212. PMID: 33259812. *equal contribution; #corresponding authors.

Luban J.*, Sattler R.*, Mühlberger E.*, Graci JD, Cao L, Weetall M, Trotta C, Colacino JM, Bavari S, Strambio-De-Castillia C, Suder EL, Wang Y, Soloveva V, Cintron-Lue K, Naryshkin NA, Pykett M, Welch EM, O’Keefe K, Kong R, Goodwin E, Jacobson A, Paessler S, Peltz S. 2020. The DHODH Inhibitor PTC299 Arrests SARS-CoV-2 Replication and Suppresses Induction of Inflammatory Cytokines.Virus Res, 2020. N292: 198246. PMID: 33249060. *equal contribution.

Manuscripts posted on BioRxiv

Gao, C., Zeng, J., Jia, N., Stavenhagen, K., Matsumoto, Y., Zhang, H., Li, J., Hume, A.J., Mühlberger, E., van Die, I., Kwan, J., Tantisira, K., Emili, A., Cummings, R.D., 2020. SARS-CoV-2 Spike Protein Interacts with Multiple Innate Immune Receptors. bioRxiv.

 

Immunofluorescence is a great tool to discriminate between infected and non-infected cells. The cells on the left are infected with SARS-CoV-2 and stained with an antibody against the viral nucleoprotein (green) and an antibody against double-stranded (ds) RNA (red). The nuclei are stained with DAPI (blue). Using this tool, it is easy to find out if cells are permissive to SARS-CoV-2 infection. Shown on the right hand side are various cells lines infected with SARS-CoV-2. Only green cells are infected. Red, tubulin. Performed by Ellen Suder.

It helps to know what the virus does to the infected cells.

This is an electron micrograph of an iPSC-derived type 2 alveolar lung cell infected with SARS-CoV-2. This cell type is infected in severe cases of COVID-19. The white arrows indicate SARS-CoV-2 particles. The cells were provided by the Kotton and Wilson labs at BU, CReM. The infection was performed by Adam Hume. Electron microscopy was performed by Anne Hinds, Pulmonary Center and Esther Bullitt, Dept. of Physiology and Biophysics.

In your face, coronavirus!

Here, we infected Vero E6 cells with SARS-CoV-2 and treated the infected cells with a promising antiviral drug candidate provided by a collaborator. The cells were fixed and stained with an antibody against the viral nucleoprotein (green). This compound clearly blocks SARS-CoV-2 replication and is now tested in Phase 2/3 clinical trials. Good news for us. Bad news for COVID-19. Performed by Ellen Suder.