Tim Krischuns
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View article: Visualizing influenza A virus assembly by in situ cryo-electron tomography
Visualizing influenza A virus assembly by in situ cryo-electron tomography Open
Influenza A virus (IAV) forms pleomorphic particles that package eight ribonucleoprotein complexes (vRNPs), each carrying a distinct RNA genome segment. vRNPs assemble in the nucleus and undergo selective sorting during Rab11a-mediated tra…
View article: Noncovalent Inhibitors of SARS-CoV-2 Main Protease: A Rescaffolding Attempt
Noncovalent Inhibitors of SARS-CoV-2 Main Protease: A Rescaffolding Attempt Open
Out of the results of the sole large-scale screening for inhibitors of SARS-CoV-1 main protease reported in 2013, attempts to improve the identified 3-pyridyl-bearing hits have been conducted in research laboratories, either on this enzyme…
View article: Mechanism of Co-Transcriptional Cap-Snatching by Influenza Polymerase
Mechanism of Co-Transcriptional Cap-Snatching by Influenza Polymerase Open
Influenza virus mRNA is stable and competent for nuclear export and translation because it receives a 5′ cap(1) structure in a process called cap-snatching 1 . During cap-snatching, the viral RNA-dependent RNA polymerase (FluPol) binds to …
View article: The RBPome of influenza A virus NP-mRNA reveals a role for TDP-43 in viral replication
The RBPome of influenza A virus NP-mRNA reveals a role for TDP-43 in viral replication Open
Genome-wide approaches have significantly advanced our knowledge of the repertoire of RNA-binding proteins (RBPs) that associate with cellular polyadenylated mRNAs within eukaryotic cells. Recent studies focusing on the RBP interactomes of…
View article: Structures of influenza A and B replication complexes explain avian to human host adaption and reveal a role of ANP32 as an electrostatic chaperone for the apo-polymerase
Structures of influenza A and B replication complexes explain avian to human host adaption and reveal a role of ANP32 as an electrostatic chaperone for the apo-polymerase Open
Replication of influenza viral RNA depends on at least two viral polymerases, a parental replicase and an encapsidase, and cellular factor ANP32. ANP32 comprises an LRR domain and a long C-terminal low complexity acidic region (LCAR). Here…
View article: High-resolution structure of a replication-initiation like configuration of influenza polymerase active site visualises the essential role of a conserved dibasic motif in the PA subunit
High-resolution structure of a replication-initiation like configuration of influenza polymerase active site visualises the essential role of a conserved dibasic motif in the PA subunit Open
Influenza polymerase, comprising subunits PA, PB1 and PB2, transcribes the negative-sense genomic viral RNA (vRNA) into mRNA or replicates it first into complementary RNA (cRNA) and then back to vRNA. Here we investigate the mechanism of d…
View article: Multivalent Dynamic Colocalization of Avian Influenza Polymerase and Nucleoprotein by Intrinsically Disordered ANP32A Reveals the Molecular Basis of Human Adaptation
Multivalent Dynamic Colocalization of Avian Influenza Polymerase and Nucleoprotein by Intrinsically Disordered ANP32A Reveals the Molecular Basis of Human Adaptation Open
Adaptation of avian influenza RNA polymerase (FluPol) to human cells requires mutations on the 627-NLS domains of the PB2 subunit. The E627K adaptive mutation compensates a 33-amino-acid deletion in the acidic intrinsically disordered doma…
View article: The host RNA polymerase II C-terminal domain is the anchor for replication of the influenza virus genome
The host RNA polymerase II C-terminal domain is the anchor for replication of the influenza virus genome Open
Summary The current model is that the influenza virus polymerase (FluPol) binds either to host RNA polymerase II (RNAP II) or to the acidic nuclear phosphoprotein 32 (ANP32), which drives its conformation and activity towards transcription…
View article: Multivalent dynamic colocalization of avian influenza polymerase and nucleoprotein by intrinsically disordered ANP32A reveals the molecular basis of human adaptation
Multivalent dynamic colocalization of avian influenza polymerase and nucleoprotein by intrinsically disordered ANP32A reveals the molecular basis of human adaptation Open
Adaptation of avian influenza RNA polymerase (FluPol) to human cells requires mutations on the 627-NLS domains of the PB2 subunit. The E627K adaptive mutation compensates a 33-amino-acid deletion in the acidic intrinsically disordered doma…
View article: The RBPome of influenza A virus mRNA reveals a role for TDP-43 in viral replication
The RBPome of influenza A virus mRNA reveals a role for TDP-43 in viral replication Open
Recent technical advances have significantly improved our understanding of the RNA-binding protein (RBP) repertoire present within eukaryotic cells, with a particular focus on the RBPs that interact with cellular polyadenylated mRNAs. Howe…
View article: Correction: Type B and type A influenza polymerases have evolved distinct binding interfaces to recruit the RNA polymerase II CTD
Correction: Type B and type A influenza polymerases have evolved distinct binding interfaces to recruit the RNA polymerase II CTD Open
[This corrects the article DOI: 10.1371/journal.ppat.1010328.].
