Stefan S. Nicolau Institute of Virology – 2020-2021

As it was a period marked by the COVID-19 pandemic, the researchers of the Stefan S. Nicolau Institute of Virology, in addition to their current fundamental and applied research activities in priority research areas, offered to serve the national public health system. Following the Order of the Minister of Health no. 639/21.04.2020, the Institute of Virology was integrated into the list of specialized units implementing the National Program for the Surveillance and Control of Priority Communicable Diseases. Since March 2021, by Order of the Minister of Health no. 383/18.03.2021, it was nominated as a regional laboratory (half of the southeast region) for the screening of SARS-CoV-2 viral variants.

The departments “Cellular and Molecular Pathology”, “Molecular Virology”, “Emerging Viral Diseases”, “Strategy, Education, Documentation, IT”, “Immunology Center”, as well as the financial and administrative structures, have been actively involved in testing for SARS-CoV-2 both for the Public Health Department and in various projects initiated by national authorities, currently having a biobank of over 4400 samples that have served as the basis material for the identification research through next-generation sequencing (NGS) of circulating SARS-CoV-2 variants.

To date, over 50 viral isolates have been tested by NGS, by attracting donations from the “Always Close Foundation” and the “Foundation for Molecular and Cellular Medicine,” with a large part of these sequences already disseminated to the international community by publication in GISAID, the most important database of SARS-CoV-2 sequences and associated clinical and epidemiological data.

Also, following the updating and validation of the level 3 biosafety laboratory (BSL-3), with the support of the Romanian Academy, several SARS CoV-2 viral variants could be isolated and characterized from biological samples from our sample bank, strains that, following the sequencing of the entire viral genome on our NGS platform (Illumina), were associated with the following viral variants: a) B.1.408; B.1.258; B.1.88; b) starting from March 2021, the B.1.1.7 (VOC) variant, c) exclusively the B.1.617.2 (delta) variant since July 2021.

As a result of the start of the national vaccination campaign, initially targeting healthcare personnel as a priority group, a collaboration was initiated with the National Institute of Public Health and 3 major hospitals in the capital (Victor Babeș Hospital for Infectious and Tropical Diseases, Emergency University Hospital, Carol Davila Nephrology Hospital) for the longitudinal evaluation of the immune status post-vaccination and the dynamics of anti-SARS-CoV-2 antibodies in anti-COVID-19 vaccinated medical personnel. Over 500 people were enrolled, from whom longitudinal samples will be obtained at 0, 3, 6, 9, 12 months post-vaccination.

The study will provide important information on the duration of the immune response after vaccination, contribute to the evaluation of vaccination efficacy and the assessment of the rate of asymptomatic post-vaccination infections, as well as to the establishment of markers associated with protection. Another important project within the Romanian Academy’s current research program for 2021 is focused on studying the prognostic factors of COVID-19 evolution. Within this project, a serum bank has already been created from over 500 patients hospitalized at the Victor Babeș Hospital with a diagnosis of SARS CoV-2 infection, who have benefited from different therapeutic schemes. The association between severe evolution and the level of proinflammatory cytokines and chemokines, as well as the effectiveness of targeted therapies (monoclonal antibodies inhibiting IL-6 or IL-1 receptors), is being evaluated. Also, correlations between the severity of SARS-CoV-2 infection, viral variants, and specific host molecular markers have been investigated.

The Stefan S. Nicolau Institute of Virology (IVN) has promoted international collaboration and interdisciplinary and multidisciplinary research, winning prestigious European-funded projects with international partners. Currently, the EU-Horizon 2020 STAMINA project is being implemented, which will develop a multinational partnership of intelligent decision support tools for predicting and managing pandemics, as well as guidelines for effective implementation of principles and good practices to be applied in risk communication and preparedness and response plans. PERISCOPE, also an EU-Horizon 2020 project, in partnership with 32 countries, will analyze the impact of the COVID-19 pandemic on vulnerable and overexposed groups employed in the “front line.”

These research directions generated by the COVID-19 pandemic have resulted in various publications, including those by the Stefan S. Nicolau Institute of Virology:

Book chapters:

  • Simona Ruta, Capitolul: Perspectivele vaccinării împotriva COVID-19 – în monografia “Pandemia COVID-19 in Romania – aspecte Clinice si Epidemiologice“, Editura Academiei Romane, 2020, sub coordonarea Acad V. Voicu, C. Cernescu, I Popescu.
  • Simona RutaCostin Cernescu,Capitolul: Vaccinuri anti SARS CoV-2 –  în monografia “Pandemia COVID-19 în România“ vol. II, Aspecte patogenice, clinice și farmacoterapeutice” Editura Academiei Române 2021, sub coordonarea Acad V. Voicu, I Popescu.

