TY - JOUR
T1 - Structural basis of HIV inhibition by L-nucleosides
T2 - Opportunities for drug development and repurposing
AU - Ruiz, Francesc X.
AU - Hoang, Anthony
AU - Dilmore, Christopher R.
AU - DeStefano, Jeffrey J.
AU - Arnold, Eddy
N1 - Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/7
Y1 - 2022/7
N2 - Infection with HIV can cripple the immune system and lead to AIDS. Hepatitis B virus (HBV) is a hepadnavirus that causes human liver diseases. Both pathogens are major public health problems affecting millions of people worldwide. The polymerases from both viruses are the most common drug target for viral inhibition, sharing common architecture at their active sites. The L-nucleoside drugs emtricitabine and lamivudine are widely used HIV reverse transcriptase (RT) and HBV polymerase (Pol) inhibitors. Nevertheless, structural details of their binding to RT(Pol)/nucleic acid remained unknown until recently. Here, we discuss the implications of these structures, alongside related complexes with L-dNTPs, for the development of novel L-nucleos(t)ide drugs, and prospects for repurposing them.
AB - Infection with HIV can cripple the immune system and lead to AIDS. Hepatitis B virus (HBV) is a hepadnavirus that causes human liver diseases. Both pathogens are major public health problems affecting millions of people worldwide. The polymerases from both viruses are the most common drug target for viral inhibition, sharing common architecture at their active sites. The L-nucleoside drugs emtricitabine and lamivudine are widely used HIV reverse transcriptase (RT) and HBV polymerase (Pol) inhibitors. Nevertheless, structural details of their binding to RT(Pol)/nucleic acid remained unknown until recently. Here, we discuss the implications of these structures, alongside related complexes with L-dNTPs, for the development of novel L-nucleos(t)ide drugs, and prospects for repurposing them.
KW - HIV-1 reverse transcriptase
KW - L-nucleoside
KW - drug development
KW - drug resistance
KW - hepatitis B virus polymerase
KW - repurposing
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U2 - 10.1016/j.drudis.2022.02.016
DO - 10.1016/j.drudis.2022.02.016
M3 - Review article
C2 - 35218925
AN - SCOPUS:85126054890
SN - 1359-6446
VL - 27
SP - 1832
EP - 1846
JO - Drug Discovery Today
JF - Drug Discovery Today
IS - 7
ER -