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Approccio Multi Target e Multi Drug contro il CoV-2
SARS-CoV-2, responsible for Sars-Covid 19 infection, is an RNA virus belonging to the Coronavirus (Cov) family. This virus causes severe inflammation of the respiratory tract epithelium and can lead to the death of the affected patient. Currently, no definitive pharmacological therapies are available.
Under the electron microscope the virus appears as a crown (hence the name),because of the presence of spike glycoproteins (S) on its outer envelope, which facilitate the entry into the target cells. This process depends on the binding of the S1 unit of the S protein with a cellular receptor, which facilitates the attack of the virus on the surface of the target cells. In particular, it involves the angiotensin converting enzyme 2 (ACE2), as entry receptor, and the serine-protease TMPRSS2 for S protein activation.
The ACE2 receptor is an important protein that regulates the arterial vasoconstriction processes. This membrane protein is present on the lungs epithelium cells,protecting them from damages caused by infections and inflammations, the cardiac, renal and intestinal tissues. In the most severe cases, SARS-Cov-2 infection can cause acute inflammation in lung tissues, giving rise to interstitial pneumonia with a reduction of gas exchanges in the alveoli. Many derivatives taken into consideration by us have inhibitory activity against phosphodiesterases and in particular against PDE4. PDE4 is predominant in lung tissues, following its inhibition in inflammatory cells, there is an increase in AMPc, and this generates a bronchodilator effect.
As well as for other viral infections (e.g. Human Immunodeficiency Virus–HIV-, Hepatitis C virus–HCV-,hepatitis B virus–HBV-) a multitarget and multidrug therapeutic strategy, namely a pharmacological treatment supported by a rational multi-drug combination, could be beneficial.
This strategy will be focused on:
-preventing the ACE2 receptor binding;
-reducing the inflammation process;
-blocking the fibrin deposit on the alveoli;
-inhibiting the androgenic receptor, an unexpected target involved in SARS-Cov-2 infection .
The research team, therefore, aims to create a "multitarget and multidrug" system based on molecules made by total synthesis,in order to counteract the action of the virus on several fronts and at various levels.
The phylogenetic analysis will be used for the initial screening of SARS-Cov-2 sequences to check for phylogenetic clusters indicating genetic differences between the sequences. In addition, viral genome sequences will be analysed to detect mutations under positive selection and recombination events.
In vitro biological tests on selected compounds using the virus and cytotoxicity studies on non-infected human cells.
Prof.ssa Carmela Saturnino, Prof. Magnus Monnè e dott.ssa Federica Giuzio
1980: University of Naples, Degree in Pharmacy with voting: 110 cum laude; thesis in Medicinal Chemistry, entitled: etheroarylcarbossilic acids: preparation and anti-inflammatory activity.
July 1982: University of Naples (Postgraduate Diploma in Hospital Pharmacy vote: 50 cum laude).
June 1989:University L. Pasteur in Strasbourg (F) (.DEA - Pharmacologie et Pharmacochimie, option = Pharmacochimie. Supervisors prof.C.G.Wermuth and J.J.Bourguignon.
October 1990: University of Naples ,PhD in Pharmaceutical Sciences, the object of research: Imidazo-derivatived anti-inflammatory action, studies on structure-activity relationships and mechanism of action).
1991-1993: Fellow of the pharmaceutical industry -Servier in Paris and later the University of Caen (F).
September 1993 - October 2001: Department of Pharmaceutical Sciences - University of Salerno (researcher, in -Medicinal Chemistry).
From November 2001: Department of Pharmaceutical and Biomedical Sciences - University of Salerno (Associate Professor ,Medicinal Chemistry and Toxicology,CHIM08-disciplinary field).
April 2018, qualified to Full Professor (ASN) in Chemical Foundations of Technologies..and Medicinal Chemistry.
Co-author of over 140 papers in international scientific journals .Over 230 communications at national and international conferences. He has won several awards and research awards ,Co-author of 6 patents, some of which are PCTFounding member and Director of an academic spin off from the Title: TNcKillers s.r.l.. He has received awards and scientific awards in pharmaceutical research. Coordinates a research group that deals with the production of molecules with antitumor activity and in particular for TN breast cancer. In addition to the production of antitumor molecules, the research group is also involved in the synthesis of new heterocyclic compounds with antimicrobial activity and the realization of pharmaceutical formulations in which these molecules are trapped. The so-called drug delivery symptoms (membranes, liposomes, films, Au nanoparticles and graphenes) must allow the prolonged release of the molecules inserted in them.
September 2016, professor of Pharmaceutical Chemistry and Toxicology I and of Drugs Analysis 2, at the Department of Science, University of Basilicata, Potenza (Italy).
2018, qualified to Full Professor (ASN) in Chemical Foundations of Technologies..and Medicinal Chemistry
Researchlines: 1) Design, Synthesis and Biological studies of new Antitumor drugs.2) Organo-Metallic complexes with antimicrobial activity.3) Realization of DDS for the control release of drugs.