Experience

• Merck 

  • • Principal Scientist, High Content Imaging, Quantitative Biosciences  /   Nov 2018 - Present · 3 yrs 4 mos  /   Boston, MA

      1. • Leading imaging group at Cellular Pharmacology to enhance imaging capabilities at the department of Quantitative Biosciences

         • Integrating new imaging approaches like Cell Painting and 3D imaging including assay design, data flow, and data analysis into the drug discovery process for oncology, neuroscience, and immunology therapeutic areas.

         • Building up collaborations with HPC data analytics focusing on Deep Learning Image analysis.

         • Leading imaging group at Cellular Pharmacology to enhance imaging capabilities at the department of Quantitative Biosciences • Integrating new imaging approaches like Cell Painting and 3D imaging including assay design, data flow, and data analysis into the drug discovery process for oncology, neuroscience, and immunology therapeutic areas. • Building up collaborations with HPC data analytics focusing on Deep Learning Image analysis.

• Hanry M.Jackson Foundation for Advancement of Military Medicine; BCSAI, USAMRIID

  • • [Principal Investigator]  /   Jul 2013 - Nov 2018 · 5 yrs 5 mos  /   Fort Detrick, MD

      1. • As a lead of in vitro testing for anti-viral and anti-toxin discovery projects established collaborations on 80 projects (currently) with major pharmaceutical companies, biotech and academic organizations on the search for anti-viral therapies against major DoD viral threats and emerging pathogens including Filoviridae, Togaviridae, Bunyaviridae, Arenaviridae, Flaviviridae, Picornoviridae, Coronaviridae, Paramixaviridae ets.

         • Developed comprehensive phenotypic screening triage for efficient discovery of new active compounds and fast and evaluation of their potency and selectivity for using confocal imaging PE Opera platform.

         • Developed screening triage to search of inhibitors of Botulinum neurotoxin both whole enzyme and active side using Fluorescent Imaging and MSD technology platforms. Performed screening and hit to lead characterization for selected collections both inter- and extra-mural collaborations

         • On a daily bases coordinate work of screening group (7 people) applying high content imaging in antiviral drug discovery and supporting research lab of 1 PhD scientist (currently) for enzymatic in vitro testing.

         • Provide data analysis and data packages designed for rapid prioritization of potent and selective antiviral therapies for rapid transition into in vivo evaluation, report results for collaborators and financial agencies.

         • As a lead of in vitro testing for anti-viral and anti-toxin discovery projects established collaborations on 80 projects (currently) with major pharmaceutical companies, biotech and academic organizations on the search for anti-viral therapies against major DoD viral threats and emerging pathogens including Filoviridae, Togaviridae, Bunyaviridae, Arenaviridae, Flaviviridae, Picornoviridae, Coronaviridae, Paramixaviridae ets. Developed comprehensive phenotypic screening triage for efficient discovery of new active compounds and fast and evaluation of their potency and selectivity for using confocal imaging PE Opera platform. Developed screening triage to search of inhibitors of Botulinum neurotoxin both whole enzyme and active side using Fluorescent Imaging and MSD technology platforms. Performed screening and hit to lead characterization for selected collections both inter- and extra-mural collaborations On a daily bases coordinate work of screening group (7 people) applying high content imaging in antiviral drug discovery and supporting research lab of 1 PhD scientist (currently) for enzymatic in vitro testing. Provide data analysis and data packages designed for rapid prioritization of potent and selective antiviral therapies for rapid transition into in vivo evaluation, report results for collaborators and financial agencies.

• IP-Korea

  • • Director of CCT (Center of Core Technologies)  /   Mar 2010 - Jun 2013 · 3 yrs 4 mos  /   Institut Pasteur Korea

      1. • Accountable for project managing of three image based core platforms: PhenomicScreen, PhenomicID and Phenomic drug-target de-convolution. The Center comprises 20 people including 4 PhD-level scientists and 5 PhD students organized into three groups: Screening Technology, Discovery Biology and Image Mining.

         • Accountable for project managing of three image based core platforms: PhenomicScreen, PhenomicID and Phenomic drug-target de-convolution. The Center comprises 20 people including 4 PhD-level scientists and 5 PhD students organized into three groups: Screening Technology, Discovery Biology and Image Mining.

• Pfizer Pharmaceuticals

  • • Principal Research Scientist II  /   Jan 2009 - Mar 2010 · 1 yr 3 mos

      1. • As a Group Leader of Cellular Assay Development, organized, trained and supervised a group of 5 scientists working on cell-based assay development for Screening Sciences at Wyeth; coordinated the workflow for assay development and interacted with research group, HTS and automated cell culture group to deliver TS ready cell based assays.

