Universitè Laval

Arezki Azzi

Sheng-Xiang Lin

Guy Boivin

Caroline Gilbert

Alexandra Lambert

Michel J Tremblay

Melanie Martin

The invention is concerned with compounds, pharmaceutical compositions, screening methods, and therapeutic methods for preventing or reducing a human immunodeficiency virus type-1 (HIV-1) infection and/or propagation associated with dendritic cell immunoreceptor (DCIR). Described herein are compounds which bind on at least one three-dimensional cavity of the DCIR, the cavity(ies) being involved in the interaction between HIV-1 and DCIR. Also described are screening methods for identifying active inhibitors and method of using such inhibitors for the prevention or treatment of virus infections, and more particularly for reducing human immunodeficiency virus type-1 (HIV-1) binding, entry and/or replication in human cells.

Three-dimensional cavities of dendritic cell immunoreceptor (DCIR), compounds binding thereto and therapeutic applications related to inhibition of human immunodeficiency virus type-1 (HIV-1)

3D protein modeling and virtual screening of commercially-available compounds were performed to identify new inhibitors of the herpesvirus DNA polymerase, a key enzyme in the viral replication cycle. Two compounds (Nos 2 and 9) were particularly active against HSV-1 and HSV-2 strains and one compound (No 3) inhibited specifically cytomegalovirus (CMV) strains (overall hit rate of 25%). Some of the tested compounds inhibited wild-type viruses and strains resistant to current antiviral agents. New chemical entity derivatives of compound 2 with binding potential to the DNA polymerase retained an excellent activity against HSV-1, HSV-2 and VZV like the parental compound, as well against strains resistant to current antiviral agents. These non-nucleosidic herpesvirus DNA polymerase inhibitors with in vitro activity against drug-resistant clinical isolates warrant further pre-clinical studies.

Compounds for the inhibition of herpes viruses

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Riyadh, Saudi Arabia

Arezki Azzi