Molecular Virology

moriaki iologia

The main activity of the Molecular Virology research team of Dr. Niki Vassilaki is the study of the molecular biology of the Flaviviridae viruses HCV (Hepatitis C), DENV (Dengue), YFV (Yellow Fever) and ZIKV (Zika), of the Hepadnavirus HBV and of the Coronavirus SARS-CoV2, with main focus on mechanisms of viral replication and pathogenesis as well as on molecular mechanisms of action of replication inhibitors. For this purpose, the team has implemented viral subgenomic and infectious cell-culture based systems and has developed infectious models simulating normoxic and metabolic conditions of tissues. Moreover, human samples from different tissues of infected individuals are analyzed. More specifically, the team studies:

  • The association of Flaviviridae viruses (HCV, DENV, YFV) and HBV replication with oxygen signaling and the role of this interaction in viral pathogenesis and in the efficacy of direct-acting anti-virals

Vassilaki et al. J Virol. 2013; Vassilaki N. and Frakolaki E. Microbes Infect. 2017; Frakolaki et al. Cells. 2018; Frakolaki et al. Institut Pasteur International Network Symposium 2016

  • The association of Flaviviridae viruses (HCV, DENV) infections with the dopamine biosynthetic enzyme L-Dopa Decarboxylase, which has been recently identified as a PI3K binding partner and implicated in cell apoptosis. The role of DDC in DENV-virus induced cell death.

The interaction of catecholamine biosynthesis, metabolism and uptake with HCV and DENV replication.

Vassiliou et al. Biochimie 2019; Frakolaki et al. Cells 2019; Mprekoulis et al. Viruses 2021

  • The importance of the catecholamine biosynthesis and metabolism in the pathogenesis of SARS-CoV-2 and COVID-19 severity

Mpekoulis et al. PLoS One. 2021

  • The antibody responses following COVID-19 vaccination in Greek population

Vassilaki et al. Microorganisms. 2021

  • The anti-viral activity and mechanisms of action of lipophilic heterocyclic chelating agents, broadly active against Flaviviridae viruses (HCV, DENV, YFV, ZIKV)

Giannakopoulou et al. MedChemComm 2019; Frakolaki et al. 33rd International Conference on Antiviral Research (ICAR) 2020

  • Novel potent and safe HCV inhibitors from collections of synthetic analogues and natural products and characterization of their mechanisms of action. Zoidis et al. MedChemComm 2016; Lougiakis et al. Chem Biol Drug Des 2107; Ramsis et al. Arch Pharm 2018; Leila et al. ACS Omega 2019; Abdel Karim et al. Bioorg Chem. 2020; Mousa et al. Pharmaceuticals, 2021; Ahmed et al. MDPI 2020; Abdallah et al. accepted in Eur J Med Chem
  • The anti-HBV activity and mechanisms of action of new substituted imidazo[4,5-b]pyridines.

Gerasi et al. Bioorg Chem. 2020

  • Alternative translation initiation mechanisms of the HCV core+1 open reading frame, overlapping the core encoding region, including the expression of the HCV core+1/ARFP short protein, in cultured human hepatocytes. Study on its regulatory role in viral pathogenesis. Vassilaki and Mavromara J Biol Chem 2003, Vassilaki et al. Febs J 2007, Vassilaki et al. Virus Res 2008, Vassilaki et al. J Gen Virol 2008, Boumlic et al Virus Res 2011, Kotta-Loizou I. et al. J Gen Virol. 2013; Vassilaki et al. Int J Mol Sci. 2020

Granted patent and Provisional Patent application

ΑStudying the metabolic basis of the interaction between intracellular oxygen tension and replication of hepatotropic viruses HCV, DENV, YFV and HBV, as well as the role of this interaction in viral pathogenesis

Developing hepatocyte culture-based infection models adapted at the median oxygen tension of liver microenvironment (3% v/v O2) and simulating the metabolic conditions of natural infection: a) we investigate the influence of low oxygen (liver normoxia) on viral replication, and b) we study the cellular metabolic pathways of glycolysis, creatine kinase B and lipid-metabolism implicated in this interaction in order to understand important determinants of infection outcome and identify new therapeutic targets.

PUBLICATIONS

  • Low oxygen tension enhances hepatitis C virus replication. Vassilaki N.*, Kalliampakou I., Kotta-Loizou I., Befani C., Liakos P., Simos G., Mentis A.F., Kalliaropoulos A., Doumba P.P., Smirlis D., Foka P., Bauhofer O., Poenisch M., Windisch M.P., Lee M.E., Koskinas J., Bartenschlager R. and Mavromara P.* J Virol. 2013, 87, 2935-48. doi: 10.1128/JVI.02534-12.
    * Corresponding authors
  • Virus-host interactions under hypoxia. Special issue: Effects of hypoxia on infection and host immune control. Vassilaki N.* and Frakolaki E. Microbes Infect. 2017, 19, 193-203. doi: 10.1016/j.micinf.2016.10.004.
    * Corresponding author
  • The Role of Tissue Oxygen Tension in Dengue Virus Replication. Frakolaki E., Kaimou P., Moraiti M., Kalliampakou K. I., Karampetsou K., Dotsika E. Liakos P., Vassilacopoulou D., Mavromara P., Bartenschlager R. and Vassilaki N.* Cells. 2018, 7(12), 241; doi: 10.3390/cells7120241. Special Issue Gene Regulation by HIFs during Hypoxia
    * Corresponding author

PRESENTATIONS in CONFERENCES

  • Institut Pasteur International Network Symposium 2016, “From basic science to biomarkers and tools in Global Health”. Paris, France, 29 Nov. – 2 Dec. 2016

Poster presentation: The interplay between hepatotropic viruses and liver normoxia determines viral levels and response to therapeutics

Frakolaki E., Giannakopoulou E., Feuillette-Cadenne Ν., Kaimou P., Niotis G., Bartenschlager R., Mavromara P., Zoidis G., Windisch M., Neuveut C. and Vassilaki N.

  • 68th Congress of the Hellenic Society of Biochemistry and Molecular Biology. Athens, Greece, 10-12 Nov. 2017
    Oral presentationDeveloping a novel infectious cell model of Flaviviridae viruses that simulates in vivo normoxic and metabolic microenvironment for the characterization of broadly effective antivirals
    Frakolaki E., Kaimou P., Niotis G., Dimitriou M., Giannakopoulou E., Pardali V., Myrianthopoulos V., Mikros E., Bartenschlager R., Mavromara P., Zoidis G. and Vassilaki N.

Β. Identifying new, safe and broadly effective inhibitors, synthetic or naturally-derived, against the Flaviviridae viruses HCV, DENV, YFV and ZIKV, as well as against HBV, and characterizing their molecular mechanism of action. We evaluate two chemical libraries: a) A series of lipophilic heterocyclic compounds, derivatives of the fungal metabolite flutamide (2,6-diketopiperazines) and acetohydroxamic acid analogues, structurally related to broad-spectrum chelators that have intrinsic selectivity for two-metal ions in the active site of nucleic acid-processing enzymes of HCV, HIV and influenza virus b) A group of natural products, including terpenes, steroids, alkaloids (indoles) and flavonoids, isolated from plants of Greek and Mediterranean that we have been previously identified as active against HCV replication, as well as synthetic derivatives. For this purpose, we employ efficient cell culure-based infectious and subgenomic viral systems and we have established infection models simulating normoxic and metabolic conditions of tissues. Collaboration with Prof. G. Zoidis and A. L. Skaltsounis (Faculty of Pharmacy, University of Athens).

C. Studying the activity and mode of action of novel tricyclic nucleosides against HCV RNA replication. Collaboration with Prof. P. Marakos and N. Pouli (Faculty of Pharmacy, University of Athens).

D. Evaluating a series of novel organic molecules, rationally designed to target the HCV non-structural protein NS5A, against different virus genotypes, in order to discover highly potent inhibitors with pangenotypic activity and improved profile. Collaboration with Prof. Dr. Ashraf H. Abadi (Faculty of Pharmacy and Biotechnology, German University in Cairo, Egypt).

