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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.
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This article is published in Antiviral Research.The article was published on 2010-08-01 and is currently open access. It has received 296 citations till now. The article focuses on the topics: Flavivirus Infections & European union.

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Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: new prospects for an old drug

TL;DR: Ivermectin, a broadly used anti-helminthic drug, proved to be a highly potent inhibitor of YFV replication and inhibited, although less efficiently, the replication of several other flaviviruses, i.e. dengue fever, Japanese encephalitis and tick-borne encephalopathy viruses.
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In vitro reconstitution of SARS-coronavirus mRNA cap methylation

TL;DR: It is shown that mRNA cap methylation requires a third viral protein, nsp10, which acts as an essential trigger to complete RNA cap-1 formation, and sensitive in vitro inhibition assays of both activities show that aurintricarboxylic acid, active in SARS-CoV infected cells, targets both MTases with IC50 values in the micromolar range, providing a validated basis for anti-coronavirus drug design.
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Ten years of dengue drug discovery: Progress and prospects

TL;DR: The knowledge accumulated during the past decade has provided a better rationale for ongoing dengue drug discovery and it is optimistic that this continuous, concerted effort will lead to an effective d Dengue therapy.
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Crystal Structure and Functional Analysis of the SARS-Coronavirus RNA Cap 2′-O-Methyltransferase nsp10/nsp16 Complex

TL;DR: Two other crystal structures are presented, the inhibitor Sinefungin bound in the S-adenosylmethionine binding pocket and the tighter complex nsp10(Y96F)/nsp16, providing the first structural insight into the regulation of RNA capping enzymes in (+)RNA viruses.
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The flavivirus NS2B-NS3 protease-helicase as a target for antiviral drug development.

TL;DR: The NS2B-NS3 protein is associated with the endoplasmic reticulum membrane via its close interaction with the central hydrophilic region of the integral membrane protein this article.
References
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Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold.

TL;DR: Related sequences in both alpha and beta and in other enzymes that bind ATP or ADP in catalysis help to identify regions contributing to an adenine nucleotide binding fold in both ATP synthase subunits.
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Identification of four conserved motifs among the RNA-dependent polymerase encoding elements.

TL;DR: At the evolutionary level, the sequence similarities, gap distribution and distances between each motif strongly suggest that the ancestral polymerase module was encoded by an individual genetic element which was most closely related to the plus‐strand RNA viruses and the non‐viral retroposons.
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Phylogeny of the genus Flavivirus.

TL;DR: The phylogenetic study revealed for the first time that from the putative ancestor two branches, non-vector and vector-borne virus clusters, evolved and from the latter cluster emerged tick-borne and mosquito-borne viruses clusters.
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Two related superfamilies of putative helicases involved in replication, recombination, repair and expression of DNA and RNA genomes

TL;DR: A degree of similarity was revealed between the consensus pattern of conserved amino acid residues derived for the new superfamily and that of another recently described protein superfamily including a different set of prokaryotic, eukaryotic and viral (putative) helicases.
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