Programs at the EIDD

The Emory Institute for Drug Development (EIDD) supports programs focused on the development of therapeutics for infectious diseases.

EIDD leadership has a long and successful track record of discovering and developing antiviral medications and this experience, coupled with a talented group of research scientists and ample physical assets, provides a strong foundation for the discovery and development of the next generation of antiviral therapeutics. Currently, we are directing our efforts toward unmet medical needs and rapid responses to emerging infectious disease threats. Specifically, we are targeting a selected set of RNA viruses which, as a class, are responsible for 80% of the global viral burden.

The three projects summarized below are exemplary of the programs we are currently pursuing.

Collaborator – Prof. Mark Buller, Saint Louis University

Over the last two decades, competitive alternative substrate inhibitors of the virally encoded RdRps have become a foundation for antiviral therapy for a number of clinically relevant pathogens including human immunodeficiency virus (HIV) infection, hepatitis B virus (HBV), cytomegalovirus (CMV) and herpes simplex virus (HSV). These compounds are typically nucleoside analogs or prodrug forms of nucleotide analogs. Two such inhibitors, Emtriva® and Epivir® were invented at Emory University by Dennis Liotta, among others, and have become key components of the cocktail of drugs typically prescribed to treat HIV infections.

We are currently developing a new generation of ribonucleoside and ribonucleotide analogs to treat unmet and emerging pathogenic infections. Toward this end, we are focusing our considerable expertise and in-house capabilities on a number of currently relevant pathogens and objectives which include:

Nucleoside Analogs to Treat Infections by the Flaviviridae Family of Viruses

We are designing analogs to treat Dengue virus infection, which affect 100 million people annually world-wide, and is widely considered to be an emerging threat in the US. In a related project, Hepatitis C virus (HCV) continues to be a major problem throughout the US and abroad. There is currently a great deal of research and development throughout academia and industry to identify new effective treatments. Accordingly, we are optimizing a set of ribonucleoside and ribonucleotide analogs that are specifically designed to deliver effective concentrations of active ribonucleotides to HCV infected liver tissue.

Nucleoside Analogs to Treat Infections by the Alphavirus Family of Viruses

Collaborator - Prof. Mark Buller, Saint Louis University

Funding – Defense Threat Reduction Agency

Specific members of the Alphavirus family, Eastern Equine Encephalitis (EEEV), Western Equine Encephalitis (WEEV), and Venezuelan Equine Encephalitis (VEEV), can cause life threatening inflammation in brain and other CNS tissues. These are pathogens that are endemic to many parts of the world that are of specific concern to the US military that must operate in many such affected areas. As such, we have recently received support from the Defense Threat Reduction Agency (DTRA) to identity active, ribonucleoside based leads that effectively inhibit the replication cycle of these pathogens.

Additional Pathogens Currently Being Targeted

  • Bunyaviridae - Hanta virus
  • Coronaviradae - SARS, MERS

Collaborator – Prof. Richard Plemper, GA State University

Since the onset of antiviral therapy, small molecule therapeutics have provided pronounced clinical benefits for disease management and prevention. However, traditional antiviral approaches are frequently compromised by a narrow pathogen target range for individual antivirals and the development of drug resistance in circulating viral pools. To address these problems on a systemic level, we are optimizing a set of lead compounds that target host cell proteins that are required for viral replication. Our goal is to develop a small molecule therapeutic with a broadened antiviral target spectrum against multiple members of the myxovirus family.

Consistent with this notion, we observe an expanded target range with our lead compound classes, thus moving beyond the traditional "one-bug one-drug" scenario of many antiviral strategies. The lead developmental candidate class is well tolerated and demonstrates low nanomolar potency against clinically relevant priority pathogens of the ortho- and paramyxovirus families. We hypothesize that viruses predominantly associated with acute disease, as observed in the case of most myxovirus infections, constitute ideal targets for a host directed antiviral approach since treatment time, and thus potential side effects of long-term host exposure to the drug, remain limited. Current specific targets within this program include Respiratory Syncytial Virus (RSV), Influenza A, Nipah virus and Mumps virus.

Collaborator – Prof. Richard Plemper, GA State University

A screening effort in a cell based assay using the measles virus as a representative of the myxovirus family generated a potent hit that proved to be a inhibitor of the virally encoded RdRp. This hit was later optimized to reveal EPRX-0519 which is orally efficacious with an acceptable in vivo safety profile. We are currently continuing to advance this compound and investigate both its efficacy and resistance profiles for measles and canine distemper.

View Relevant Publications