Structure-guided design, synthesis and evaluation of oxazolidinone-based inhibitors of norovirus 3CL protease
Damalanka, Vishnu C. Kim, Yunjeong Kankanamalage, Anushka C. Galasiti Rathnayake, Athri D. Mehzabeen, Nurjahan Battaile, Kevin P. Lovell, Scott Nguyen, Harry Nhat Lushington, Gerald H. Chang, Kyeong-Ok
Damalanka, Vishnu C.
Kim, Yunjeong
Kankanamalage, Anushka C. Galasiti
Rathnayake, Athri D.
Mehzabeen, Nurjahan
Battaile, Kevin P.
Lovell, Scott
Nguyen, Harry Nhat
Lushington, Gerald H.
Chang, Kyeong-Ok
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2018-01-01
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Transition-state inhibitors,Data quality,Macromolecular crystallography,Macrocyclic inhibitors,Substrate-specificity,Norwalk-virus,Discovery,Therapeutics,Receptor,Targets
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Citation
Damalanka, Vishnu C.; Kim, Yunjeong; Kankanamalage, Anushka C. Galasiti; Rathnayake, Athri D.; Mehzabeen, Nurjahan; Battaile, Kevin P.; Lovell, Scott; Nguyen, Harry Nhat; Lushington, Gerald H.; Chang, Kyeong-Ok; Groutas, William C. 2018. Structure-guided design, synthesis and evaluation of oxazolidinone-based inhibitors of norovirus 3CL protease. European Journal of Medicinal Chemistry, vol. 143:pp 881-890
Abstract
Acute nonbacterial gastroenteritis caused by noroviruses constitutes a global public health concern and a significant economic burden. There are currently no small molecule therapeutics or vaccines for the treatment of norovirus infections. A structure-guided approach was utilized in the design of a series of inhibitors of norovirus 3CL protease that embody an oxazolidinone ring as a novel design element for attaining optimal binding interactions. Low micromolar cell-permeable inhibitors that display ant-inorovirus activity have been identified. The mechanism of action, mode of binding, and structural rearrangements associated with the interaction of the inhibitors and the enzyme were elucidated using X-ray crystallography.
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Elsevier
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European Journal of Medicinal Chemistry;v.143
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0223-5234