Abstract
A target-free and cell-based approach was applied to evaluate the anti-influenza properties of six newly synthesized benzoic acid derivatives. SA-2, the ethyl 4-(2-hydroxymethyl-5-oxopyrrolidin-1-yl)-3-[3-(3-methylbenzoyl)-thioureido] benzoate (compound 2) was screened as a potential drug candidate. In a cytopathic effect assay, SA-2 dose dependently inhibited H1N1, H3N2 and the oseltamivir-resistant mutant H1N1-H275Y influenza viruses in both virus-infected MDCK and A549 cells, with 50% effective concentrations (EC50) in MDCK cells of 9.6, 19.2 and 19.8 μM respectively, and 50% cytotoxic concentration (CC50) of 444.5 μM, showing competitive antiviral activity with oseltamivir in vitro. Orally administered SA-2 effectively protected mice infected with lethal doses of H1N1 or oseltamivir-resistant strain H1N1-H275Y, conferring 70% or 50% survival at a dosage of 100 mg/kg/d, reducing body weight loss, alleviating the influenza-induced acute lung injury, and reducing lung virus titer. Mechanistic studies showed that SA-2 efficiently inhibited the activity of RNA polymerase and suppressed NP and M1 levels during viral biosynthesis by interfering with gene transcription without having an obvious influence on virus entry and release....Continue Reading
References
Jul 8, 1999·Journal of Medicinal Chemistry·V R AtigaddaG W Laver
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jan 14, 2003·Nature Genetics·Akihide TakeuchiKen-ichi Isobe
Sep 3, 2004·Drugs·Alexander C Schmidt
Sep 30, 2005·The New England Journal of Medicine·Anne Moscona
Oct 12, 2005·Bioorganic & Medicinal Chemistry Letters·Chuanwen SunPei Zhou
May 6, 2008·Nature Structural & Molecular Biology·Delphine GuilligayStephen Cusack
May 12, 2009·Antiviral Research·Yousuke FurutaJohn D Morrey
Jan 8, 2010·Experimental & Molecular Medicine·Eun Ju JungBaik Lin Seong
Jun 15, 2010·Cell Host & Microbe·Tokiko WatanabeYoshihiro Kawaoka
Mar 29, 2011·Antiviral Research·Ilenia DeloguXavier de Lamballerie
May 20, 2011·BMC Infectious Diseases·Kristian ThorlundLehana Thabane
Jul 26, 2011·Antiviral Research·Lili ChenChanglin Zhou
Nov 8, 2011·Antiviral Research·Junjie ZhangXin Ye
Mar 23, 2012·Expert Opinion on Drug Discovery·Colm AtkinsJames W Noah
Jun 6, 2012·Bioorganic & Medicinal Chemistry Letters·James R BurgesonDongcheng Dai
Sep 12, 2012·Journal of Medicinal Chemistry·Kung-Cheng LiuChi-Huey Wong
Jan 1, 2013·Antiviral Research·Sook-Kwan LeangAeron C Hurt
Feb 23, 2013·Science·Jin-Hyo KimStephen G Withers
Apr 26, 2013·The New England Journal of Medicine·Qun LiZijian Feng
Apr 18, 2014·Journal of Immunology Research·Hongye FanYayi Hou
Apr 30, 2014·The Journal of Antimicrobial Chemotherapy·E Bart TarbetSimon P Tucker
May 27, 2014·Biochemical and Biophysical Research Communications·Yutaka SasakiYoko Aida
May 29, 2014·Current Opinion in Virology·Aeron C Hurt
Jun 22, 2014·The Journal of Infectious Diseases·Hui-Ling YenJoseph Sriyal Malik Peiris
Aug 1, 2014·Archives of Virology·Yue DingChanglin Zhou
Dec 31, 2014·Antimicrobial Agents and Chemotherapy·Randal A ByrnPaul S Charifson
Apr 3, 2015·Clinical and Vaccine Immunology : CVI·Wenling WangLi Ruan
Citations
Jun 9, 2016·Viruses·Ji-Hye LeeKyung Hyun Kim
Sep 28, 2016·Protein Engineering, Design & Selection : PEDS·Shangfei ZhangShunyi Zhu
Apr 21, 2018·Archives of Insect Biochemistry and Physiology·Jing ZhouHui Ai
Nov 1, 2016·Virus Genes·Hongren QuHongxuan He
Nov 10, 2018·Virology Journal·Guoyao MaHongxuan He
Dec 18, 2019·International Journal of Molecular Sciences·Min GuoChanglin Zhou
Oct 13, 2020·Virologica Sinica·Mengwei LiMin Guo
Mar 16, 2021·Virus Research·Li-Peng ShanJian-Ping Chen
May 1, 2021·Frontiers in Pharmacology·Yanni LaiGeng Li