Small Molecular Inactivators of HIV

我们已经开发和研究了我们的分子，包括活性形式和前药。我们已经为这些分子开发了大规模的合成，并合作研究它们的抗病毒活性和评估它们的临床前毒性。总体而言，这些分子在人类外周血单核细胞中显示出广泛的HIV-1临床分离株活性，表现出与FDA批准的其他HIV药物协同抗病毒作用的添加剂，并且在14代后未能产生HIV耐药株。我们的分子没有明显的毒性。我们的分子也被成功地开发成作为杀菌剂应用的平台。我们目前正在研究这些分子的详细机制，进行体内研究，密切检查药物动力学和代谢，并探索这些分子是否具有抗其他病毒的活性。

We have developed and studied our molecule both in the active form and as a prodrug. We have developed large-scale syntheses for these molecules and worked in collaboration to study their antiviral activity and evaluate their preclinical toxicity. Overall, the molecules show broad range of activity across a panel of HIV-1 clinical isolates in human PBMCs, demonstrate additive to synergistic antiviral interactions with other FDA-approved HIV drugs, and fail to allow the generation of HIV resistant strains after 14 passages. There is no observable toxicity with our molecules. Our molecules have also been successfully developed into platforms for application as a microbicide. We are currently examining the detailed mechanism of these molecules, performing an in vivo study, closely examining the pharmacokinetics and metabolism, and exploring whether these molecules have antiviral activity against other viruses.