Inhibition of HIV and virus replication by polysulphated... : AIDS (original) (raw)

Original paper: PDF Only

HOE/BAY 946, a new antiviral compound

Biesert, Lothar; Suhartono, Hary; Winkler, Irvin*; Meichsner, Christoph*; Helsberg, Matthias*; Hewlett, Guy†; Klimetzek, Volker†; Mölling, Karin‡; Schlumberger, Horst-Dieter†; Schrinner, Elmar*; Brede, Hans-Dieter; Rübsamen-Waigmann, Helga

From the Chemotherapeutisches Forschungsinstitut Georg-Speyer-Haus, Paul-Ehrlich-Str. 42, D-6000 Frankfurt 70, *Hoechst AG, D-6230 Frankfurt 80, †Bayer AG, D-5600 Wuppertal-Elberfeld and ‡ Max-Planck-Institut für Molekulare Genetik, Ihnestr. 73, D-1000 Berlin 33, Federal Republic of Germany.

Abstract

Xylanpoly-(hydrogen sulphate) disodium salt with a molecular weight of about 6000 daltons (HOE/BAY 946) completely inhibited syncytium formation induced by the infection of T lymphocytes with HIV as well as viral replication at concentrations above 25μg/ml. This dose was found to be inhibitory for several strains of HIV-1 and HIV-2. Low molecular weight fractions of the compound were less active against HIV, and high molecular derivatives were as active as HOE/BAY 946. A direct influence of the drug on the infectivity of the virus could not be demonstrated. The drug inhibited the reverse transcriptase of HIV. Treatment of permanently HIV-infected U937 cells resulted in a drastic reduction of virus particles released into the supernatant and points to an additional mode of action. A therapeutic effect of HOE/BAY 946 against retroviruses in vivo could be demonstrated in Friend leukaemia virus-infected mice. A clinical pilot study with the compound was started recently in Germany with AIDS patients who did not tolerate or refused to take zidovudine and with asymptomatic virus carriers.