Anti-HIV-1 gp120 polyclonal antibody [HRP]

Objectives: Fostemsavir is the prodrug of the HIV-1 attachment inhibitor temsavir and is currently under clinical assessment in heavily treatment-experienced patients with limited therapeutic options. We evaluated the genotypic and phenotypic susceptibility to temsavir in a panel of samples collected from patients harbouring MDR strains enrolled in the Italian PRESTIGIO Registry. Methods: Plasma samples from 24 patients were used for HIV-1 gp120 sequencing, while viral tropism and susceptibility to temsavir were assessed through a homemade phenotypic assay with pseudotyped viruses expressing patient-derived Env protein. Results: Of the 24 patients enrolled, 18 (75%) were male, median (IQR) age was 55 years (52-61), time since HIV-1 diagnosis was 27 years (24-30), time on ART was 26 years (23-27) and 11 (46%) had a previous AIDS diagnosis. Exposure to entry inhibitors (maraviroc and/or enfuvirtide) had occurred in 19 (79%) patients. Among 23/24 gp120 sequences obtained, temsavir resistance-associated mutations (RAMs) were detected in three cases (two M426L and one S375N). Pseudotyped viruses were obtained from 23/24 samples and viral tropism was CXCR4-tropic, CCR5-tropic and dual/mixed-tropic in six, nine and eight cases, respectively. Phenotypic susceptibility to temsavir was comparable to the reference WT viruses NL4-3 and AD8 in all samples, irrespective of RAMs. Viral tropism and exposure to entry inhibitors did not impact temsavir susceptibility. Conclusions: These data support the use of fostemsavir as a valuable therapy option in patients harbouring MDR virus. The role of laboratory testing in optimal screening of patients eligible for fostemsavir treatment remains to be investigated.

Despite the significant progress in managing patients infected with HIV through the development of Highly Active Anti-Retroviral Therapy (HAART), major challenges and opportunities remain to be explored. Of particular interest, is the binding of glycopmtein 120 (gp120) to the primary cellular receptor Cluster of Differentiation 4 (CD4). In this work we describe our two phased computational process to identify useful compounds capable of binding to the gp120 protein for therapeutic purposes. We identified 187 compounds from the literature that conform to active binding sites on these proteins and use these as training/test sets. The data in the form of quantitative structure-activity relationships (QSAR) is downloaded from the ZINC database and transformed using principal components analysis. In the first phase we developed a Radial Basis Function neural network model that identifies potential inhibitors from a virtual screen of a subset of the ZINC database. In the second phase we modelled the top performing compounds using the Discovery Studio docking and screening software. By employing this approach, we identified that those compounds with a LogP value of appmx 2-4 performed well in the binding simulations while the lower scoring compounds do not bind well.