1416992-27-2Relevant articles and documents
Structure-guided design and optimization of dipeptidyl inhibitors of norovirus 3CL protease. Structure-activity relationships and biochemical, X-ray crystallographic, cell-based, and in vivo studies
Galasiti Kankanamalage, Anushka C.,Kim, Yunjeong,Weerawarna, Pathum M.,Uy, Roxanne Adeline Z.,Damalanka, Vishnu C.,Mandadapu, Sivakoteswara Rao,Alliston, Kevin R.,Mehzabeen, Nurjahan,Battaile, Kevin P.,Lovell, Scott,Chang, Kyeong-Ok,Groutas, William C.
, p. 3144 - 3155 (2015/04/27)
Norovirus infection constitutes the primary cause of acute viral gastroenteritis. There are currently no vaccines or norovirus-specific antiviral therapeutics available for the management of norovirus infection. Norovirus 3C-like protease is essential for viral replication, consequently, inhibition of this enzyme is a fruitful avenue of investigation that may lead to the emergence of antinorovirus therapeutics. We describe herein the optimization of dipeptidyl inhibitors of norovirus 3C-like protease using iterative SAR, X-ray crystallographic, and enzyme and cell-based studies. We also demonstrate herein in vivo efficacy of an inhibitor using the murine model of norovirus infection.
Potent inhibition of norovirus by dipeptidyl α-hydroxyphosphonate transition state mimics
Mandadapu, Sivakoteswara Rao,Gunnam, Mallikarjuna Reddy,Galasiti Kankanamalage, Anushka C.,Uy, Roxanne Adeline Z.,Alliston, Kevin R.,Lushington, Gerald H.,Kim, Yunjeong,Chang, Kyeong-Ok,Groutas, William C.
, p. 5941 - 5944 (2013/10/22)
The design, synthesis, and evaluation of a series of dipeptidyl α-hydroxyphosphonates is reported. The synthesized compounds displayed high anti-norovirus activity in a cell-based replicon system, as well as high enzyme selectivity.