         • As a Group Leader of Cellular Assay Development, organized, trained and supervised a group of 5 scientists working on cell-based assay development for Screening Sciences at Wyeth; coordinated the workflow for assay development and interacted with research group, HTS and automated cell culture group to deliver TS ready cell based assays.

• Wyeth Research

  • • Principal Scientist  /   2002 - 2009 · 7 yrs

      1. • Ran drug discovery projects for the Pharmaceutical Industry. Targets included GPCRs (neuroscience and inflammation), ion channels and transporters (inflammation, metabolic diseases, and neuroscience), kinases and receptors, cell signaling pathways, cellular enzymes (oncology). During 9 years I developed 52 fully characterized cell-based assays. Assays technologies included FLIPR-based, EFC DiscoverX , HTRF CisBio, MDS Transfluor, immuno-staining HCS technologies. I developed multiple assays for SAR, profiling and hit selection; 10 functional follow up HCS assays for PE Opera and Cellomics Array Scan VTI and additionally performed several low scale profiling and secondary screens.

         • Worked with HTS scientists on development and custom design of HSDM Thermo/duel FLIPR(tetra) Automated system (Reflected by publication in JALA, 2006 ). Evaluated and integrated (working with our HTS group, Thermo and PE) new technologies: first FLIPR-3-based assays, new fully automated platforms for FLIPR Tetra , PE Opera for first HCS project at Screening Sciences. Evaluated and integrated image-based technologies (PE/Evotec Opera confocal system, Cellomics Array ScanVTI, FCS Guava EasyCyte and Essen IncuCyte.

• Purpose of the study: Antiviral agent development.  Clinical care for Zika virus infection is supportive, and there are no prophylactic or therapeutic drugs, vaccines, or other biologicals licensed for use to prevent or treat Zika virus infection and disease. A Zika virus threat assessment and evaluation of medical countermeasure development options has been completed; re-purposing existing licensed drugs was identified as the most efficient strategy for rapid development of licensed medical countermeasures suitable for prevention, treatment, or containment of the pathogen (1,2).

• Methods/summarized description of the project: Hypothesis-driven high throughput re-purposed drug screening.  An iterative multi-step drug selection and screening algorithm was established; 1) drug targets involving inhibition of virus-host cell interactions were identified, 2) compounds with significant clinical pharmacokinetic and safety data (preferably including in pregnancy) which inhibit the pathways were selected, 3) selected pharmaceuticals were tested for inhibition of Zika virus infection and replication using multiple cell types and Zika viral isolates, 4) pharmaceuticals with single-digit micromolar to nanomolar IC50 and CC50/IC50 ratios consistent with anti-viral specificity were selected for subsequent development as prophylactic and therapeutic anti-Zika drug candidates. 

• Results:  Re-purposed licensed drugs with anti-Zika activity which are safe for use in pregnancy. Three general mechanisms of action (including autophagy inhibition) have been identified and corresponding compounds have been screened.  Multiple re-purposed drugs have been identified which meet selection criteria for subsequent development. 

• Conclusion: Hypothesis-driven high throughput re-purposed drug selection can expedite identification of emerging infectious disease medical countermeasure candidates.  A summary of the pathways targeted, drugs identified and viral inhibition results obtained will be presented. 

• Discussion: Zika infection of the recipient host requires viral envelope protein binding and particle uptake into susceptible cells, is mediated by specific receptors which include DC-SIGN, AXL, Tyro3, and TIM-1, and triggers transcriptional activation of Toll-like receptor 3 (TLR3), RIG-I, MDA5, interferon stimulated genes including OAS2, ISG15, and MX1, and beta interferon (4). Primarily infected cells include skin fibroblasts, epidermal keratinocytes, and skin dendritic cells. Zika virus subsequently exploits autophagy to facilitate uptake and replication8, and pharmacologic manipulation of Zika infected cells with 3-Methyladenine (3-MA), an inhibitor of autophagosome formation, strongly reduces viral copy numbers in infected fibroblasts (3). Based on prior murine studies involving Zika virus inoculation in mouse brain (5), autophagy of Zika virus has been postulated as playing a key role in the pathogenesis of Zika-associated primary microcephaly (6).  Pharmacological mechanisms of currently licensed 4-Aminoquinoline anti-malarial drugs include inhibition of autophagy and broad-spectrum cathepsin B-mediated inhibition of viruses which require endosomal acidification (7).