PUBLICATIONS

  • Novel indole-flutimide heterocycles with activity against influenza PA endonuclease and hepatitis C virus. Zoidis G., Giannakopoulou E., Stevaert A., Frakolaki E., Myrianthopoulos V., Fytas G., Mavromara P., Mikros E., Bartenschlager R., Vassilaki Ν.* and Naesens L.* Chem. Comm. 2016, 7, 447-456. doi:10.1039/C5MD00439J.

* Principal investigators

     # Featured as: New Talent Europe, 2016 MedChemComm Hot Article, Front cover

  • Novel nucleoside analogues targeting HCV replication through an NS5A-dependent inhibition mechanism. Lougiakis N., Frakolaki E., Karmou P., Pouli N.*, Marakos P., Madan V., Bartenschlager R., Vassilaki N.* Chem Biol Drug Des. 2017, 90(3), 352-367.
    * Corresponding authors
  • Expanding the chemical space of anti-HCV NS5A inhibitors by stereochemical exchange and peptidomimetic approaches. Ramsis T.M., Abdel Karim S.E., Vassilaki N., Frakolaki E., Kamal A.A.M., Zoidis G., Ahmed N.S. and Abadi A.H. Arch Pharm (Weinheim)2018, 351(7):e1800017. doi: 10.1002/ardp.201800017.

PRESENTATIONS in CONFERENCES

  • 67th Panhellenic Conference of the Hellenic Society for Biochemistry and Molecular Biology. Ioannina, Greece, 25-27 Nov. 2016

Oral presentation: Mechanism of action of broadly effective inhibitors targeting hepaci- and flavivirus replication: Validation under liver normoxic conditions

Frakolaki E., Kaimou P., Kelepouras K., Giannakopoulou E., Myrianthopoulos V., Niotis G., Mikros E., Bartenschlager R., Mavromara P., Zoidis G. and Vassilaki N.

 

  • International Symposium on Hepatitis C Virus and Related Viruses. Dublin, Ireland, 8-11 Oct. 2018

Αναρτημένη παρουσίαση: Novel acetohydroxamic metal-chelators targeting the replication of Flaviviridae viruses.

Frakolaki E., Niotis G., Karakostas C., Giannakopoulou E., Pardali V., Windisch M., Bartenschlager R., Papageorgiou N., Canard B., Zoidis G. and N. Vassilaki.

  • 31st International Conference on Antiviral Research (ICAR). Porto, Portugal, 11-15 June 2018

Αναρτημένη παρουσίαση: Acetohydroxamic Metal-Chelators against Hepatitis C Virus and Flaviviruses

Giannakopoulou E., Pardali V., Frakolaki E., Myrianthopoulos V., Mikros E., Bartenschlager R., Vassilaki N. and Zoidis G.

  • 23rd International Symposium on Hepatitis C Virus and Related Viruses. Kyoto, Japan, 11-15 Oct. 2016

Poster presentation: Broadly active antivirals with a naturally derived chelating moiety targeting hepaci- and flavivirus replication; further evaluation under liver normoxic conditions

Frakolaki E., Giannakopoulou E., Myrianthopoulos V., Dimitriou M., Madan V., Mikros E., Bartenschlager R., Mavromara P., Zoidis G. and Vassilaki N.

  • 29th International Conference on Antiviral Research (ICAR). La Jolla, California, United States, 17- 21 April 2016

Poster presentation: Novel indole-flutimide Heterocycles with Activity Against Influenza PA Endonuclease and Hepatitis C Virus

Zoidis G., Giannakopoulou E., Stevaert A., Frakolaki E., Myrianthopoulos V., Fytas G., Mavromara P., Mikros E., Bartenschlager R., Vassilaki N. and Naesens L.

  • 66th Panhellenic Conference of the Hellenic Society for Biochemistry and Molecular Biology. Eugenides Foundation, Athens, Greece, 11-13 Dec. 2015

Oral presentationDeveloping a novel infectious cell culture system of Hepatitis C virus that simulates liver normoxia for the characterization of broadly effective inhibitors targeting the viral polymerase.

Frakolaki E., Giannakopoulou E., Myrianthopoulos V., Dimitriou M., Madan V., Bartenschlager R., Mavromara P., Zoidis G. and Vassilaki N.

E. Investigating the role of the HCV core+1/ARFP (alternative reading frame) protein in viral pathogenesis. We and others have previously discovered the expression of an alternative open reading frame that overlaps the core encoding sequence at +1 nucleotide (core+1 ORF). Different core+1 ORF products, derived from frameshifting or internal translation initiation, have been reported. We study the mRNA/miRNA expression profile of human hepatoma cells and immortalized hepatocytes infected with core+1 mutant viruses of HCV JFH1 isolate (genotype 2a), carrying non-sense mutations that abolish the translation of the core+1 open reading frame, as compared to cells infected with wild-type virus, employing the technology of Real-Time PCR arrays of the Molecular Virology lab obtained through the program ARISTEIA (P.I. Prof. P. Mavromara).

F. Studying the role of an alternative IRES element embedded within the core coding sequence of HCV genome in modulating translation initiation of the core+1 open reading frame. Core RNA stem-loops SL47 and SL87 of the HCV genome, in addition to their role in the translation of viral polyprotein, are also important for driving the expression of the short isoform of the core+1 alternative reading frame protein, via internal translation initiation at core+1 codons 85/87, in hepatocytes transfected with core RNA as well as in the context of the viral genome.

PRESENTATIONS in CONFERENCES

  • 22nd International Symposium on Hepatitis C Virus and Related Viruses. Strasbourg, France, 9-13 Oct. 2015

Poster presentation: Expression and functional properties of the short Core+1/ARF protein in the HCV life cycle

Vassilaki N., Frakolaki E., Kazazi D., Karakasiliotis I., Moustafa S., Bartenschlager R. and Mavromara P.

  • 10th Conference of the Hellenic Society of Virology. Athens, Greece, 27-28 Feb. 2015

Oral presentationPhenotypic evaluation of mutations that disrupt the core+1 ORF or alter the core aminoacid sequence of Hepatitis C Virus

Vassilaki N., Frakolaki E., Samaras A., M. Dimitriou, Kotta-Loizou I., Karakasiliotis I., Bartenschlager R. and Mavromara P.

  • Scientific Symposium of the Institut Pasteur International Network 2014. Paris, 10-13 Sep. 2014
  • 21st International Symposium on Hepatitis C Virus and Related Viruses. Banff, Canada, 7-11 Sep. 2014

Poster presentation: Mutations introducing stop codons in HCV core+1 ORF and a single aminoacid substitution in core which is present in clinical isolates impair viral infectivity

Vassilaki N., Frakolaki E., Samaras A., Kotta-Loizou I., Karakasiliotis I., Bartenschlager R. and Mavromara P.

  • 64o Panhellenic Conference of the Hellenic Society for Biochemistry and Molecular Biology. Athens, Greece, 6-8 Δεκ. 2013

Oral presentation: An IRES-like element identified within the HCV core-coding region mediates internal translation initiation of the core+1/Short protein in the HCV replicon.

Vassilaki N., Kotta-Loizou I., Sakellariou P., Frakolaki E., Bartenschlager R. and Mavromara P.

Participation as a Coordinator:

International Pasteur Network grant for SARS-CoV-2 2020-2022:

Implication of dopamine, serotonin and hypoxia-inducible-factor pathways as determinant factors of SARS‐CoV-2 pathogenesis and COVID-19 severity: Towards therapeutic application (Acronym: DopaHypoCov).

