• Publications
  • Influence
Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors
TLDR
The pharmacokinetic characterization of the optimized inhibitor reveals a pronounced lung tropism and suitability for administration by the inhalative route and work that may provide a basis for development of anticoronaviral drugs. Expand
Coronavirus Main Proteinase (3CLpro) Structure: Basis for Design of Anti-SARS Drugs
TLDR
Molecular modeling suggests that available rhinovirus 3Cpro inhibitors may be modified to make them useful for treating SARS, and a homology model for SARS coronavirus (SARS-CoV) Mpro is constructed. Expand
The crystal structures of severe acute respiratory syndrome virus main protease and its complex with an inhibitor
TLDR
This series of crystal structures, which is the first, to the authors' knowledge, of any protein from the SARS virus, reveal substantial pH-dependent conformational changes, and an unexpected mode of inhibitor binding, providing a structural basis for rational drug design. Expand
Conformational Antagonism between Opposing Active Sites in a Bifunctional RelA/SpoT Homolog Modulates (p)ppGpp Metabolism during the Stringent Response
TLDR
Reciprocal regulation of the antagonistic catalytic activities, suggested by the structure, is supported by mutagenesis experiments and appears to involve ligand-induced signal transmission between the two active sites. Expand
Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra α-helical domain
TLDR
The crystal structure of the 33.1 kDa transmissible gastroenteritis (corona)virus Mpro is reported and illustrates that RNA viruses have evolved unprecedented variations of the classical chymotrypsin fold. Expand
Crystal structure of active elongation factor Tu reveals major domain rearrangements
TLDR
Comparison of the structure with that of EF-Tu–GDP reveals major mutual rearrange-ments of the three domains of the molecule, and molecular mechanisms are proposed for transductlon and amplification of the signal induced by GTP binding. Expand
Crystal structure of Zika virus NS2B-NS3 protease in complex with a boronate inhibitor
TLDR
The unusual dimer of the ZIKV protease:inhibitor complex seen in the crystal may provide a model for assemblies formed at high local concentrations of protease at the endoplasmatic reticulum membrane, the site of polyprotein processing. Expand
From SARS to MERS: crystallographic studies on coronaviral proteases enable antiviral drug design
TLDR
The crystal structure of the free SARS coronavirus Mpro and its dependence on pH is discussed, as are efforts to design inhibitors on the basis of these structures, and the role of X‐ray crystallography in structure‐assisted drug discovery against these targets is discussed. Expand
Structure and functionality in flavivirus NS-proteins: Perspectives for drug design
TLDR
Structural and functional aspects emerging from the characterization of two main components (NS3 and NS5 proteins) of the flavivirus replication complex are reviewed to shed light on the design and development of antiviral drug leads. Expand
The SARS-Coronavirus-Host Interactome: Identification of Cyclophilins as Target for Pan-Coronavirus Inhibitors
TLDR
Overexpression of NSP1 and infection with live SARS-CoV strongly increased signalling through the Calcineurin/NFAT pathway and enhanced the induction of interleukin 2, compatible with late-stage immunopathogenicity and long-term cytokine dysregulation as observed in severe SARS cases. Expand
...
1
2
3
4
5
...