References:

•  1. Malone RW, Homan J, Callahan MV, Glasspool-Malone J, Damodaran L, Schneider Ade B, Zimler R, Talton J, Cobb RR, Ruzic I, Smith-Gagen J, Janies D, Wilson J; Zika Response Working Group.  Zika Virus: Medical Countermeasure Development Challenges.  PLoS Negl Trop Dis. 2016 Mar 2;10(3):e0004530. doi: 10.1371/journal.pntd.0004530. PMID: 26934531

• 2. Longini IM Jr, Nizam A, Xu S, Ungchusak K, Hanshaoworakul W, Cummings DA, Halloran ME.  Containing pandemic influenza at the source.  Science. 2005 Aug 12;309(5737):1083-7. PMID: 16079251

• 3. Hamel R, Dejarnac O, Wichit S, Ekchariyawat P, Neyret A, Luplertlop N, et al. Biology of Zika Virus Infection in Human Skin Cells. J Virol. 2015; 89(17):8880–96. doi: 10.1128/JVI.00354-15 PMID: 26085147.

• 4. Carneiro LA, Travassos LH. Autophagy and viral diseases transmitted by Aedes aegypti and Aedesalbopictus. Microbes Infect. 2016. doi: 10.1016/j.micinf.2015.12.006 PMID: 26774331.

• 5. Bell TM, Field EJ, Narang HK. Zika virus infection of the central nervous system of mice. Arch Gesamte Virusforsch. 1971; 35(2):183–93. PMID: 5002906.

• 6. Tetro JA. Zika and microcephaly: Causation, correlation, or coincidence? Microbes Infect. 2016. doi: 10.1016/j.micinf.2015.12.010 PMID: 26774330.

• 7. Zilbermintz L, Leonardi W, Jeong SY, Sjodt M, McComb R, Ho CL, Retterer C, Gharaibeh D, Zamani R, Soloveva V, Bavari S, Levitin A, West J, Bradley KA, Clubb R3, Cohen SN, Gupta V, Martchenko M. Identification of agents effective against multiple toxins and viruses by host-oriented cell targeting.  Sci Rep. 2015 Aug 27;5:13476. doi: 10.1038/srep13476. PMID: 26310922

Special Issue "Emerging Viruses and Antiviral Drugs"

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Virology".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 7000

Special Issue Editors

1. Dr. Veronica Soloveva  /   Guest Editor

   1. • Department of Quantitative Biosciences, Merck, Boston, MA, USA

      • Interests: Antiviral drug discovery; Phenotypic drug discovery; HCI

2. Dr. Miguel A. Martín-Acebes /   Guest Editor

   1. • Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Carretera de A Coruña Km 7.5, 28040 Madrid, Spain

      • Interests: virus; arbovirus; flavivirus; dengue; West Nile; Zika; zoonoses; lipid; virus-host interaction; sphingolipids; fatty acids; metabolism; antivirals; vaccines

3. Dr. Sina Bavari  /   Guest Editor

   1. • CSO, Co-Founder of Healion Bio, Frederick, MD, USA

      • Interests: virology; oncology; drug discovery; drug development

Special Issue Information

Dear Colleagues,

Emerging viruses are a very broad category that includes not only newly discovered viruses but also re-emerging variants of known viruses. These viruses continue to cause mass disruption by creating constant threat to public health. In the last 20 years, we have observed a variety of viral outbreaks, such as severe acute respiratory symptom (SARS), H1N1 influenza, Ebola virus, Middle East respiratory syndrome coronavirus (MERS-CoV), Rift Valley fever, Crimean Congo hemorrhagic fever, Nipah and Hendra viruses, severe fever with thrombocytopenia syndrome virus (SFTSV), yellow fever virus (YFV), Zika virus, and the ongoing SARS-CoV-2. The globalization of the economies and quick-paced traveling patterns of human populations, combined with climate change, are creating ample opportunities for mass spread of viral infections. The multiple surges of SARS-CoV-2 variants have quickly exposed the challenges and limitations of vaccines and various antiviral treatments. For example, SARS-CoV-2 virus transmission has proven difficult to manage with current vaccines and therapeutic approaches. There is a strong need to position immune modulating modalities and other novel antivirals to suppress viral transmission and infection by inhibiting cellular pathways essential for viral infection.  The development of broad-spectrum antiviral drugs can provide an additional level of defense while specific antivirals are being developed. This approach has shown some indication of success against SARS-CoV-2 and may be appropriate to be implemented for future emerging viruses. This Special Issue, “Emerging Viruses and Antiviral Drugs”, focuses on various antiviral approaches to manage emerging and re-emerging viruses and will include antiviral drug discovery, discovery of the mechanism of actions, new targets, and upcoming and established technologies used for discovery and development of antiviral drugs.

Dr. Veronica Soloveva
Dr. Miguel A. Martín-Acebes
Dr. Sina Bavari
Guest Editors

Manuscript Submission Information [...]