Collaborators: IP Paris (Bioinformatics and Biostatistics HUB, CNRS – USR3756 – Department of Computational Biology – Dr C. Malabat, Dr P. Lechat, Dr A. Vaysse, and Unit Arbovirus and Insect Vectors, Department of Virology – Dr C. Dauga), PI in Ho Chi Minh City (Vietnam) (Directorial Board – Dr Q. C. Hoang) and Institut Pasteur du Maroc (Virology Unit, Viral Hepatitis Laboratory – S. Ezzikouri, S. Benjelloun and Medical Virology and BSL-3 Laboratory – J. Nourlil), HPI Department of Diagnostics (Dr E. Angelakis), NKUA Medical School, Evangelismos Hospital, First Department of Critical Care Medicine & Pulmonary Services, GP Livanos and M Simou Laboratories, (Dr A. Kotanidou. Dr A.G Vassiliou), NKUA, Faculty of Biology (Dr D. Vassilacopoulou)

Three-year Doctoral scholarship of Excellence 2020-2023, following an open call of the Hellenic Pasteur Institute, funded by Nostos Foundation, to the student George Mpekoulis, for the research proposal:

      Study of the interaction of Flaviviridae viruses with the signaling pathway of hypoxia and application in therapeutic approaches

IKY (State Scholarships Foundation) Postdoc Scholarship grant 2019-2021 (MIS 5033021):

L-dopa decarboxylase: An unexpected correlation with hepatitis B, hepatitis C and dengue virus infections and its application towards the discovery of new therapeutic strategies, for the postdoctoral researcher: Dr Efseveia Frakolaki

2019-2020       Asklepios Gilead Sciences Hellas grant 2018

Title: “Aromatic L-aminoacid decarboxylase: A new metabolic factor associated with Hepatitis C virus infection and the development of Hepatocellular Carcinoma”
Principal Investigator:  Dr N. Vassilaki
Collaborators: Dr D. Vassilacopoulou (Faculty of Biology, University of Athens, Greece), Prof. J. Koskinas (2nd Department of Internal Medicine of Athens University Medical School and Hippokration General Hospital) Prof. N. Pouli and P. Marakos (Faculty of Pharmacy, University of Athens, Greece), Dr H. Boleti (HPI, Light Mocroscopy Unit)

 2018-2019       Empeirikeion Foundation Research grant 2016 

Title: “Design, synthesis and biological characterization of novel broadly active inhibitors against Hepatitis C virus and the related re-emerging Flaviviruses Zika, Dengue and Yellow Fever. Validation in a cell-based infectious model simulating in vivo conditions of the tissue”

Principal Investigators: Dr N. Vassilaki (Molecular Virology Lab, Hellenic Pasteur Institute, Athens, Greece) and Prof. G. Zoidis (Faculty of Pharmacy, University of Athens, Greece).

Collaborators: Dr V. Myrianthopoulos (Faculty of Pharmacy, University of Athens, Greece), Prof. R. Bartenschlager (Department of Infectious Diseases, Heidelberg, Germany)

 

2017-2018       Asklepios Gilead Sciences Hellas grant 2016

Title: “Characterization of new synthetic and natural compounds with broad-spectrum anti-viral activity as inhibitors of Hepatitis B virus in a cell culture model simulating the in vivo normoxic microenvironment. Importance of liver normoxia for HBV replication and the efficiency of inhibitors”

Principal Investigator: Dr N. Vassilaki

Collaborators: Prof. A. L. Skaltsounis, Prof. G. Zoidis and Dr V. Myrianthopoulos (Faculty of Pharmacy, University of Athens, Greece), Dr C. Neuveut (IP Paris, Unité des Hépacivirus et Immunité Innée), Dr M. Windisch (IP Korea, Applied Molecular Virology).

2017-2019       IKY (State Scholarships Foundation) Doctoral Grant for the research project “Evaluation of novel inhibitors of Hepatitis C and related viruses and biomarkers of response to anti-viral therapeutics”,

Thesis project of the PhD student Efseveia Frakolaki
IKY and the European Social Fund (ESF) and the Public Investments Program, in the framework of the Operational Program “Education and Life Long Learning” within the National Strategic Reference Framework (NSRF) 2007-2013

Principal Investigator: Niki Vassilaki/ IKY and the European Social Fund (ESF) and the Public Investments Program, in the framework of the Operational Program “Education and Life Long Learning” within the National Strategic Reference Framework (NSRF) 2007-2013

Jan-May 2018       Erasmus+ EU funding for traineeship of the Biologist Giorgos Niotis in the laboratory Architecture et Fonctions des Macromolécules Biologiques (AFMB), UMR 7257 du CNRS et de l’Université Aix-Marseille (France), in the context of the research project “Lipophilic heterocyclic chelating agents (acetohydroxamic acids) that are broadly active against Flaviviridae viruses. Evaluation in enzymatic assays for viral metallo-enzymes from Flaviviruses and Arenaviruses; Co-relation with inhibitory activities determined in sub-genomic replicon transfected cells”

Principal Investigator: Niki Vassilaki (Molecular Virology, HPI) and Bruno Canard – Prof. Nicolas Papageorgiou (AFMB, UMR 7257 du CNRS et de l’Université Aix-Marseille, France)

2018-2019       Subproject of action Development grants for research institutions – KRIPIS IΙ (Greek General Secretariat for Research and Technology)

Program Title: “Infectious, autoimmune and neurodegenerative diseases: Study of pathogenetic mechanisms and development of diagnostic, prognostic and therapeutic approaches”.

Coordinator:  Dr E. Karagouni (Hellenic Pasteur Institute)

Subproject EE1.5: “Identification of broadly effective inhibitors against Flaviviridae viruses and Hepatitis B virus (HBV)”

Principal Investigator of subproject EE1.5: Dr N. Vassilaki

2019-2021       Subproject of the action ESFRI- European Strategy Forum for Research Infrastructures, National Research & Innovation Infrastructures EATRIS-GRInfrastructure for Preclinical and Early-Phase Clinical Development of Drugs, Therapeutics and BioMedical Devices.

Coordinator: Paschalis Sideras (Biomedical Research Foundation Academy of Athens)

Title of subproject: “Application of advanced in vitro viral models for the preclinical evaluation of small molecule inhibitors and other drugs against Flaviviruses (Dengue, Yellow Fever, Zika)”

Principal Investigator of subproject: Dr N. Vassilaki

2018-2020       Participation in Single RTDI State Aid Action RESEARCH – CREATE – INNOVATE (EPAnEK, Greek General Secretariat for Research and Technology): “Development of peptide-based nanovaccines against Leishmanasis (NanoVacLeish)”.

Principal Investigator: Dr E. Karagouni

Participants:  Hellenic Pasteur Institute (Coordinator), Centre for Research and Technology Hellas, Gerolymatos International S.A.

2015-2017:      International Pasteur Network grant ACIP (Actions Concertées Inter-Pasteuriennes) 2015

Title: “Identification of broad-spectrum naturally derived inhibitors against hepatotropic viruses (DENV, YFV, HBV) under culture conditions simulating liver normoxic and metabolic microenvironment. The interplay between virus and hepatic normoxia as a possible disease determinant”.

Principal Investigator/Coordinator: Dr N. Vassilaki

Collaborating Institut Pasteur (IP) Network partners: C. Neuveut (IP Paris, Unité des Hépacivirus et Immunité Innée), M. Windisch (IP Korea, Applied Molecular Virology). Other collaborators: Prof. R. Bartenschlager (Department of Infectious Diseases, University of Heidelberg, Germany), Prof. A. L. Skaltsounis, Prof. Zoidis and Dr V. Myrianthopoulos (Faculty of Pharmacy, University of Athens, Greece)

2017                Subproject of Asklepios Gilead Sciences Hellas grant 2017

Program title: “Design, synthesis and biological evaluation of new bivalent inhibitors of NS5A with selective anti-HCV activity”.

Coordinator: Prof. G. Zoidis, Faculty of Pharmacy, University of Athens

Principal Investigator of the biological evaluation of the inhibitors against HCV: Dr N. Vassilaki

2016-2017       Subproject of Asklepios Gilead Sciences Hellas program 2015 concerning the evaluation against HCV of novel lipophilic heterocyclic chelating agents

Program title: “Design, synthesis and biological evaluation of novel lipophilic heterocyclic chelating agents against Hepatitis C virus”

Coordinator: Prof. G. Zoidis, Faculty of Pharmacy, University of Athens

Principal Investigator of the study on HCV: Dr N. Vassilaki

2013-2014       LATSIS Public Benefit Foundation grant:

Title: ‘Development and exploitation of a more true-to-life novel infectious cell culture system for HCV growth for the characterization of new anti-HCV drugs’.

