Antiviral activity of SA-2 against influenza A virus in vitro/vivo and its inhibition of RNA polymerase

Antiviral Research
Jie YuChanglin Zhou

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
Sep 30, 2005·The New England Journal of Medicine·Anne Moscona
May 6, 2008·Nature Structural & Molecular Biology·Delphine GuilligayStephen Cusack
Jan 8, 2010·Experimental & Molecular Medicine·Eun Ju JungBaik Lin Seong
Jun 15, 2010·Cell Host & Microbe·Tokiko WatanabeYoshihiro Kawaoka
May 20, 2011·BMC Infectious Diseases·Kristian ThorlundLehana Thabane
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
Apr 26, 2013·The New England Journal of Medicine·Qun LiZijian Feng
Apr 30, 2014·The Journal of Antimicrobial Chemotherapy·E Bart TarbetSimon P Tucker
May 29, 2014·Current Opinion in Virology·Aeron C Hurt

❮ Previous
Next ❯

Citations

Sep 28, 2016·Protein Engineering, Design & Selection : PEDS·Shangfei ZhangShunyi Zhu
Apr 21, 2018·Archives of Insect Biochemistry and Physiology·Jing ZhouHui Ai
Dec 18, 2019·International Journal of Molecular Sciences·Min GuoChanglin Zhou

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.