File:Simeprevir bound to HCV NS3 4A serine protease. (13329148744).jpg

Original file(900 × 956 pixels, file size: 378 KB, MIME type: image/jpeg)

Captions

Captions

Add a one-line explanation of what this file represents

Summary

edit
Description

Feel free to use this image, just link to <a href="http://www.enzymlogic.com" rel="noreferrer nofollow">www.enzymlogic.com</a>. Work done with the molecular visualization VMD program developed at the University of Illinois: <a href="http://www.ks.uiuc.edu/Research/vmd/" rel="noreferrer nofollow">www.ks.uiuc.edu/Research/vmd/</a>

Simeprevir is a second-generation NS3/4A serine protease inhibitor approved in November 2013 for the oral treatment of adults with genotype 1 and/or genotype 4 chronic hepatitis C (HCV). Simeprevir promotes rapid viral load reductions in chronic HCV patients and has a higher genetic barrier to resistance and better pharmacokinetic properties than first-generation antiviral drugs telaprevir and boceprevir. All of them are peptidomimetic transition state analogs (ball-and-stick model) of the natural substrate of NS3 protease (VDW model).

The main differences between them is their structural features and their interaction mechanism. Telaprevir and boceprevir are linear compounds while simeprevir is a macrocyclic compound. The striking advantages of simeprevir over the first-generation compounds seem to be promoted by a two-step binding mechanism. After the initial binding between simeprevir and NS3 protease, the complex isomerizes to a highly stable complex from which simeprevir dissociates very slowly (3.8 × 10−5 s−1 and a half-life of 5 h). The true biochemical potency is very low, approximately 60 pM.

References:

1.Simeprevir: first global approval. Vaidya A, Perry CM. Drugs. 2013 Dec;73(18):2093-106.

2.Inhibition and Binding Kinetics of the Hepatitis C Virus NS3 Protease Inhibitor ITMN-191 Reveals Tight Binding and Slow Dissociative Behavior. Rajagopalan Ravi et al. Biochemistry, 2009, 48 (11), pp 2559–2568
Date
Source Simeprevir bound to HCV NS3/4A serine protease.
Author Enzymlogic

Licensing

edit
w:en:Creative Commons
attribution share alike
This file is licensed under the Creative Commons Attribution-Share Alike 2.0 Generic license.
You are free:
  • to share – to copy, distribute and transmit the work
  • to remix – to adapt the work
Under the following conditions:
  • attribution – You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
  • share alike – If you remix, transform, or build upon the material, you must distribute your contributions under the same or compatible license as the original.
This image was originally posted to Flickr by Enzymlogic at https://flickr.com/photos/101755654@N08/13329148744 (archive). It was reviewed on 4 December 2018 by FlickreviewR 2 and was confirmed to be licensed under the terms of the cc-by-sa-2.0.

4 December 2018

File history

Click on a date/time to view the file as it appeared at that time.

Date/TimeThumbnailDimensionsUserComment
current14:42, 4 December 2018Thumbnail for version as of 14:42, 4 December 2018900 × 956 (378 KB)Luisbrudna (talk | contribs)Transferred from Flickr via #flickr2commons

There are no pages that use this file.