Principal Investigator/Coordinator: Dr N. Vassilaki

National collaborations: Prof. P. Mavromara (Democritus University of Thrace, Hellenic Pasteur Institute), Prof. J. Koskinas (2nd Department of Internal Medicine, Medical School of Athens, Hippokration Hospital, Athens), Prof. A. L. Skaltsounis, Prof. N. Aligiannis and Dr A. Argyropoulou (Faculty of Pharmacy, University of Athens, Department of Pharmacognosy and Chemistry of Natural Compounds), Prof. G. Zoidis (Faculty of Pharmacy, University of Athens, Department of Pharmaceutical Chemistry), Prof. M. Hatzopoulou-Cladaras and Dr I. Vallianou (School of Biology, Aristotle University of Thessaloniki, Department of Genetics, Development and Molecular Biology)

International collaboration: Prof. R. Bartenschlager (Department of Infectious Diseases, Heidelberg University, Germany)

2013-2015:      Subprojects of action Development grants for research institutions – KRIPIS I (Greek General Secretariat for Research and Technology)

Program title: “Infectious and neurodegenerative diseases in the 21st century: From the study of basic mechanisms to the development of translational research and cutting-edge methodologies targeting diagnosis, prevention and treatment”.

Coordinator: Dr E. Karagouni (Hellenic Pasteur Institute)

Subproject EE2.2: “Development and exploitation of a more true-to-life novel infectious cell culture system for HCV growth”. Subproject EE4.2: “Role of circulating microRNAs as prognostic biomarkers for HCV-associated hepatocellular carcinoma’.

Principal Investigator of subprojects EE2.2 and EE4.2: Dr N. Vassilaki

2013-2015       Subproject of National Grant BIONIAN, Greek Life Sciences Cluster (Greek General Secretariat for Research and Technology), where H.P.I. has participated as a subcontractor of the company Institute for Clinical Investigation

Subproject title: “Novel inhibitors of HCV growth and biomarkers related to HCV pathogenesis and response to therapeutics. A) A set of novel inhibitors of Hepatitis C Virus growth. B) Evaluation of microRNAs as biomarkers for HCV pathogenesis and response to anti-virals”. Principal Investigator of subproject: Dr N. Vassilaki

2013-2015       Subproject of program ARISTEIA Oncohepcvir (Greek General Secretariat for Research and Technology)

Program title: “The role of oncogenic viruses in the pathogenesis of hepatocellular carcinoma: From the HCV core/core+1 protein/ host interactions to HCV-associated liver cancer”.

Principal Investigator: Prof. P. Mavromara (Hellenic Pasteur Institute)

Subproject title: Investigating the role of HCV core+1/ARFP/F protein in viral pathogenesis by analyzing the mRNA/miRNA profiles of hepatocytes supporting the replication of wild-type of core+1 mutant viruses (carrying non-sense mutations abolishing the translation of core+1 open reading frame)

Principal Investigator of subproject: Dr N. Vassilaki

2013-2015       Participation in program THALΕS (Ministry of Education)

Program title: STAGECAR “Μechanisms of signal transduction and gene expression in hepatocellular carcinoma”.

Coordinator: Prof. G. Mosialos, Collaborators: Prof. M. Hatzopoulou-Cladaras and Dr I. Vallianou (School of Biology, Aristotle University of Thessaloniki, Department of Genetics, Development and Molecular Biology).

Study title: Hepatitis C virus suppresses HNF4alpha, a key regulator of hepatocellular carcinogenesis

2006-2007       DAAD, German Academic Exchange Post-doctoral Research grant:

Title“Role of hepatitis C virus core+1 open reading frame and core cis-acting RNA elements in hepatitis C virus life cycle”

The post-doctoral research of Dr N. Vassilaki was performed at the Department of Molecular Virology of Heidelberg University (Germany), which is headed by Prof. Ralf Bartenschlager, in collaboration with the Molecular Virology lab of H.P.I.

Participation as a Principal Investigator of Subprojects:

Subproject of action ESFRI- European Strategy Forum for Research Infrastructures, National Research & Innovation Infrastructures EATRIS-GR Jan. 2019 – Dec. 2022 (MIS 5028091): Infrastructure for Preclinical and Early-Phase Clinical Development of Drugs, Therapeutics and BioMedical Devices. Subproject: Application of advanced in vitro viral models for the preclinical evaluation of small molecule inhibitors and other drugs against Flaviviruses (Dengue, Yellow Fever, Zika). Coordinator: Dr P. Sideras (Biomedical Research Foundation Academy of Athens), Dr Karagouni E. Member of the coordinating committee. Other partners: NIR, University of Trace, University of Patras, and FRT. Principal Investigator of subproject: Dr N. Vassilaki

Subproject of action KRIPIS II: Development grants for research institutions Oct. 2017 – Sept. 2019 (MIS5002486), under the «Action Strategic Development on the Research and Technological Sector» funded by the Operational Program «Competitiveness, Entrepreneurship and Innovation» (NSFR 2014-2020), and co-financed by the Greek State and the European Regional Development Fund: Infectious, autoimmune and neurodegenerative diseases: study of pathogenic mechanisms and development of diagnostic/prognostic/therapeutic strategies. Subproject: Broadly active inhibitors against Flaviviridae viruses and HBV. Coordinator: Dr E. Karagouni (Hellenic Pasteur Institute). Principal Investigator of subproject: Dr N. Vassilaki

2016-2017            Subproject of Asklepios Gilead Sciences Hellas program 2015

Design, synthesis and biological evaluation of novel lipophilic heterocyclic chelating agents against Hepatitis C virus

Coordinator: Prof. G. Zoidis, Faculty of Pharmacy, University of Athens

Principal Investigator of the biological evaluation of the chelating agents against HCV: Dr N. Vassilaki

2013-2015:          Subprojects of action Development grants for research institutions – KRIPIS I (Greek General Secretariat for Research and Technology)

Program title: “Infectious and neurodegenerative diseases in the 21st century: From the study of basic mechanisms to the development of translational research and cutting-edge methodologies targeting diagnosis, prevention and treatment”.

Coordinator: Dr E. Karagouni (Hellenic Pasteur Institute)

Subproject EE2.2: “Development and exploitation of a more true-to-life novel infectious cell culture system for HCV growth”. Subproject EE4.2: “Role of circulating microRNAs as prognostic biomarkers for HCV-associated hepatocellular carcinoma’.

Principal Investigator of subprojects EE2.2 and EE4.2: Dr N. Vassilaki

2013-2015            Subproject of National Grant BIONIAN, Greek Life Sciences Cluster (Greek General Secretariat for Research and Technology), where H.P.I. has participated as a subcontractor of the company Institute for Clinical Investigation

Subproject title: “Novel inhibitors of HCV growth and biomarkers related to HCV pathogenesis and response to therapeutics. A) A set of novel inhibitors of Hepatitis C Virus growth. B) Evaluation of microRNAs as biomarkers for HCV pathogenesis and response to anti-virals”. Principal Investigator of subproject: Dr N. Vassilaki

2013-2015            Subproject of program ARISTEIA Oncohepcvir (Greek General Secretariat for Research and Technology)

Program title: “The role of oncogenic viruses in the pathogenesis of hepatocellular carcinoma: From the HCV core/core+1 protein/ host interactions to HCV-associated liver cancer”.

