GVN Center and Member Spotlight

September 11, 2020 – GVN SPOTLIGHT ON:

Dr. Raymond Schinazi
Frances Winship Walters Professor of Pediatrics
Director of the Laboratory of Biochemical Pharmacology
Co-Director of the HIV Cure Scientific Working Group within the NIH-sponsored Emory University Center for AIDS Research (CFAR) in Atlanta, Georgia, USA

What are you and your institution currently working on regarding COVID-19?

Emory is one of the few institutions that has proven strengths in drug discovery and development and vaccine/immunology research. It is rich with faculty that innovate and educate young minds. The response to the COVID-19 pandemic has been amazing. As of September 10, our faculty have published 366 peer reviewed papers on COVID-19 and garnered over $80 million in Covid-19 extramural funding. Research is proceeding on vaccines, therapeutics, diagnostics, apps and tools, surveillance, modeling, health impact and many other initiatives. Of significance Emory received the largest award from the NIH in a single budgetary year to evaluate and rapidly create accessible diagnostic tools and tests. Having a primate center allows us to study vaccines, pathogenesis and drugs in rhesus monkeys infected with COVID-19. 

Please, further describe your research in the testing affecting immunity and inflammation, identification of protease inhibitors, nucleoside analogs, repurposed drugs and animal models for COVID-19:

Our research focuses on the development of innovative drugs, such as protease inhibitors and nucleoside analogs for SARS-CoV-2. We also have a program on repurposed drugs, including JAK inhibitors, which led to in a controlled randomized human clinical trial of baricitinib with or without remdesivir involving over 1,000 patients with moderate to severe COVID-19. Baricitinib could provide a dual effect of dampening inflammation and reducing viral replication. We have studied this drug in rhesus macaques and in different cell culture system. We have also used a very unique organotypic model of human lung inflammation features with differentiated air-liquid interface (ALI) cultures of human lung epithelium that are grown on lamina propria-like scaffolds. This system enables massive recruitment of primary human blood leukocytes in the lumen, unlike typical Transwell models, and also enables controlled apical (or basal) exposure to viruses. We are applying this model to evaluate various potential anti-SARS-CoV-2 drugs as well as the issue of co-infection of SARS-CoV-2 and other respiratory viruses. We also have programs in cardiology to elucidate the effect of donor variation on susceptibility of cardiomyocytes to SARS-CoV-2 infection by using our human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) model system and by using our established drug discovery program to identify effective and safe therapeutic strategies to reduce or to eliminate these cardiac complications. In addition, we are involved in the NIH sponsored RADx program to evaluate novel rapid diagnostic tools for SARS-CoV-2. Furthermore, we are working on understanding the impact of CoV-2 on the brain as well as the short and long-term impacts of COVID-19 on mental health.

Emory University leads the new federally funded clinical trials network to centralize efforts to prevent COVID-19. The network links four existing NIAID-funded clinical trial networks, including the Infectious Diseases Clinical Research Consortium (IDCRC) based at Emory. The COVID Prevention Trials Network (COVPN) will focus on large Phase 3 clinical trials for the disease and will be responsible for enrolling thousands of volunteers to participate in the large-scale clinical testing of multiple investigational vaccines and monoclonal antibodies intended to protect people from COVID-19. For additional information please go to: https://news.emory.edu/stories/2020/06/coronavirus_research_at_emory/

 

Professional Summary

Dr. Schinazi directs the Laboratory of Biochemical Pharmacology (LOBP) that uses a multidisciplinary approach to develop and test antiviral agents that could be used for the treatment life-threatening viral infections. In this respect, the major research emphasis of the LOBP is two-fold: 1) the development of antiviral agents for the treatment of infections caused by HIV, hepatitis viruses (HBV, HCV), Yellow Fever, Chikungunya, Coronavirus, Mayarovirus, herpesviruses and Dengue virus; 2) strategies to eradicate viral reservoirs of HIV-1, HBV and other critical human viral pathogens using novel therapeutic strategies. Work involves molecular modeling, synthetic, biochemical, pharmacological, and molecular genetic approaches, including gene therapy and site-directed mutagenesis. The main objective is to develop pre-clinical, in-house compounds for the prevention, treatment and cure of these important pathogens. Areas of particular interest include the phenotypic and genotypic characterization of drug-resistant virus variants and ways to overcome resistant viruses using combinations of antiviral drugs. Five compounds developed by this group have been approved by the US FDA for the treatment of HIV-1 and/or HBV infections saving millions of lives. Currently, their multidisciplinary antiviral research program is focused on discovering agents that could be used for eliminate HIV, hepatitis B infections, CoV-2 and Yellow fever. The LOBP also has also been a site for training international scientists to obtain training on a shorter basis in specific areas of antiviral discovery, structure, resistance, and pharmacology. Schinazi is the founder of several biotechnology companies focusing on antiviral drug discovery and development, including Pharmasset Inc (acquired by Gilead), Triangle Pharmaceuticals (acquired by Gilead), Idenix Pharmaceuticals (acquired by Merck), and RFS Pharma LLC (now called Cocrystal). He has published over 560 papers and reviews and holds more than 100 US patents. He is best known for his work on d4T (stavudine), 3TC (lamivudine), FTC (emtriva) and SOF (sofosbuvir). His inventions now sell more than US $5.0 billion per year and more than 94% of HIV-infected individuals take at least one of the drugs he invented.

About Emory School of Medicine, Pharmacology and Chemical Biology

We are proud to be celebrating 90 years of discovery, training, leadership, and impact!  The leadership of past chairs and the efforts of outstanding faculty and trainees have shaped our department into one of the leading pharmacology research and education programs in the nation. Our research has uncovered the molecular basis for the action of pharmacological agents and revealed actionable targets for new drug discovery. In addition, our faculty have impacted the growth and success of the pharmacology field by contributing five presidents of the American Society for Pharmacology and Experimental Biology (ASPET), and six Editors of ASPET journals. Our trainees have flourished across the nation and the world, becoming academic, industry, and government thought leaders, biomedical scientists and managers, and vibrant entrepreneurs.

In recognition of the exciting new possibilities that today’s biomedical research landscape offers for discovery, innovation and education, our faculty together developed a new vision for the department in 2017: we are extending our outstanding molecular pharmacology research programs to advance therapeutics innovation and translational biology. Accordingly, in 2019 we changed our name the “Department of Pharmacology and Chemical Biology”. This change reflects a broadening of vision, from one that centered primarily on the fundamental science of drugs, to one that now also includes the development of tools (e.g., chemical probes) with which to understand biology and ultimately treat new diseases. Traditional pharmacology examines drugs’ mechanism of action and their metabolism and safety, while chemical biology is oriented toward dissecting the machinery of life using chemical probes. Such insights will in turn help us to advance our understanding of human diseases and to design better medicines. As summarized by Vikas Sukhatme, MD, ScD, Dean of the Emory University School of Medicine, “This is more than just a name change. It reflects Pharmacology and Chemical Biology’s capabilities as discovery engines connecting the medical school and university.”  We see ourselves as an “interface department”, connecting basic biomedical discovery and clinical advances to promote educational and therapeutic innovation activities.

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