1 / 5

Use of Bioisosteric Replacement Tools to Obtain Mutation-Resistant Antivirals

Mattia CF Prosperi University of “Roma TRE” Faculty of Computer Science Engineering Dept. of Computer Science and Automation (DIA) via della vasca navale, 79 -00146- Roma. Use of Bioisosteric Replacement Tools to Obtain Mutation-Resistant Antivirals. Outline.

sherry
Download Presentation

Use of Bioisosteric Replacement Tools to Obtain Mutation-Resistant Antivirals

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Mattia CF Prosperi University of “Roma TRE” Faculty of Computer Science Engineering Dept. of Computer Science and Automation (DIA) via della vasca navale, 79 -00146- Roma Use of Bioisosteric Replacement Tools to Obtain Mutation-Resistant Antivirals

  2. Outline • HIV-1 is a highly mutating virus which is able to develop quickly resistance to antiretrovirals • Combined treatments (HAART) are the current choice to lower the viral load to undetectable levels in the body • Even if the patients’ expected survival time is increased, HIV-1 ultimately can develop cross-resistance • HAARTs are harmful for the body due to toxicity

  3. Aim • Mutational pathways of HIV-1 can be explored with respect to natural evolution and under drug pressure • Phenotypic tests, naïve vs treated population samples • New compounds can be designed not only to be effective against wild type strains, but also against resistant population

  4. Integration of Techniques • Viral Resistance to commercial Drugs • Analyses on in-vitro phenotypic tests and Population sampling • Derivation of different mutational sets • Huge genomic data base • Los Alamos (more than 27,000 HIV-1 protease sequences) • Molecular Modelling and Computer Aided Drug Design • HIV-1 protease 3D structure modelling • Wild type sequences, Mutant sequences • MOL and Modeller • Molecular Interaction Fields • Scaffold Hopping • GRID, SHOP

  5. Results (preliminary) • Two mutant structures of HIV-1 protease were considered • These structures were exhibiting opposite phenotypic behaviour for two compounds (SQV and DRV) • SHOP was able to suggest in both cases the replacement of fragments from one drug to another when considering the mutant structures

More Related