HIV Drug Development

Structure showing different elements of a D-peptide inhibitor (PIE12, yellow) binding to its HIV target.

Our NIH P50 CHEETAH Center supports basic research in HIV structural biology and molecular virology, with the long-term goal of identifying effective new strategies for therapies, vaccines, and cures. Fundamental studies of HIV capsid structure and function performed by Sundquist, Hill, and colleagues formed the basis for Gilead’s development of highly potent, and remarkably long-lasting HIV capsid inhibitors that support quarterly dosing. These inhibitors have now entered Phase II clinical trials. Similarly, pioneering studies of D-peptide inhibitors by Kay and colleagues produced a highly potent inhibitor of HIV entry that will enter Phase I trials in 2020.


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Pharmacokinetic and chemical synthesis optimization of a potent D-peptide HIV entry inhibitor suitable for extended-release delivery. Redman JS, Francis JN, Marquardt R, Papac D, Mueller AL, Eckert DM, Welch BD, Kay MS. Molecular Pharmacology. 2018 Mar;15(3):1169.

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A highly potent long-acting small-molecule HIV-1 capsid inhibitor with efficacy in a humanized mouse model. Yant SR, Mulato A, Hansen D, Tse WC, Niedziela-Majka A, Zhang JR, Stepan GJ, Jin D, Wong MH, Perreira JM, Singer E, Papalia GA, Hu EY, Zheng J, Lu B, Schroeder SD, Chou K, Ahmadyar S, Liclican A, Yu H, Novikov N, Paoli E, Gonik D, Ram RR, Hung M, McDougall WM, Brass AL, Sundquist WI, Cihlar T, Link JO. Nature Medicine. 2019 Sep;25(9):1377.

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