[Pandemic relief volunteers-increasing resilience for disasters]. / Pandemienotfallhelfer ­ gestärkte Resilienz für den Katastrophenfall.

BACKGROUND: The corona pandemic demands new solutions from our health care system in order to expand treatment capacities in a resilient manner within a short period of time. The last stage of expansion is disaster protection, the resilience of which can also be improved by volunteers. However, these spontaneous volunteers require training in order to be integrated into the disaster relief structures. METHODS: In a step-by-step process, an ad hoc expert panel developed a curriculum for pandemic relief volunteer (PRV) training. RESULTS: The goal of PRV is to assist fully trained responders during transport and care in a makeshift hospital. The curriculum for training as a PRV comprises 16 instructional units of 45 min each on the topics of deployment, self-protection, protection of others, and direct patient care. The focus is on practical skills for which the participants can take responsibility for execution. CONCLUSION: The concept of the PRV is the first structured training and integration of spontaneous responders in German civil protection. It is not a substitute for fully trained full-time and voluntary staff, but can provide useful support.

Cis-mediated interactions of the SARS-CoV-2 frameshift RNA alter its conformations and affect function.

The RNA genome of SARS-CoV-2 contains a frameshift stimulatory element (FSE) that allows access to an alternative reading frame through -1 programmed ribosomal frameshifting (PRF). -1PRF in the 1a/1b gene is essential for efficient viral replication and transcription of the viral genome. -1PRF efficiency relies on the presence of conserved RNA elements within the FSE. One of these elements is a three-stemmed pseudoknot, although alternative folds of the frameshift site might have functional roles as well. Here, by complementing ensemble and single-molecule structural analysis of SARS-CoV-2 frameshift RNA variants with functional data, we reveal a conformational interplay of the 5' and 3' immediate regions with the FSE and show that the extended FSE exists in multiple conformations. Furthermore, limiting the base pairing of the FSE with neighboring nucleotides can favor or impair the formation of the alternative folds, including the pseudoknot. Our results demonstrate that co-existing RNA structures can function together to fine-tune SARS-CoV-2 gene expression, which will aid efforts to design specific inhibitors of viral frameshifting.

Pandemienotfallhelfer – gestärkte Resilienz für den Katastrophenfall Pandemic relief volunteers—increasing resilience for disasters

Hintergrund Die Coronapandemie fordert von unserem Gesundheitssystem neue Lösungen, um in kurzer Zeit die Behandlungskapazitäten belastbar zu erweitern. Als letzte Erweiterungsstufe dient der Katastrophenschutz, dessen Durchhaltefähigkeit auch durch freiwillige Personen verbessert werden kann. Diese Spontanhelfer benötigen jedoch eine Ausbildung, um in die Hilfeleistungsstrukturen eingebunden zu werden. Methode Ein Expertengremium mit langjähriger Erfahrung in der Entwicklung und Durchführung von Ausbildungen entwickelte in einem stufenweisen Prozess ein Curriculum zur Ausbildung des Pandemienotfallhelfers (PNH). Ergebnisse Der PNH soll die vollausgebildeten Helfer während des Transports und der Versorgung in einem Behelfskrankenhaus unterstützen. Das Curriculum zur Ausbildung zum PNH umfasst 16 Unterrichtseinheiten zu je 45 min zu den Themen Einsatz, Eigen- und Fremdschutz sowie unmittelbare Patientenversorgung. Im Fokus stehen praktische Fertigkeiten, für die die Teilnehmer die Durchführungsverantwortung übernehmen können. Schlussfolgerung Mit dem Konzept des PNH steht erstmalig eine strukturierte Vorbereitung und Eingliederung von Spontanhelfern im deutschen Katastrophenschutz zu Verfügung. Er ist kein Ersatz für vollausgebildete haupt- und ehrenamtliche Kräfte, sondern kann eine sinnvolle Unterstützung darstellen.

The short isoform of the host antiviral protein ZAP acts as an inhibitor of SARS-CoV-2 programmed ribosomal frameshifting.

Programmed ribosomal frameshifting (PRF) is a fundamental gene expression event in many viruses, including SARS-CoV-2. It allows production of essential viral, structural and replicative enzymes that are encoded in an alternative reading frame. Despite the importance of PRF for the viral life cycle, it is still largely unknown how and to what extent cellular factors alter mechanical properties of frameshift elements and thereby impact virulence. This prompted us to comprehensively dissect the interplay between the SARS-CoV-2 frameshift element and the host proteome. We reveal that the short isoform of the zinc-finger antiviral protein (ZAP-S) is a direct regulator of PRF in SARS-CoV-2 infected cells. ZAP-S overexpression strongly impairs frameshifting and inhibits viral replication. Using in vitro ensemble and single-molecule techniques, we further demonstrate that ZAP-S directly interacts with the SARS-CoV-2 RNA and interferes with the folding of the frameshift RNA element. Together, these data identify ZAP-S as a host-encoded inhibitor of SARS-CoV-2 frameshifting and expand our understanding of RNA-based gene regulation.

The SARS-CoV-2 RNA-protein interactome in infected human cells.

Characterizing the interactions that SARS-CoV-2 viral RNAs make with host cell proteins during infection can improve our understanding of viral RNA functions and the host innate immune response. Using RNA antisense purification and mass spectrometry, we identified up to 104 human proteins that directly and specifically bind to SARS-CoV-2 RNAs in infected human cells. We integrated the SARS-CoV-2 RNA interactome with changes in proteome abundance induced by viral infection and linked interactome proteins to cellular pathways relevant to SARS-CoV-2 infections. We demonstrated by genetic perturbation that cellular nucleic acid-binding protein (CNBP) and La-related protein 1 (LARP1), two of the most strongly enriched viral RNA binders, restrict SARS-CoV-2 replication in infected cells and provide a global map of their direct RNA contact sites. Pharmacological inhibition of three other RNA interactome members, PPIA, ATP1A1, and the ARP2/3 complex, reduced viral replication in two human cell lines. The identification of host dependency factors and defence strategies as presented in this work will improve the design of targeted therapeutics against SARS-CoV-2.