Principal Investigator: Prof. P. Mavromara (Hellenic Pasteur Institute)

Subproject title: Investigating the role of HCV core+1/ARFP/F protein in viral pathogenesis by analyzing the mRNA/miRNA profiles of hepatocytes supporting the replication of wild-type of core+1 mutant viruses (carrying non-sense mutations abolishing the translation of core+1 open reading frame)

Principal Investigator of subproject: Dr N. Vassilaki

Participation as a Partner:

EU Recovery fund – Ministry of Development and Investments grant: Participation in the design and writing of the approved proposal submitted from the Hellenic Pasteur Institute for the Creation of a Pathogens Research Centre (HPI-PRC), Center of Excellence for enhancing Research, Surveillance and Prevention of Emerging and Re-emerging diseases

High Technology Infrastructure for Preclinical Studies and Provision of Specialized Services for Infectious and Neurodegenerative Diseases July 2021 – Dec. 2023 (MIS 5066768), implemented under the Priority Axis «Strengthening the Mechanisms and Investments of SMEs of the Attica Region in Research and Innovation» funded by the Operational Program «Attiki 2014-2020» (NSFR 2014-2020), and co-financed by the Greek State and the European Regional Development Fund.

Single RTDI State Aid Action RESEARCH – CREATE – INNOVATE 20182021 NanoVacLeish (MIS5031816) /EPAnEK, GSRT: Development of peptide-based nanovaccines against Leishmanasis. Principal Investigator: Dr E. Karagouni, Hellenic Pasteur Institute (Coordinator), CERTH, Gerolymatos International S.A.

Asklepios Gilead Sciences Hellas grant 2018-2019Design, synthesis and biological evaluation of new bivalent inhibitors of NS5A with selective anti-HCV activity. Coordinator: Prof. G. Zoidis, Faculty of Pharmacy, University of Athens

2013-2015            Participation in program THALΕS (Ministry of Education)

Program title: STAGECAR “Μechanisms of signal transduction and gene expression in hepatocellular carcinoma”.

Coordinator: Prof. G. Mosialos, Collaborators: Prof. M. Hatzopoulou-Cladaras and Dr I. Vallianou (School of Biology, Aristotle University of Thessaloniki, Department of Genetics, Development and Molecular Biology).

Study title: Hepatitis C virus suppresses HNF4alpha, a key regulator of hepatocellular carcinogenesis

PhD theses

Evaluation of novel inhibitors of Hepatitis C virus and biomarkers of response to anti-viral therapeutics“, Efseveia Frakolaki, PhD thesis 2014-2019, Faculty of Biology, University of Athens, Department of Genetics and Biotechnology, 3-member advisory committee: Prof. A. M. Pappas, Dr N. Vassilaki, Prof. P. Mavromara. Awarded by IKY (State Scholarships Foundation) Doctorate Scholarship grant, co-financed by Greece and the European Union (European Social Fund-ESF) through the Operational Programme “Human Resources Development, Education and Lifelong Learning 2014- 2020”

Study of the interaction of Flaviviridae family viruses with the hypoxia signaling pathway and application in therapeutic approaches“, Georgios Mprekoulis, PhD thesis 2020 – current, Faculty of Biology, University of Athens, Department of Biochemistry and Molecular Biology, 3-member advisory committee: Dr. D. Vassilacopoulou, Dr N. Vassilaki, Dr D. Siredis. Awarded by an Excellence PhD fellowship of Hellenic Pasteur Institute funded from Nostos Foundation

 

MSc Diploma theses

Studying cellular energetic metabolism and viral replication in cultured cells infected with Flaviviridae viruses under conditions of liver normoxia and in relation to L-Dopa decarboxylase“, Panagiota Kaimou, Master thesis 2018, Faculty of Biology, University of Athens, Department of Biochemistry and Molecular Biology, Postgraduate studies program Clinical Biochemistry – Molecular Diagnostics (Molecular Basis of Human Diseases)

Molecular mechanisms determining the relationship among viral infection, tissue normoxia and L-Dopa decarboxylase for hepatotropic viruses“, Maria Moraiti, Master thesis 2019, Faculty of Biology, University of Athens, Department of Biochemistry and Molecular Biology, Postgraduate studies program Clinical Biochemistry – Molecular Diagnostics (Molecular Basis of Human Diseases)

The importance of L-Dopa decarboxylase as a metabolic determinant of viral replication and pathogenesis“, Anna Chalari, Master thesis 2020, Faculty of Biology, University of Athens, Department of Biochemistry and Molecular Biology, Postgraduate studies program Clinical Biochemistry – Molecular Diagnostics (Molecular Basis of Human Diseases)

Interaction of the Flaviviridae viruses life cycle with host cell factors, including L-Dopa decarboxylase and novel therapeutic approaches“, Vasilina Tsopela, Master thesis 2019 – current, Faculty of Biology, University of Athens, Department of Biochemistry and Molecular Biology, Postgraduate studies program Clinical Biochemistry – Molecular Diagnostics (Molecular Basis of Human Diseases)

 

Undergraduate diploma theses

Characterizing the biological function of the Hepatitis C virus core/core+1 protein Panagiotis Sakellariou, Diploma thesis 2013, Faculty of Biology, University of Athens, Department of Biochemistry and Molecular Biology

Evaluating novel inhibitors of Hepatitis C virus proliferation” Marios Dimitriou, Diploma thesis 2015, Faculty of Biology, University of Athens, Department of Biochemistry and Molecular Biology

Study of natural and semisynthetic compounds for their inhibitory activity against the proliferation of Hepatitis C Virus and related Flaviviruses” Konstantinos Kelepouras, Diploma thesis 2017, Faculty of Biology, University of Athens, Department of Biochemistry and Molecular Biology

 

Evaluating broadly active inhibitors of viral replication and characterizing their mechanism of action at the genetic level through the study of adaptive changes in the virus genome and the host cell“, Christos Caracostas, Diploma thesis 2019, Faculty of Biology, University of Athens, Department of Genetics and Biotechnology

Study of the interaction between viral replication and cellular metabolism under conditions of tissue normoxia (low oxygen) and in relation to L-Dopa decarboxylase“, Nikolaos Kolaitis, Diploma thesis 2019, Faculty of Biology, University of Athens, Department of Biochemistry and Molecular Biology

Association between hepatotropic viruses and tissue normoxia: studying the implicated cellular factors, including L-Dopa decarboxylase, and the impact on the efficiency of anti-virals“, Vasileios Siozos, Diploma thesis 2020, Faculty of Biology, University of Athens, Department of Biochemistry and Molecular Biology

Effect of Flaviviridae viruses life cycle on human cell proteins, such as RΝase K, and identification of novel inhibitors of flaviviral replication“, Giorgos Panos, Diploma thesis 2019 – current, Faculty of Biology, University of Athens, Department of Biochemistry and Molecular Biology

Role of L-Dopa decarboxylase and functionally associated factors in the life cycles of Flaviviridae viruses, and the identification of novel modifiers of flaviviral replication, using viral particles produced with in vitro assays“, Raphaela Milona, Diploma thesis 2020 – current, Faculty of Biology, University of Athens, Department of Biochemistry and Molecular Biology

Studying the action of viral replication inhibitors, such as enzymatic products and modulators of the activity of the dopamine biosynthetic pathway“, Despoina Lagou, Diploma thesis 2021 – current, Faculty of Biology, University of Athens, Department of Biochemistry and Molecular Biology

 

Internships on the study of the anti-viral activity of rationally-designed synthetic inhibitors targeting the replication of Flaviviridae and HBV viruses as well as on the study of the association of HCV life cycle with the catecholamine biosynthetic/metabolic pathway in hepatocytes (2 Internships of Postgraduate students Maria Gerasi, Erofili Giannakopoulou and 2 Internships of Undergraduate students Christos Petritsis, Constantinos Sideris)

Mentoring of 3 Post-Doctoral fellows: Dr Katerina Kalliampakou (“Identification of broadly effective inhibitors against viruses of Flaviviridae family and Hepatitis B virus“), Dr Efseveia Frakolaki (“Evaluation of novel inhibitors of Hepatitis C and related viruses and biomarkers of response to anti-viral therapeutics“), Dr Vallianou Ioanna (“Studying the interaction between Hepatitis C virus and Hepatocyte Nuclear Factor 4 alpha, a key regulator of hepatocellular carcinoma“)

 

Teaching in Postgraduate studies programs

2018-2022: Participation in the Lectures “Molecular basis of viral diseases and their treatment”, Inter-University Postgraduate studies program CLINICAL BIOCHEMISTRY – MOLECULAR DIAGNOSTICS, in the context of the course Molecular Basis of Human Diseases, Faculty of Biology, University of Athens. Evaluation of seminars in the subject of the course.

