Lattice engineering enables definition of molecular features allowing for potent small-molecule inhibition of HIV-1 entry
Temsavir, a compound that inhibits HIV entry by binding envelope (Env), is currently in clinical development. Here, Lai et al. identify a more than 10-fold improved compound and, using lattice engineering, obtain crystal structures that give insights into improved inhibition between small molecules...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2019-01-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-018-07851-1 |
| id |
doaj-8c1780f80cef41df909afde553e1a2ab |
|---|---|
| record_format |
Article |
| spelling |
doaj-8c1780f80cef41df909afde553e1a2ab2021-05-11T11:40:18ZengNature Publishing GroupNature Communications2041-17232019-01-0110111110.1038/s41467-018-07851-1Lattice engineering enables definition of molecular features allowing for potent small-molecule inhibition of HIV-1 entryYen-Ting Lai0Tao Wang1Sijy O’Dell2Mark K. Louder3Arne Schön4Crystal S. F. Cheung5Gwo-Yu Chuang6Aliaksandr Druz7Bob Lin8Krisha McKee9Dongjun Peng10Yongping Yang11Baoshan Zhang12Alon Herschhorn13Joseph Sodroski14Robert T. Bailer15Nicole A. Doria-Rose16John R. Mascola17David R. Langley18Peter D. Kwong19Vaccine Research Center, NIAID, National Institutes of HealthDepartments of Discovery Chemistry and Molecular Technologies, Bristol-Myers Squibb Research and DevelopmentVaccine Research Center, NIAID, National Institutes of HealthVaccine Research Center, NIAID, National Institutes of HealthDepartment of Biology, Johns Hopkins UniversityVaccine Research Center, NIAID, National Institutes of HealthVaccine Research Center, NIAID, National Institutes of HealthVaccine Research Center, NIAID, National Institutes of HealthVaccine Research Center, NIAID, National Institutes of HealthVaccine Research Center, NIAID, National Institutes of HealthVaccine Research Center, NIAID, National Institutes of HealthVaccine Research Center, NIAID, National Institutes of HealthVaccine Research Center, NIAID, National Institutes of HealthDepartment of Cancer Immunology and Virology, Dana–Farber Cancer Institute, Harvard Medical SchoolDepartment of Cancer Immunology and Virology, Dana–Farber Cancer Institute, Harvard Medical SchoolVaccine Research Center, NIAID, National Institutes of HealthVaccine Research Center, NIAID, National Institutes of HealthVaccine Research Center, NIAID, National Institutes of HealthComputer Assisted Drug Design, Bristol-Myers Squibb Research and DevelopmentVaccine Research Center, NIAID, National Institutes of HealthTemsavir, a compound that inhibits HIV entry by binding envelope (Env), is currently in clinical development. Here, Lai et al. identify a more than 10-fold improved compound and, using lattice engineering, obtain crystal structures that give insights into improved inhibition between small molecules and Env.https://doi.org/10.1038/s41467-018-07851-1 |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Yen-Ting Lai Tao Wang Sijy O’Dell Mark K. Louder Arne Schön Crystal S. F. Cheung Gwo-Yu Chuang Aliaksandr Druz Bob Lin Krisha McKee Dongjun Peng Yongping Yang Baoshan Zhang Alon Herschhorn Joseph Sodroski Robert T. Bailer Nicole A. Doria-Rose John R. Mascola David R. Langley Peter D. Kwong |
| spellingShingle |
Yen-Ting Lai Tao Wang Sijy O’Dell Mark K. Louder Arne Schön Crystal S. F. Cheung Gwo-Yu Chuang Aliaksandr Druz Bob Lin Krisha McKee Dongjun Peng Yongping Yang Baoshan Zhang Alon Herschhorn Joseph Sodroski Robert T. Bailer Nicole A. Doria-Rose John R. Mascola David R. Langley Peter D. Kwong Lattice engineering enables definition of molecular features allowing for potent small-molecule inhibition of HIV-1 entry Nature Communications |
| author_facet |
Yen-Ting Lai Tao Wang Sijy O’Dell Mark K. Louder Arne Schön Crystal S. F. Cheung Gwo-Yu Chuang Aliaksandr Druz Bob Lin Krisha McKee Dongjun Peng Yongping Yang Baoshan Zhang Alon Herschhorn Joseph Sodroski Robert T. Bailer Nicole A. Doria-Rose John R. Mascola David R. Langley Peter D. Kwong |
