we show that LEDGINs are potent inhibitors of raltegravir resistant virus strains and vice versa: raltegravir retains full activity against LEDGIN resistant strains. While this report was under review, two independent reports confirming the mechanism of inhibition Oprozomib ic50 of integration were published. The inhibition of LEDGINs seems to also affect the contamination of progeny virus. The observation that LEDGINs not merely stop the integration of the incoming viral particle but in addition impair the infectivity of newly produced viral particles when present during production underlines the promise of LEDGINs for further scientific development. LEDGINs may both act on the multimerization state of integrase in the Pol protein or in the mature viral particle and for that reason modulate the catalytic action of integrase throughout the illness of a host cell. As an alternative, LEDGF/p75 might be required for correct virus assembly, and this function might be blocked by LEDGINs, making the viral particle less contagious. Apparently, in a recent report we described little peptides binding to LEDGF/p75 which Posttranslational modification (PTM) also induce a decrease of infectivity of the viral particles when developed in the presence of the peptides, suggesting a role for LEDGF/p75 in the construction of the viral particle. The step by step analysis of the underlying process of this effect will demand intensive investigation but possibly explains the steep slopes of the dose response curves of LEDGINs. In our antiviral profiling studies, LEDGINs proved active against a wide range of viral clades predominant in the populations on most places on the planet. By analogy to combinations of nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors, which were shown to be very effective in reducing the viral load in HIV-INFECTED individuals, LEDGINs and raltegravir might be merged in future therapy. Combination tests pifithrin alpha of LEDGINs and raltegravir claim that these inhibitors could act additively if not synergistically without proof antagonism despite sharing the same viral target. We present LEDGINs, small molecules that interact with the LEDGF/p75 binding pocket in integrase, being a promising new drug class in pre-clinical development for the treatment of HIV infected individuals. This new class of materials attacks viral integration by suppressing conversation with the mobile cofactor LEDGF/p75, required for integration into the HIV favorite sites, with a multiple edged mechanism of action, and by modulating the integrase quaternary construction, they inhibit catalytic activity and virus infectivity.