Non-active binders might restore back anti-retroviral drugs activity in resistant form of HIV protease

GOROSTEGUI, RENZO NAHUEL; FORLI, STEFANO; VISCONTI, DANA MARLENE; ANGELINA, EMILIO LUIS; PERUCHENA, NELIDA MARÍA; LUCHI, ADRIANO MARTÍN; BOGADO, MARÍA LUCRECIA; OLSON, ARTHUR

Montevideo

Congreso; XLII Congress of theoretical Chemists of Latin Expression; 2016

p { margin-bottom: 0.25cm; direction: ltr; line-height: 120%; text-align: left; }p.western { In this work we have performed long Molecular Dynamics (MD)simulations of wild type (WT) and 6X variant of HIV-PR bound to TL-3.The simulations show that on going from WT to 6X the equilibriumshift from closed to semi-open conformation of the flaps. Then weattached an small fragment Br6 to the flap of 6X and performed MDsimulations of the ternary complex 6X/TL-3/Br6 (see Fig1). To oursurprise, Br6 was able to restore back the enzyme to closedconformation of the flaps, that is to say it behaves much like the WTform of HIV-PR. This finding supports the hypothesis already proposedby Olson´s group that allosteric inhibitors, in combination withactive site inhibitors would likely increase the number of HIV-PRmutations required for significant clinical resistance to the highlyactive anti-retroviral therapy (HAART) ´cock- tails´.