| author_sort |
Yen-Ting Lai |
| title |
Lattice engineering enables definition of molecular features allowing for potent small-molecule inhibition of HIV-1 entry |
| title_short |
Lattice engineering enables definition of molecular features allowing for potent small-molecule inhibition of HIV-1 entry |
| title_full |
Lattice engineering enables definition of molecular features allowing for potent small-molecule inhibition of HIV-1 entry |
| title_fullStr |
Lattice engineering enables definition of molecular features allowing for potent small-molecule inhibition of HIV-1 entry |
| title_full_unstemmed |
Lattice engineering enables definition of molecular features allowing for potent small-molecule inhibition of HIV-1 entry |
| title_sort |
lattice engineering enables definition of molecular features allowing for potent small-molecule inhibition of hiv-1 entry |
| publisher |
Nature Publishing Group |
| series |
Nature Communications |
| issn |
2041-1723 |
| publishDate |
2019-01-01 |
| description |
Temsavir, a compound that inhibits HIV entry by binding envelope (Env), is currently in clinical development. Here, Lai et al. identify a more than 10-fold improved compound and, using lattice engineering, obtain crystal structures that give insights into improved inhibition between small molecules and Env. |
| url |
https://doi.org/10.1038/s41467-018-07851-1 |
| work_keys_str_mv |
AT yentinglai latticeengineeringenablesdefinitionofmolecularfeaturesallowingforpotentsmallmoleculeinhibitionofhiv1entry AT taowang latticeengineeringenablesdefinitionofmolecularfeaturesallowingforpotentsmallmoleculeinhibitionofhiv1entry AT sijyodell latticeengineeringenablesdefinitionofmolecularfeaturesallowingforpotentsmallmoleculeinhibitionofhiv1entry AT markklouder latticeengineeringenablesdefinitionofmolecularfeaturesallowingforpotentsmallmoleculeinhibitionofhiv1entry AT arneschon latticeengineeringenablesdefinitionofmolecularfeaturesallowingforpotentsmallmoleculeinhibitionofhiv1entry AT crystalsfcheung latticeengineeringenablesdefinitionofmolecularfeaturesallowingforpotentsmallmoleculeinhibitionofhiv1entry AT gwoyuchuang latticeengineeringenablesdefinitionofmolecularfeaturesallowingforpotentsmallmoleculeinhibitionofhiv1entry AT aliaksandrdruz latticeengineeringenablesdefinitionofmolecularfeaturesallowingforpotentsmallmoleculeinhibitionofhiv1entry AT boblin latticeengineeringenablesdefinitionofmolecularfeaturesallowingforpotentsmallmoleculeinhibitionofhiv1entry AT krishamckee latticeengineeringenablesdefinitionofmolecularfeaturesallowingforpotentsmallmoleculeinhibitionofhiv1entry AT dongjunpeng latticeengineeringenablesdefinitionofmolecularfeaturesallowingforpotentsmallmoleculeinhibitionofhiv1entry AT yongpingyang latticeengineeringenablesdefinitionofmolecularfeaturesallowingforpotentsmallmoleculeinhibitionofhiv1entry AT baoshanzhang latticeengineeringenablesdefinitionofmolecularfeaturesallowingforpotentsmallmoleculeinhibitionofhiv1entry AT alonherschhorn latticeengineeringenablesdefinitionofmolecularfeaturesallowingforpotentsmallmoleculeinhibitionofhiv1entry AT josephsodroski latticeengineeringenablesdefinitionofmolecularfeaturesallowingforpotentsmallmoleculeinhibitionofhiv1entry AT roberttbailer latticeengineeringenablesdefinitionofmolecularfeaturesallowingforpotentsmallmoleculeinhibitionofhiv1entry AT nicoleadoriarose latticeengineeringenablesdefinitionofmolecularfeaturesallowingforpotentsmallmoleculeinhibitionofhiv1entry AT johnrmascola latticeengineeringenablesdefinitionofmolecularfeaturesallowingforpotentsmallmoleculeinhibitionofhiv1entry AT davidrlangley latticeengineeringenablesdefinitionofmolecularfeaturesallowingforpotentsmallmoleculeinhibitionofhiv1entry AT peterdkwong latticeengineeringenablesdefinitionofmolecularfeaturesallowingforpotentsmallmoleculeinhibitionofhiv1entry |
| _version_ |
1721446204620931072 |