2018-2019Lectures “Viruses as tools for vaccine construction, diagnosis and drug discovery”, Postgraduate studies program MICROBIAL BIOTECHNOLOGY, Faculty of Biology, University of Athens

Reviewer in the international journals ‘Journal of General Virology’, ‘Virus Research’, ‘Biochimie’, ‘International Journal of Molecular Sciences’, ‘International Journal of Environmental Research and Public Health’ and ‘IUBMB Life’.

2018               Invited Co-Chair at the 25th International Symposium on Hepatitis C Virus and Related Viruses (HCV2018, Dublin, Ireland). Session: Emerging and Related Viruses

2018                Best Oral Presentation Award, 4th Meeting of Postgraduate and Postdoctoral Researchers of Hellenic Pasteur Institute. “Interaction between tissue normoxia and Dengue Virus replication“. Moraiti M., Frakolaki E., Kolaitis N., Kaimou P., Kalliampakou A., Karampetsou K., Dotsika E., Vassilacopoulou D., Mavromara P., Bartenschlager R. and Vassilaki N.

2016     The article “Novel indole-flutimide heterocycles with activity against influenza PA endonuclease and hepatitis C virus”, in Med. Chem. Comm. 2016, Vol.7, No3, p.447-456, of Zoidis G., Giannakopoulou E., Stevaert A., Frakolaki E., Myrianthopoulos V., Fytas G., Mavromara P., Mikros E., Bartenschlager R., Vassilaki Ν. and Naesens L., was featured as: a) New Talent Europe, b) 2016 MedChemComm Hot Article and c) Front cover

2016     International Pasteur Network traineeship grant Calmette & yersin 2016 awarded for training of the PhD student E. Frakolaki in Institut Pasteur Paris on the research topic: “Evaluation of broadly active anti-virals for their activity against Hepatitis B Virus in a cell culture model adapted at liver normoxic conditions”.

2016     Two awards for best trainees’ performance during the course ‘High Content Assay for Drug Screening and Target discovery Using RNAi Technology’ (Institut Pasteur Korea, 9-13 May)

2012     Poster presentation award from the 63rd Conference of the Hellenic Society for Biochemistry and Molecular Biology (HSBMB) 2012 for the study: “Low Oxygen Tension Enhances Hepatitis C Virus Replication”, of Vassilaki N., Kalliampakou K.I., Kotta-Loizou I., Befani C., Liakos P., Simos G., Mentis A.F., Kalliaropoulos A., Doumba P.P., Smirlis D., Bauhofer O., Poenisch M., Windisch M.P., Lee M.E., Koskinas J., Bartenschlager R. and Mavromara P.

2011     Federation of European Microbiological Societies (FEMS) Young Scientist Meeting Grant 2010 for oral presentation at the 4th European Congress of Virology (Cernobbio, Italy, 7-11 Apr. 2010): “Oxygen tension modulates hepatitis C virus proliferation”, of Vassilaki N., Kalliampakou K.I., Kotta-Loizou I., Smirlis D., Bartenschlager R. and Mavromara P.

2008     Federation of European Microbiological Societies (FEMS) Young Scientist Meeting Grant 2008 for presentation at the 14th International Congress of Virology of International Union of Microbiological Societies (Istanbul, Turkey, 10-15 Aug. 2008): “Exploring the importance of the hepatitis C virus core RNA secondary structure and core+1 reading frame expression for viral RNA translation and replication”, of Vassilaki N., Friebe P., Paranhos-Baccalà G., Mavromara P. and Bartenschlager R.

 

ΤΕCHNOLOGY

  Real-Time PCR Array technology of the Molecular Virology lab at H.P.I. is available to scientists of H.P.I. and other Research Institutes/ Universities and integrates standard real-time PCR applications like nucleic acid quantification, detection of single nucleotide polymorphisms (SNPs), and copy number variation detection with others that include high-resolution melting (HRM), protein analysis with proximity ligation technology (Taqman protein assays), and gene expression analysis performed directly from cultured cells without RNA purification.

 

Responsible contact person: Niki Vassilaki (Image removed.@Image removed.)

Mavromara P. and Vassilaki N. “Novel HCV core+1 protein, methods for diagnosis of HCV infections, prophylaxis and for screening of anti-HCV agents, nucleic acids and new polypeptides associated with and/or overlapping with HCV core gene products”
U.S. Patent Office, Patent No. US 7,838,002 B2, Application No. 11/322,374, Issue date 23/11/2010

Mavromara P. and Vassilaki N. “In vitro expression of the HCV ARFP/F/CORE+1 coding open reading frame”
U.S. Provisional Patent Application No. 60/614,610

2022

Dengue Virus Replication Is Associated with Catecholamine Biosynthesis and Metabolism in Hepatocytes. Mpekoulis G, Tsopela V, Chalari A, Kalliampakou KI, Panos G, Frakolaki E, Milona RS, Sideris DC, Vassilacopoulou D, Vassilaki N.* (2022) Viruses 9;14(3):564. doi: 10.3390/v14030564. * Corresponding author

Characterizing Kinetics and Avidity of SARS-CoV-2 Antibody Responses in COVID-19 Greek Patients. Labropoulou S.†, Vassilaki N.*†, Milona R.S., Terpos E., Politou M., Pappa V., Pagoni M., Grouzi E., Dimopoulos M.A., Mentis A., Emmanouil M. and Angelakis E. (2022) Viruses 14(4), 758; doi: 10.3390/v14040758. * Corresponding author, † Equal co-first authors

Redesigning of the cap conformation and symmetry of the diphenylethyne core to yield highly potent pan-genotypic NS5A inhibitors with high potency and high resistance barrier. Abdallah M, Hamed MM, Frakolaki E, Katsamakas S, Vassilaki N, Bartenschlager R, Zoidis G, Hirsch AKH, Abdel-Halim M, Abadi AH. (2022) Eur J Med Chem. 5;229:114034. doi: 10.1016/j.ejmech.2021.114034.

2021

Association of Hepatitis C Virus Replication with the Catecholamine Biosynthetic Pathway. Mpekoulis G, Tsopela V, Panos G, Siozos V, Kalliampakou K. I., Frakolaki E, Sideris C, D, Vassiliou A.G, Sideris D.C., Vassilacopoulou Dido and Vassilaki N*. Viruses 2021, 13(11), 2139; https://doi.org/10.3390/v13112139 * Corresponding author

Alteration of L-Dopa decarboxylase expression in SARS-CoV-2 infection and its association with the interferon-inducible ACE2 isoform. Mpekoulis G, Frakolaki E, Taka S, Ioannidis A, Vassiliou AG, Kalliampakou KI, Patas K, Karakasiliotis I, Aidinis V, Chatzipanagiotou S, Angelakis E, Vassilacopoulou D, Vassilaki N.* PLoS One. 2021, 29;16(6):e0253458. doi: 10.1371/journal.pone.0253458. * Corresponding author

Impact of Age and Sex on Antibody Response Following the Second Dose of COVID-19 BNT162b2 mRNA Vaccine in Greek Healthcare Workers. Vassilaki N, Gargalionis AN, Bletsa A, Papamichalopoulos N, Kontou E, Gkika M, Patas K, Theodoridis D, Manolis I, Ioannidis A, Milona RS, Tsirogianni A, Angelakis E, Chatzipanagiotou S. Microorganisms. 2021, 9(8):1725. doi: 10.3390/microorganisms9081725.

