Antiviral activity of pyridyl imidazolidinones against enterovirus 71 variants

Journal of Biomedical Science
Tzu-Chun ChenShin-Ru Shih

Abstract

Pyridyl imidazolidinone is a novel class of capsid binder which can inhibit enterovirus 71 (EV71). In this study, we tested the susceptibility of six recombinant viruses with different single-site mutations in VP1. Eleven modified pyridyl imidazolidinones were synthesized and used to probe the interaction between these compounds and the EV71 VP1 protein. We found that the D31N or E98K mutant viruses were susceptible to bulkier compounds, which suggested that mutations at these two sites in VP1 may widen the hydrophobic pocket of VP1, allowing bulkier compounds to enter and interfere VP1-receptor binding. Additionally, the Y116H mutant was more resistant to pyridyl imidazolidinone compounds containing a methyl group in the central position of the hydrophobic linker. When a trifluoromethyl group was substituted for the methyl group in the middle of the linker chain, the inhibitory effect was totally abolished in the Y116H mutant, suggesting that the interaction between Tyr (Y) 116 of VP1 and the central position of the linker chain of pyridyl imidazolodinone is very important for drug efficacy. A V192M mutant was resistant to most of the derivatives, indicating that residue 192 is a key mutation for resistance to pyridyl imidazol...Continue Reading

References

Mar 27, 1992·Science·J M BergelsonR W Finberg
Mar 10, 1989·Cell·J M GreveA McClelland
Nov 5, 1989·Journal of Molecular Biology·S S KimM A McKinlay
Dec 1, 1989·Antimicrobial Agents and Chemotherapy·M G WoodsM A McKinlay
Jan 1, 1989·Viral Immunology·M G Rossmann
Jan 1, 1989·Annual Review of Biochemistry·M G Rossmann, J E Johnson
Jul 1, 1988·The Pediatric Infectious Disease Journal·G L GilbertM Sneddon
Jun 1, 1985·Antimicrobial Agents and Chemotherapy·M J OttoM A McKinlay
Sep 27, 1985·Science·J M HogleD J Filman
Dec 1, 1985·Journal of Medicinal Chemistry·G D DianaC Oglesby
Sep 1, 1985·The Journal of Antimicrobial Chemotherapy·M A McKinlay
Apr 1, 1994·The Journal of Infectious Diseases·J P AlexanderL J Anderson
Jul 15, 1995·Structure·J K MuckelbauerM G Rossmann
Aug 10, 1999·The Pediatric Infectious Disease Journal·H A Rotbart
Sep 3, 1999·Antimicrobial Agents and Chemotherapy·D C PevearJ M Groarke
Sep 25, 1999·The New England Journal of Medicine·M HoS R Shih
Dec 23, 1999·The Pediatric Infectious Disease Journal·M H Sawyer
Feb 5, 2000·The New England Journal of Medicine·S AbuBakarS K Lam
Feb 15, 2001·Expert Opinion on Investigational Drugs·J R Romero
Aug 26, 2004·Antimicrobial Agents and Chemotherapy·Shin-Ru ShihYu-Sheng Chao
Sep 24, 2004·Bioorganic & Medicinal Chemistry Letters·Jyh-Haur ChernShin-Ru Shih

❮ Previous
Next ❯

Citations

Oct 22, 2008·The Journal of Antimicrobial Chemotherapy·Tzu-Chun ChenShin-Ru Shih
Jan 22, 2010·The Journal of Antimicrobial Chemotherapy·Hui-Chen HungChing-Ping Tseng
Feb 2, 2010·The Pediatric Infectious Disease Journal·Ta-Chung LeeKow-Tong Chen
Feb 14, 2014·Journal of Biomedical Science·Chee Wah TanYoke Fun Chan
Feb 25, 2014·Journal of Microbiology, Immunology, and Infection = Wei Mian Yu Gan Ran Za Zhi·Hamid Reza Pourianfar, Lara Grollo
Mar 28, 2012·Biochemical and Biophysical Research Communications·Juan XuShan Lu
Jun 10, 2011·Critical Reviews in Microbiology·Lina YiMing-Liang He
Apr 22, 2016·The Journal of Antimicrobial Chemotherapy·Jin-Yuan HoJim-Tong Horng
Oct 19, 2010·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Yan WuVincent T K Chow
Oct 27, 2010·Drug Discovery Today·Kan X WuJustin J H Chu
Jan 3, 2019·ChemMedChem·Sharada Prasanna Swain, Sandeep Mohanty
Sep 5, 2019·Journal of Biomedical Science·Jing-Yi LinShin-Ru Shih
Apr 16, 2020·BMC Complementary Medicine and Therapies·Salima S LalaniChit Laa Poh
May 8, 2021·Scientific Reports·Yong Wah TanJustin Jang Hann Chu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

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

Antimicrobial Resistance (ASM)

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

Antimicrobial Resistance

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

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Allergy & Infectious Diseases (ASM)

Allergies result from the hyperreactivity of the immune system to some environmental substance and can be life-threatening. Infectious diseases are caused by organisms including bacteria, viruses, fungi and parasites. They can be transmitted different ways, such as person-to-person. Here is the latest research on allergy and infectious diseases.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antivirals (ASM)

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

Allergy & Infectious Diseases

Allergies result from the hyperreactivity of the immune system to some environmental substance and can be life-threatening. Infectious diseases are caused by organisms including bacteria, viruses, fungi and parasites. They can be transmitted different ways, such as person-to-person. Here is the latest research on allergy and infectious diseases.