A COMPARATIVE ANALYSIS OF SARS-COV-2 ANTIVIRALS CHARACTERIZES 3CLPRO INHIBITOR PF-00835231 AS A POTENTIAL NEW TREATMENT FOR COVID-19
February 23, 2021
de Vries M., Mohamed A.S., Prescott R.A., Valero-Jimenez A.M., Desvignes L., O'Connor R., Steppan C., Devlin J.C., Ivanova E., Herrera A., Schinlever A., Loose P., Ruggles K., Koralov S.B., Anderson A.S., Binder J., and Dittmann M. (2021), "A comparative analysis of SARS-CoV-2 antivirals characterizes 3CLpro inhibitor PF-00835231 as a potential new treatment for COVID-19" J. Virol. DOI: 10.1128/JVI.01819-20
We characterize the first-in-class protease inhibitor for SARS-CoV-2 currently in clinical trials.
TYPE I INTERFERON SUSCEPTIBILITY DISTINGUISHES SARS-COV-2 FROM SARS-COV
November 9 , 2020
Lokugamage K.G., Hage A., de Vries M., Valero-Jimenez A.M., Schindewolf C., Dittmann M.,Rajsbaum R., Menachery V.D., "Type I Interferon Susceptibility Distinguishes SARS-CoV-2 from SARS-CoV", J Virol. 2020 Nov 9;94(23)
Together with Dr. Vineet Menachery and Dr. Ricardo Rajsbaum's lab, we show that while SARS-CoV potently escapes both innate immune detection and the consequences of IFN signaling, SARS-CoV-2 has lost its ability to escape the effects of IFN.
THE ETS TRANSCRIPTION FACTOR ELF1 REGULATES A BROADLY ANTIVIRAL PROGRAM DISTINCT FROM THE TYPE I INTERFERON RESPONSE
November 04, 2019
Seifert LL*, Si C*, Saha D, Sadic M, de Vries M, Ballentine S, Briley A, Wang G, Valero-Jimenez A, Mohamed A, Schaefer U, Moulton H, García-Sastre A, Tripathi S, Rosenberg BR, Dittmann M, The regulatory factor ELF1 triggers a critical wave of transcription in the antiviral response to type I interferon (2019), PLOS Pathogens, doi.org/10.1371/journal.ppat.1007634
We show that the transcription factor ELF1 provides an additional layer of the innate host response, independent from the action of type I interferons.
ATP-DEPENDENT EFFECTOR-LIKE FUNCTIONS
OF RIG-I-LIKE RECEPTORS
April 16, 2015
Yao H.*, Dittmann M.*, Peisley A., Hoffmann H.-H., Gilmore R.H., Schmidt T., Schmidt-Burgk J., Hornung V., Rice C.M. & Hur S. “ATP-dependent effector-like functions of RIG-I like receptors” (2015), Mol. Cell 58: 541-548 (* = equal contributions)
We demonstrate that RIG-I and MDA5 not only function as viral RNA receptors, but also as effector proteins by displacing viral proteins bound to RNA during ATP hydrolysis. Accordingly, RIGI/MDA5 can suppress viral replication independent of the interferon signaling.
A SERPIN SHAPES THE EXTRACELLULAR ENVIRONMENT TO PREVENT
INFLUENZA A VIRUS MATURATION
February 12, 2015
Dittmann, M., Hoffmann, H.-H., Scull, M. A., Gilmore, R.H., Bell, K.L., Ciancanelli, M., Wilson, S.J., Crotta, S., Yu, Y., Flatley, B., Xiao, J.W., Casanova, J.-L., Wack, A., Bieniasz, P.D. & Rice, C.M. “A serpin shapes the extracellular environment to prevent influenza A virus maturation” (2015), Cell 160: 631–643
Plasminogen activator inhibitor (PAI-1) blocks surface glycoprotein maturation of influenza A virus, thus reducing virus spread in the airways and revealing that the innate immune system, driven by type I IFN, uses modulation of the extracellular environment to inhibit viruses.
A COMPLEX WEB OF HOST DEFENSES
January 25, 2014
Schneider, W.M., Dittmann Chevillotte, M.& Rice, C.M. “Interferon-stimulated genes: a complex web of host defences” (2014), Ann. Rev. Immunol. 32: 513-545
Interferon-stimulated gene (ISG) products take on a number of diverse roles. Collectively, they are highly effective at resisting and controlling pathogens. In this review, we begin by introducing interferon (IFN) and the JAK-STAT signaling pathway to highlight features that impact ISG production. Next, we describe ways in which ISGs both enhance innate pathogen-sensing capabilities and negatively regulate signaling through the JAK-STAT pathway. Several ISGs that directly inhibit virus infection are described with an emphasis on those that impact early and late stages of the virus life cycle. Finally, we describe ongoing efforts to identify and characterize antiviral ISGs, and we provide a forward-looking perspective on the ISG landscape.