Increased Autotaxin Levels in Severe COVID-19, Correlating with IL-6 Levels, Endothelial Dysfunction Biomarkers, and Impaired Functions of Dendritic Cells. Nikitopoulou I, Fanidis D, Ntatsoulis K, Moulos P, Mpekoulis G, Evangelidou M, Vassiliou AG, Dimakopoulou V, Jahaj E, Tsipilis S, Orfanos SE, Dimopoulou I, Angelakis E, Akinosoglou K, Vassilaki N, Tzouvelekis A, Kotanidou A, Aidinis V. Int J Mol Sci. 2021, 22(18):10006. doi: 10.3390/ijms221810006.

Design and Synthesis of Novel Symmetric Fluorene-2,7-diamine Derivatives As Potent Hepatitis C Virus Inhibitors. Mousa M. H. A., Ahmed N. S., Schwedtmann K., Frakolaki E., Vassilaki N., Zoidis G., Weigand J. J., Abadi A. Pharmaceuticals, 2021, 14(4), 292; https:/doi.org/10.3390/ph14040292

2020

A Novel Cis-Acting RNA Structural Element Embedded in the Core Coding Region of the Hepatitis C Virus Genome Directs Internal Translation Initiation of the Overlapping Core+1 ORF. Vassilaki N.*, Frakolaki E., Kalliampakou K.I., Sakellariou P., Kotta-Loizou I., Bartenschlager R. and Mavromara P.* Int J Mol Sci. 2020, 21(18), 6974. doi: 10.3390/ijms21186974. * Corresponding authors

Design, synthesis and anti-HBV activity evaluation of new substituted imidazo[4,5-b]pyridines. Gerasi M.1, Frakolaki E.1, Papadakis G., Chalari A. Lougiakis N., Marakos, Pouli N.* and Vassilaki N.* Bioorg Chem. 2020, 103580. doi: 10.1016/j.bioorg.2020.103580. * Corresponding authors

Human L-Dopa decarboxylase interaction with Annexin V and expression during apoptosis. Chalatsa I., Arvanitis N., Arvanitis D., Tsakou A. C., Kalantzis E. D., Vassiliou A. G., Sideris D.C., Frakolaki E., Vassilaki N. and Vassilacopoulou D. Biochimie, 2020, 177, 78-86. doi: 10.1016/j.biochi.2020.08.010.

Symmetric benzidine derivatives as anti-HCV agents: insight into the nature, stereochemistry of the capping amino acid and the size of the terminal capping carbamates. Abdel Karim S. E., Youssef Y. H., Abdel-Halim M., Frakolaki E., Vassilaki N., Zoidis G., Ahmed N.S and Abadi A.H. Bioorg Chem. 2020, 102, 104089. doi: 10.1016/j.bioorg.2020.104089.

2019

Emerging role of L-Dopa decarboxylase in Flaviviridae virus infections. Frakolaki E., Kalliampakou K. I., Kaimou P., Moraiti M., Kolaitis N., Boleti H., Koskinas J., Vassilacopoulou D. and Vassilaki N.* Cells 2019, 8(8), pii: E837. doi: 10.3390/cells8080837. * Corresponding author

Scaffold Hybridization Strategy towards potent hydroxamate-based inhibitors of Flaviviridae viruses and Trypanosoma species. Giannakopoulou E., Pardali V., Frakolaki E., Siozos V., Myrianthopoulos V., Mikros E., Taylor M. C., Kelly J. M.*, Vassilaki N.* and Zoidis G.* MedChemComm 2019, 10(6):991-1006. doi: 10.1039/C9MD00200F. * Principal investigators

Symmetric Anti-HCV Agents: Synthesis, Antiviral Properties, and Conformational Aspects of Core Scaffolds. Leila A., Mousa M., Frakolaki E., Vassilaki N., Bartenschlager R., Zoidis G., Abdel-Halim M. and Abadi A.H. ACS Omega 2019, 4(7):11440-11454. doi: 10.1021/acsomega.9b01242.

L-Dopa decarboxylase interaction with the major signaling regulator ΡΙ3Κ in tissues and cells of neural and peripheral origin. Vassiliou A.G., Siaterli M.Z., Frakolaki E., Gkogkosi P., Paspaltsis I., Sklaviadis T., Vassilacopoulou D.* and Vassilaki N.* Biochimie. 2019, 160:76-87. doi: 10.1016/j.biochi.2019.02.009. * Corresponding authors

Comparison of DCs activation by virus-based vaccine delivery vectors emphasises the transcriptional downregulation of the oxidative phosphorylation pathway. Tsitoura E., Kazazi D., Oz-Arslan D., Sever E. A., Khalili S., Vassilaki N., Aslanoglou E., Dérian N, Six A., Sezerman O. U., Klatzmann D. and Mavromara P. Hum Gene Ther. 2019, 30(4):429-445. doi: 10.1089/hum.2018.161.

2018

The Role of Tissue Oxygen Tension in Dengue Virus Replication. Frakolaki E., Kaimou P., Moraiti M., Kalliampakou K. I., Karampetsou K., Dotsika E. Liakos P., Vassilacopoulou D., Mavromara P., Bartenschlager R. and Vassilaki N.* Cells. 2018, 7(12), pii: E241. Special Issue Gene Regulation by HIFs during Hypoxia. doi: 10.3390/cells7120241. * Corresponding author

Expanding the chemical space of anti-HCV NS5A inhibitors by stereochemical exchange and peptidomimetic approaches. Ramsis T.M., Abdel Karim S.E., Vassilaki N., Frakolaki E., Kamal A.A.M., Zoidis G., Ahmed N.S. and Abadi A.H. Arch Pharm (Weinheim). 2018, 351(7):e1800017. doi: 10.1002/ardp.201800017.

2017

Novel nucleoside analogues targeting HCV replication through an NS5A-dependent inhibition mechanism. Lougiakis N., Frakolaki E., Karmou P., Pouli N.*, Marakos P., Madan V., Bartenschlager R., Vassilaki N.* Chem Biol Drug Des. 2017, doi: 10.1111/cbdd.12966 * Corresponding authors

Virus-host interactions under hypoxia. Special issue: Effects of hypoxia on infection and host immune control. Vassilaki N.* and Frakolaki E. Microbes Infect. 2017, 19, 193-203. doi: 10.1016/j.micinf.2016.10.004. * Corresponding author

2016

# Novel indole-flutimide heterocycles with activity against influenza PA endonuclease and hepatitis C virus. Zoidis G., Giannakopoulou E., Stevaert A., Frakolaki E., Myrianthopoulos V., Fytas G., Mavromara P., Mikros E., Bartenschlager R., Vassilaki Ν.* and Naesens L.* Med. Chem. Comm. 2016, 7, 447-456. doi: 10.1039/C5MD00439J. * Principal investigators

# Featured as: New Talent Europe (top research from emerging investigators from Europe), 2016 MedChemComm Hot Article (particularly interesting or significant research), Front cover in MedChemComm

Hepatitis C virus suppresses Hepatocyte Nuclear Factor 4 alpha, a key regulator of hepatocellular carcinoma. Vallianou I., Dafou D., Vassilaki N., Mavromara P. and Hadzopoulou-Cladaras M. Int J Biochem Cell Biol. 2016, 78, 315-26. doi: 10.1016/j.biocel.2016.07.027.

2015

Expression of the novel HCV core+1/ARF protein in the context of JFH1-based replicons. Kotta-Loizou I., Karakasiliotis I., Vassilaki N., Sakellariou P., Bartenschlager R. and Mavromara P. J Virol. 2015, 89:5164-70. doi: 10.1128/JVI.02351-14.

