FOR-COVID

Bavarian consortium for research on the pandemic disease COVID-19 (FOR-COVID)

Decoding the biology of SARS-CoV-2 infections from its direct in vivo RNA-protein interactome

Projectleaders
Prof. Dr. Jörg Vogel
Dr. Mathias Munschauer

2019, the ongoing coronavirus disease 2019 (COVID-19) pandemic has resulted in unprecedented socioeconomical disruptions and more than 4 million lives lost worldwide. Despite the urgent need for effective antiviral therapies, we still do not fully understand the molecular basis of SARS-CoV-2 infection and pathogenesis. Characterizing the interactions that SARSCoV- 2 viral RNAs make with host cell proteins during infection can improve our understanding of viral RNA functions and the host innate immune response. During the first funding period, we published a pioneering study that resolved how SARS-CoV-2 RNAs interact with the host cell proteome. We identified more than 100 human proteins that specifically bind to SARS-CoV-2 RNA, mapped their direct RNA contact sites, and demonstrated the functional importance of several of these viral RNA binders for SARS-CoV-2 infections. In the next funding period, we aim to expand these foundational insights by mechanistically dissecting how the newly discovered antiviral RNA-binding protein CNBP functions, and elucidating whether CNBP can be harnessed as a therapeutic target. We will then focus on identifying molecular vulnerabilities of SARS-CoV-2 by resolving the interactions of double-stranded viral RNA, which will yield host proteins directly involved in viral RNA sensing and targeting. Connecting biochemical interactions to their potential roles in defining infection outcomes, we will elucidate the functional contribution of candidate RNA binders to cell-state transitions occurring at the single-cell level.
This work will improve our understanding of viral infections at the molecular level and reveal novel antiviral mechanisms with potential for therapeutic exploration.

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