Louis Papageorgiou

Structural models for the design of novel antiviral agents against Greek Goat Encephalitis.

The Greek Goat Encephalitis virus (GGE) belongs to the Flaviviridae family of the genus Flavivirus. The GGE virus constitutes an important pathogen of livestock that infects the goat’s central nervous system. The viral enzymes of GGE, helicase and RNA-dependent RNA polymerase (RdRP), are ideal targets for inhibitor design, since those enzymes are crucial for the virus’ survival, proliferation and transmission. In an effort to understand the molecular structure underlying the functions of those viral enzymes, the three dimensional structures of GGE NS3 helicase and NS5 RdRP have been modelled. The models were constructed in silico using conventional homology modelling techniques and the known 3D crystal structures of solved proteins from closely related species as templates. The established structural models of the GGE NS3 helicase and NS5 RdRP have been evaluated for their viability using a repertoire of in silico tools. The goal of this study is to present the 3D conformations of the GGE viral enzymes as reliable structural models that could provide the platform for the design of novel anti-GGE agents.

Human Emotions on the Onset of Cardiovascular and Small Vessel Related Diseases

Background/Aim: The aim of the present study was to examine the relation between understanding of emotions and cardiovascular related diseases, namely coronary heart disease, diabetes mellitus and obesity. The uniqueness of this study lies in the fact that it examined the relationship between the cardiovascular related diseases named above and the understanding of emotions in the context of Emotional Intelligence (EI). Patients and Methods: The study was conducted in 300 participants during a 3 year period. All participants completed a self-report questionnaire, assessing various aspects of EI, such as self-emotion appraisal, other emotion appraisal, emotion regulation and use of emotions. As hypothesized, coronary heart disease is a prognostic factor of regulation of emotions. Results: The present study is an attempt to examine the relation between emotional understanding and cardiovascular related diseases, namely coronary heart disease, diabetes mellitus and obesity. Establishing which diseases are independent risk factors for the understanding of emotions, could have a significant impact on emotional health, through the treatment of these cardiovascular related diseases. Emotions were studied within the theoretical context of Emotional Intelligence (EI), which affects peoples physical and mental health. Conclusion: The results of this study emphasize on the relationship of cardiovascular related diseases and psychological characteristics, such as anxiety and anger, being aspects of EI. Additionally, this work fills a gap in the relevant Greek literature, as a first attempt to examine the correlation of EI with cardiovascular related diseases.

Carcinogenic Pesticide ControlviaHijacking Endosymbiosis; The Paradigm of DSB-A fromWolbachia pipientisfor the Management ofOtiorhynchus singularis

Background/Aim: Pesticides have little, if any specificity, to the pathogen they target in most cases. Wide spectrum toxic chemicals are being used to remove pestcides and salvage crops and economies linked to agriculture. The burden on the environment, public health and economy is huge. Traditional pestcide control is based on administering heavy loads of highly toxic compounds and elements that essentially strip all life from the field. Those chemicals are a leading cause of increased cancer related deaths in countryside. Herein, the Trojan horse of endosymbiosis was used, in an effort to control pests using high specificity compounds in reduced quantities. Materials and Methods: Our pipeline has been applied on the case of Otiorhynchus singularis, which is a very widespread pest, whose impact is devastating on a repertoire of crops. To date, there is no specific pesticide nor agent to control it. The deployed strategy involves the inhibition of the key DSB-A enzyme of its endosymbiotic Wolbachia pipientis bacterial strain. Results: Our methodology, provides the means to design, test and identify highly specific pestcide control substances that minimize the impact of toxic chemicals on health, economy and the environment. Conclusion: All in all, in this study a radical computer-based pipeline is proposed that could be adopted under many other similar scenarios and pave the way for precision agriculture via optimized pest control.

Genetic and structural study of DNA-directed RNA polymerase II of Trypanosoma brucei, towards the designing of novel antiparasitic agents

Trypanosoma brucei brucei (TBB) belongs to the unicellular parasitic protozoa organisms, specifically to the Trypanosoma genus of the Trypanosomatidae class. A variety of different vertebrate species can be infected by TBB, including humans and animals. Under particular conditions, the TBB can be hosted by wild and domestic animals; therefore, an important reservoir of infection always remains available to transmit through tsetse flies. Although the TBB parasite is one of the leading causes of death in the most underdeveloped countries, to date there is neither vaccination available nor any drug against TBB infection. The subunit RPB1 of the TBB DNA-directed RNA polymerase II (DdRpII) constitutes an ideal target for the design of novel inhibitors, since it is instrumental role is vital for the parasite’s survival, proliferation, and transmission. A major goal of the described study is to provide insights for novel anti-TBB agents via a state-of-the-art drug discovery approach of the TBB DdRpII RPB1. In an attempt to understand the function and action mechanisms of this parasite enzyme related to its molecular structure, an in-depth evolutionary study has been conducted in parallel to the in silico molecular designing of the 3D enzyme model, based on state-of-the-art comparative modelling and molecular dynamics techniques. Based on the evolutionary studies results nine new invariant, first-time reported, highly conserved regions have been identified within the DdRpII family enzymes. Consequently, those patches have been examined both at the sequence and structural level and have been evaluated in regard to their pharmacological targeting appropriateness. Finally, the pharmacophore elucidation study enabled us to virtually in silico screen hundreds of compounds and evaluate their interaction capabilities with the enzyme. It was found that a series of chlorine-rich set of compounds were the optimal inhibitors for the TBB DdRpII RPB1 enzyme. All-in-all, herein we present a series of new sites on the TBB DdRpII RPB1 of high pharmacological interest, alongside the construction of the 3D model of the enzyme and the suggestion of a new in silico pharmacophore model for fast screening of potential inhibiting agents.