View article: Design and synthesis of naturally-inspired SARS-CoV-2 inhibitors
Design and synthesis of naturally-inspired SARS-CoV-2 inhibitors Open
A naturally inspired chemical library of 25 molecules was synthesised guided by 3-D dimensionality and natural product likeness proved to have antiviral activity against SARS-CoV-2.
View article: Type B and type A influenza polymerases have evolved distinct binding interfaces to recruit the RNA polymerase II CTD
Type B and type A influenza polymerases have evolved distinct binding interfaces to recruit the RNA polymerase II CTD Open
During annual influenza epidemics, influenza B viruses (IBVs) co-circulate with influenza A viruses (IAVs), can become predominant and cause severe morbidity and mortality. Phylogenetic analyses suggest that IAVs (primarily avian viruses) …
View article: Type B and Type A influenza polymerases have evolved distinct binding interfaces to recruit the RNA polymerase II CTD
Type B and Type A influenza polymerases have evolved distinct binding interfaces to recruit the RNA polymerase II CTD Open
During annual influenza epidemics, influenza B viruses (IBVs) co-circulate with influenza A viruses (IAVs), can become predominant and cause severe morbidity and mortality. Phylogenetic analyses suggest that IAVs (primarily avian viruses) …
View article: The ubiquitination landscape of the Influenza A Virus polymerase
The ubiquitination landscape of the Influenza A Virus polymerase Open
During influenza A virus (IAV) infections, viral proteins are targeted by cellular E3 ligases for modification with ubiquitin. Here, we decipher and functionally explore the ubiquitination landscape of the IAV polymerase during infection o…
View article: A highly sensitive cell-based luciferase assay for high-throughput automated screening of SARS-CoV-2 nsp5/3CLpro inhibitors
A highly sensitive cell-based luciferase assay for high-throughput automated screening of SARS-CoV-2 nsp5/3CLpro inhibitors Open
Effective drugs against SARS-CoV-2 are urgently needed to treat severe cases of infection and for prophylactic use. The main viral protease (nsp5 or 3CLpro) represents an attractive and possibly broad-spectrum target for drug development a…
View article: Dissecting the mechanism of signaling-triggered nuclear export of newly synthesized influenza virus ribonucleoprotein complexes
Dissecting the mechanism of signaling-triggered nuclear export of newly synthesized influenza virus ribonucleoprotein complexes Open
Significance Influenza viruses (IV) replicate in the nucleus. Export of newly produced genomes, packaged in viral ribonucleoprotein (vRNP) complexes, relies on the nuclear CRM1 export pathway and appears to be timely controlled by virus-in…
View article: Phosphorylation of TRIM28 Enhances the Expression of IFN-β and Proinflammatory Cytokines During HPAIV Infection of Human Lung Epithelial Cells
Phosphorylation of TRIM28 Enhances the Expression of IFN-β and Proinflammatory Cytokines During HPAIV Infection of Human Lung Epithelial Cells Open
Human infection with highly pathogenic avian influenza viruses (HPAIV) is often associated with severe tissue damage due to hyperinduction of interferons and proinflammatory cytokines. The reasons for this excessive cytokine expression are…