GVN Center and Member Spotlight
Professor, Department of Microbiology
Director of the Global Health and Emerging Pathogens Institute
Icahn School of Medicine at Mount Sinai in New York, USA
What are you and your institution currently working on regarding COVID-19?
My lab, together with the Palese and Krammer laboratories, are developing a Newcastle Disease virus (NDV) based-COVID-19 vaccine. The NDV platform is currently carrying the 6-proline stabilized, cleavage-site deleted spike (Hexapro) of the parental SARS-CoV-2 virus (NDV-HXP-S). NDV-HXP-S is an egg-based, whole chimeric Newcastle disease virus (NDV) expressing membrane anchored pre-fusion-stabilized trimeric SARS-CoV-2 spike protein. This vaccine is easy to manufacture in large amounts and highly stable. Preclinical development of the vaccine is close to completion and we are preparing to start phase 1/2 studies. We believe that the NDV platform is an ideal approach to prevent COVID-19 as well as next generation COVID variant vaccines.
Are there other aspects of your research on SARS-CoV-2 that you feel excited about?
We have been working together with numerus collaborators to identify druggable host factors required for SARS-CoV-2 replication. Out of these studies, we are particularly excited about one drug, plitidepsin, that is approved for the treatment of myeloma multiple in Australia, and that targets a host factor, eEF1A, whose activity is essential for virus production. The drug is very potent in human primary human cells and in mice in inhibiting replication of SARS-CoV-2 and in preventing disease. Results on phase 1/2 clinical trials have been completed and are in the process of final evaluation, with phase 3 clinical trials already under evaluation.
White KM, Rosales R, Yildiz S, Kehrer T, Miorin L, Moreno E, Jangra S, Uccellini MB, Rathnasinghe R, Coughlan L, Martinez-Romero C, Batra J, Rojc A, Bouhaddou M, Fabius JM, Obernier K, Dejosez M, Guillén MJ, Losada A, Avilés P, Schotsaert M, Zwaka T, Vignuzzi M, Shokat KM, Krogan NJ, García-Sastre A. Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A. Science. 2021 Jan 25:eabf4058. doi: 10.1126/science.abf4058.
Dr. García-Sastre is Professor in the Department of Microbiology and Director of the Global Health and Emerging Pathogens Institute of Icahn School of Medicine at Mount Sinai in New York. For the past 30 years, his research interest has been focused on the molecular biology of influenza viruses and several other negative strand RNA viruses. During his post-doctoral training in the early 1990s, he developed, for the first time, novel strategies for expression of foreign antigens by a negative strand RNA virus, influenza virus. He has made major contributions to the influenza virus field, including 1) the development of reverse genetics techniques allowing the generation of recombinant influenza viruses from plasmid DNA, (studies in collaboration with Dr. Palese); 2) the generation and evaluation of negative strand RNA virus vectors as potential vaccine candidates against different infectious diseases, including malaria and AIDS, and 3) the identification of the biological role of the non-structural protein NS1 of influenza virus during infection: the inhibition of the type I interferon (IFN) system.
His studies provided the first description and molecular analysis of a viral-encoded IFN antagonist among negative strand RNA viruses. These studies led to the generation of attenuated influenza viruses containing defined mutations in their IFN antagonist protein that might prove to be optimal live vaccines against influenza. His research has resulted in more than 600 scientific publications and reviews. Dr. García-Sastre is the director of the Center for Research on Influenza Pathogenesis (CRIP), one of the five NIAID funded Centers of Excellence for Influenza Research and Surveillance. He was among the first members of the Vaccine Study Section and member of the Virology B Study Section of NIH. In addition, he has served for 5 years as Editor of Journal of Experimental Medicine, and as Editor of Journal of Virology and Virus Research, he is Editor of PLoS Pathogens, and he is member of the Editorial Board of Vaccine, NPJ Vaccines, Emerging Microbes and Infection, and Influenza and Other Respiratory Diseases. He is a member of the scientific advisory board of Keystone Symposia. He has been a co-organizer of the international course on Viral Vectors (2001), held in Heidelberg, Germany, sponsored by Federation of European Biochemical Societies (FEBS), and of the first Research Conference on Orthomyxoviruses in 2001, held in Teixel, The Netherlands, sponsored by the European Scientific Working Group on Influenza (ESWI).
He has also been a co-organizing of the 7th International Society for Vaccines meeting in 2013, and of Keystone Meetings in 2014 on Respiratory Virus Pathogenesis and in 2017 on Interferons. His publication in Science on the reconstruction and characterization of the pandemic influenza virus of 1918 has been awarded with the distinction of the paper of the year 2005 by Lancet. In 2005, he became a Fellow of the American Academy of Microbiology, and in 2009, he received the Beijerink Professorship from the National Academy of Sciences of the Netherlands. In 2011, he has been elected President of the International Society for Vaccines, for 2014 and 2015. In 2017, he has been elected a fellow of the Royal Academy of Pharmacy in Spain. In 2019, he was recognized with a Honorary Doctor Degree from the University of Burgos, Spain. Also in 2019, he was elected a fellow of the National Academy of Sciences and of the National Academy of Inventors.
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