1350624-48-4Relevant articles and documents
Structure-Guided Design of Potent Inhibitors of SARS-CoV-2 3CL Protease: Structural, Biochemical, and Cell-Based Studies
Dampalla, Chamandi S.,Rathnayake, Athri D.,Perera, Krishani Dinali,Jesri, Abdul-Rahman M.,Nguyen, Harry Nhat,Miller, Matthew J.,Thurman, Hayden A.,Zheng, Jian,Kashipathy, Maithri M.,Battaile, Kevin P.,Lovell, Scott,Perlman, Stanley,Kim, Yunjeong,Groutas, William C.,Chang, Kyeong-Ok
, p. 17846 - 17865 (2021/12/13)
The COVID-19 pandemic is having a major impact on public health worldwide, and there is an urgent need for the creation of an armamentarium of effective therapeutics, including vaccines, biologics, and small-molecule therapeutics, to combat SARS-CoV-2 and emerging variants. Inspection of the virus life cycle reveals multiple viral- and host-based choke points that can be exploited to combat the virus. SARS-CoV-2 3C-like protease (3CLpro), an enzyme essential for viral replication, is an attractive target for therapeutic intervention, and the design of inhibitors of the protease may lead to the emergence of effective SARS-CoV-2-specific antivirals. We describe herein the results of our studies related to the application of X-ray crystallography, the Thorpe–Ingold effect, deuteration, and stereochemistry in the design of highly potent and nontoxic inhibitors of SARS-CoV-2 3CLpro.
MACROCYCLIC AND PEPTIDOMIMETIC COMPOUNDS AS BROAD-SPECTRUM ANTIVIRALS AGAINST 3C OR 3C-LIKE PROTEASES OF PICORNAVIRUSES, CALICIVIRUSES AND CORONAVIRUSES
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, (2013/11/19)
Antiviral protease inhibitors, including macrocylic transition state inhibitors and peptidomimetics are disclosed, along with related antiviral compounds, and methods of using the same to treat or prevent viral infection and disease. The compounds possess broad-spectrum activity against viruses that belong to the picornavirus-like supercluster, which include important human and animal pathogens including noroviruses, sapoviruses, enteroviruses, poliovirus, foot-and-mouth disease virus, hepatitis A virus, human rhinovirus (cause of common cold), human coronavirus (another cause of common cold), transmissible gastroenteritis virus, murine hepatitis virus, feline infectious peritonitis virus, and severe acute respiratory syndrome coronavirus.
Inhibition of norovirus 3CL protease by bisulfite adducts of transition state inhibitors
Mandadapu, Sivakoteswara Rao,Gunnam, Mallikarjuna Reddy,Tiew, Kok-Chuan,Uy, Roxanne Adeline Z.,Prior, Allan M.,Alliston, Kevin R.,Hua, Duy H.,Kim, Yunjeong,Chang, Kyeong-Ok,Groutas, William C.
, p. 62 - 65 (2013/02/23)
Noroviruses are the most common cause of acute viral gastroenteritis, accounting for >21 million cases annually in the US alone. Norovirus infections constitute an important health problem for which there are no specific antiviral therapeutics or vaccines. In this study, a series of bisulfite adducts derived from representative transition state inhibitors (dipeptidyl aldehydes and α-ketoamides) was synthesized and shown to exhibit anti-norovirus activity in a cell-based replicon system. The ED 50 of the most effective inhibitor was 60 nM. This study demonstrates for the first time the utilization of bisulfite adducts of transition state inhibitors in the inhibition of norovirus 3C-like protease in vitro and in a cell-based replicon system. The approach described herein can be extended to the synthesis of the bisulfite adducts of other classes of transition state inhibitors of serine and cysteine proteases, such as α-ketoheterocycles and α-ketoesters.