2014

Viral Hepatitis. Robotis J.F.* and Vassilaki N.* In Reference Module in Biomedical Sciences, 2014, edited by M. Caplan, Elsevier. doi: 10.1016/B978-0-12-801238-3.05401-5. * Corresponding authors

2013

Low oxygen tension enhances hepatitis C virus replication. Vassilaki N.*, Kalliampakou K.I., Kotta-Loizou I., Befani C., Liakos P., Simos G., Mentis A.F., Kalliaropoulos A., Doumba P.P., Smirlis D., Foka P., Bauhofer O., Poenisch M., Windisch M.P., Lee M.E., Koskinas J., Bartenschlager R. and Mavromara P.* J Virol. 2013, 87, 2935-48. doi: 10.1128/JVI.02534-12. * Corresponding authors

Hepatitis C virus core+1/ARF protein decreases hepcidin transcription through an AP1 binding site. Kotta-Loizou I., Vassilaki N.*, Pissas G., Kakkanas A., Bakiri L., Bartenschlager R. and Mavromara P.* J Gen Virol. 2013, 94, 1528-34. doi: 10.1099/vir.0.050328-0 * Corresponding authors

High Levels of HCV core+1 Antibodies in HCV Patients with Hepatocellular Carcinoma. Dalagiorgou G., Vassilaki N., Foka P., Boumlic A., Kakkanas A., Kochlios E., Khalili S., Aslanoglou E., Veletza S., Orfanoudakis G., Vassilopoulos D., Hadziyannis S., Koskinas J., Mavromara P. J Gen Virol. 2011, 92: 1343-51. doi: 10.1099/vir.0.023010-0.

Synonymous mutations in the core gene are linked to unusual serological profile in hepatitis C virus infection. Budkowska A., Kakkanas A., Nerrienet E., Kalinina O., Maillard P., Horm S.V., Dalagiorgou G., Vassilaki N., Georgopoulou U., Martinot M., Sall A.Α., and Mavromara P. PLoS One. 2011, 6:e15871. doi: 10.1371/journal.pone.0015871.

Internal translation initiation stimulates expression of the ARF/core+1 open reading frame of HCV genotype 1b. Boumlic A., Vassilaki N., Dalagiorgou G., Kochlios E., Kakkanas A., Georgopoulou U., Markoulatos P., Orfanoudakis G., Mavromara P. Virus Res 2011, 155, 213-20. doi: 10.1016/j.virusres.2010.10.007.

Prevalence of intrinsic disorder in the hepatitis C virus ARFP/Core+1/S protein. Boumlic A., Nominé Y., Charbonnier S., Dalagiorgou G., Vassilaki N., Kieffer B., Travé G., Mavromara P., Orfanoudakis G. FEBS J 2010, 277, 774-89. doi: 10.1111/j.1742-4658.2009.07527.x

The HCV ARFP/F/core+1 protein: production and functional analysis of an unconventional viral product. Vassilaki N.* and Mavromara P.* IUBMB Life 2009, 61, 739-52. doi: 10.1002/iub.201 * Corresponding authors

Role of hepatitis C virus core+1 open reading frame and core cis-acting RNA elements in viral RNA translation and replication. Vassilaki N., Friebe P., Meuleman P., Kallis S., Kaul A., Paranhos-Baccalà G., Leroux-Roels G., Mavromara P. and Bartenschlager R. J Virol 2008, 82, 11503-15. doi: 10.1128/JVI.01640-08.

Expression studies of the HCV-1a core+1 open reading frame in mammalian cells. Vassilaki N., Boleti H. and Mavromara P. Virus Res 2008, 133, 123-135. doi: 10.1016/j.virusres.2007.10.019.

Differences in the expression of the hepatitis C virus core+1 open reading frame between a nuclear and a cytoplasmic expression system. Vassilaki N., Kalliampakou K.I. and Mavromara P. J Gen Virol 2008, 89, 222-231. doi: 10.1099/vir.0.83260-0

Expression studies of the core+1 protein of the hepatitis C virus 1a in mammalian cells. The influence of the core protein and proteasomes on the intracellular levels of core+1. Vassilaki N., Boleti H., Mavromara P. FEBS J. 2007, 274, 4057-4074. doi: 10.1111/j.1742-4658.2007.05929.x

HCV-associated hepatocellular carcinoma. Vassilaki N., Khalili S. and Mavromara P. In Viral Oncogenesis 2006 (Tognon M, eds), pp 145-181. Research Signpost Press, Kerala, India.

Two alternative mechanisms are responsible for the synthesis of HCV ARFP/F/core+1. Vassilaki N. and Mavromara P. J Biol Chem 2003, 278, 40503−40513. doi: 10.1074/jbc.M305504200

Alternate translation occurs within the core-coding region of the hepatitis C viral genome. Varaklioti A., Vassilaki N., Georgopoulou U., and Mavromara P. J Biol Chem 2002, 277, 17713-17721. doi: 10.1074/jbc.M201722200

2011

High Levels of HCV core+1 Antibodies in HCV Patients with Hepatocellular Carcinoma. Dalagiorgou G., Vassilaki N., Foka P., Boumlic A., Kakkanas A., Kochlios E., Khalili S., Aslanoglou E., Veletza S., Orfanoudakis G., Vassilopoulos D., Hadziyannis S., Koskinas J., Mavromara P. J Gen Virol. 2011, 92: 1343-51. doi: 10.1099/vir.0.023010-0.

Synonymous mutations in the core gene are linked to unusual serological profile in hepatitis C virus infection. Budkowska A., Kakkanas A., Nerrienet E., Kalinina O., Maillard P., Horm S.V., Dalagiorgou G., Vassilaki N., Georgopoulou U., Martinot M., Sall A.Α., and Mavromara P. PLoS One. 2011, 6:e15871. doi: 10.1371/journal.pone.0015871.

Internal translation initiation stimulates expression of the ARF/core+1 open reading frame of HCV genotype 1b. Boumlic A., Vassilaki N., Dalagiorgou G., Kochlios E., Kakkanas A., Georgopoulou U., Markoulatos P., Orfanoudakis G., Mavromara P. Virus Res 2011, 155, 213-20. doi: 10.1016/j.virusres.2010.10.007.

2010

Prevalence of intrinsic disorder in the hepatitis C virus ARFP/Core+1/S protein. Boumlic A., Nominé Y., Charbonnier S., Dalagiorgou G., Vassilaki N., Kieffer B., Travé G., Mavromara P., Orfanoudakis G. FEBS J 2010, 277, 774-89. doi: 10.1111/j.1742-4658.2009.07527.x

2009

The HCV ARFP/F/core+1 protein: production and functional analysis of an unconventional viral product. Vassilaki N.* and Mavromara P.* IUBMB Life 2009, 61, 739-52. doi: 10.1002/iub.201 * Corresponding authors

2008

Role of hepatitis C virus core+1 open reading frame and core cis-acting RNA elements in viral RNA translation and replication. Vassilaki N., Friebe P., Meuleman P., Kallis S., Kaul A., Paranhos-Baccalà G., Leroux-Roels G., Mavromara P. and Bartenschlager R. J Virol 2008, 82, 11503-15. doi: 10.1128/JVI.01640-08.

Expression studies of the HCV-1a core+1 open reading frame in mammalian cells. Vassilaki N., Boleti H. and Mavromara P. Virus Res 2008, 133, 123-135. doi: 10.1016/j.virusres.2007.10.019.

Differences in the expression of the hepatitis C virus core+1 open reading frame between a nuclear and a cytoplasmic expression system. Vassilaki N., Kalliampakou K.I. and Mavromara P. J Gen Virol 2008, 89, 222-231. doi: 10.1099/vir.0.83260-0

2007

Expression studies of the core+1 protein of the hepatitis C virus 1a in mammalian cells. The influence of the core protein and proteasomes on the intracellular levels of core+1. Vassilaki N., Boleti H., Mavromara P. FEBS J. 2007, 274, 4057-4074. doi: 10.1111/j.1742-4658.2007.05929.x

2006

HCV-associated hepatocellular carcinoma. Vassilaki N., Khalili S. and Mavromara P. In Viral Oncogenesis 2006 (Tognon M, eds), pp 145-181. Research Signpost Press, Kerala, India.

2003

Two alternative mechanisms are responsible for the synthesis of HCV ARFP/F/core+1. Vassilaki N. and Mavromara P. J Biol Chem 2003, 278, 40503−40513. doi: 10.1074/jbc.M305504200

2002

Alternate translation occurs within the core-coding region of the hepatitis C viral genome. Varaklioti A., Vassilaki N., Georgopoulou U., and Mavromara P. J Biol Chem 2002, 277, 17713-17721. doi: 10.1074/jbc.M201722200

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