Enteroviruses are small, non-enveloped RNA viruses responsible for poliomyelitis, encephalitis, acute heart failure or severe hepatitis in newborns, and other life threatening infections. In the United States recent outbreaks of coxsackievirus B1 (CVB1) infections and coxsackievirus A6 served as reminders of the ongoing threat raised by these pathogens. Similarly, outbreaks of enterovirus 71 have occurred nearly annually in Europe and the Asia-Pacific region for almost 20 years, and could potentially lead to epidemics in North America if imported. We have recently identified a novel group of closely related small molecules that inhibit the replication of coxsackievirus B (CVB) variants, polioviruses, and other enteroviruses. We propose a two-year study to identify derivatives of this group of compounds with robust antiviral activity against pathogenic enteroviruses. Successful completion of these goals could ultimately lead to the development of antiviral drugs useful in cases of life-threatening enterovirus infections and that could potentially play a role in the eradication of poliovirus circulation.

Public Health Relevance

Enteroviruses cause severe infections of the heart, sepsis in newborn infants, respiratory tract infections, and other diseases. No medications currently exist to treat these infections. We have identified unique molecules that could potentially be developed into medications, and propose a study to clarify their power against other enteroviruses and identify how they work.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI107383-02
Application #
8870292
Study Section
Drug Discovery and Mechanisms of Antimicrobial Resistance Study Section (DDR)
Program Officer
Dempsey, Walla L
Project Start
2014-06-15
Project End
2016-05-31
Budget Start
2015-06-01
Budget End
2016-05-31
Support Year
2
Fiscal Year
2015
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Pediatrics
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Zuo, Jun; Kye, Steve; Quinn, Kevin K et al. (2015) Discovery of Structurally Diverse Small-Molecule Compounds with Broad Antiviral Activity against Enteroviruses. Antimicrob Agents Chemother 60:1615-26