Scientific articles:

  • Popescu CP, Marin A, Melinte V, Gherlan GS, Banicioiu FC, Dogaru A, Smadu S,Veja AM, Nedu E, Stanciu D, Voinescu B, Simion V, Toderan A, Dascalu A, Oprisan C, Tardei G, Nica M, Ceausu E, Ruta SM, Florescu SA. COVID-19 in a tertiary hospital from Romania: Epidemiology, preparedness and clinical challenges. TRAVEL MED INFECT DIS 2020 Apr 10:101662. doi: 10.1016/j.tmaid.2020.101662. [Epub ahead of pri PubMed PMID: 32283216; PubMed Central PMCID: PMC7151488. FI=6.211
  • Arsene, AL; Dumitrescu, IB ; Dragoi, CM; Udeanu, DI ; Lupuliasa, D , Jinga, V ; Draganescu, D ; Dinu-Pirvu, CE , Dragomiroiu, GTAB ; Blejan, IE ; Moisi, RE ; Nicolae, AC ; Moldovan, H ; Popa, DE ; Velescu, BS ; Ruta S. A new era for the therapeutic management of the ongoing COVID-19 pandemic. FARMACIA: 68, 2,185-196, 2020.
  • Botezatu A, Iancu V I, Plesa A, Huica I, Fudulu A, Albulescu A, Anton G, Molecular and Serological Prospects for SARS-CoV2 Epidemiology, PHARMACOPHORE, 2020, 11(6), 122-131
  • Bostan M, Ataman M, Bostan S I, Bleotu C, Targets and Assay Types for COVID-19 Diagnosis. J IMMUNOASSAY AND IMMUNOCHEM, 946-959, 2021.
  • Radu M C, Boeru C, Marin M, Manolescu LSC. SARS-CoV-2 Infection in Seven Childbearing Women at the Moment of Delivery, a Romanian Experience. 2021.CUREUS 13(1): e12811. doi:10.7759/cureus.12811.
  • Steiner N., Zaharia C.N., Updated preparation framework and response a pandemic flu, MANAGEMENT IN HEALTH, XXIV, 5-9, 2020.
  • Manolescu, L.S.C.; Zaharia, C.N.; Dumitrescu, A.I., Prasacu, I., Radu, M.C., Boeru, A.C., Boidache, L., Nita, I., Necsulescu, A., Chivu, R.D. Early COVID-19 Vaccination of Romanian Medical and Social Personnel. VACCINES (Basel) 2021, 9, 1127.
  • Bălan A, Bejan I, Bonciu S, Eni CE, Ruță S. Romanian Medical Students’ Attitude towards and Perceived Knowledge on COVID-19 Vaccination. VACCINES (Basel). 2021 Aug 4;9(8):854. doi: 10.3390/vaccines9080854. PMID: 34451979; PMCID: PMC8402573, IF=4.422.

Scientific communications and presentations:

  • Diaconu CC, Mambet C, Chivu-Economescu M, Bleotu C, Neagu AI, Necula LG, Matei L, Dragu LD, Pitică I, Năstasie A, Botezatu A, Iancu I, Nedeianu S, Anton G, Molecular diagnosis of SARS-CoV-2 infection, Comunicări orale susținute la A Patra Conferință a Asociației de Medicină de Laborator din România desfășurată online în perioada 09-11 septembrie 2020, Abstract publicat în REVISTA ROMÂNĂ DE MEDICINĂ DE LABORATOR, 28S1, 4, S41, 2020.
  • Simona Ruță. Vaccinuri SARS-CoV-2 – între speranţe şi incertitudini. A XIII-a Conferinţă Naţională de Microbiologie şi Epidemiologie, 29-31 octombrie 2020, Iasi – online, rezumat publicat în revista BACTERIOLOGIA, VIRUSOLOGIA, PARAZITOLOGIA, EPIDEMIOLOGIA, 65(3-4), 2020, p16-17 , ISSN: 1220-3696
  • Laura-Denisa Dragu, Ioan Călinescu, Simona Maria Ruţă, Alina Cherecheanu Popa, Sînziana Istrate, Anda Băicuş, Mariana Costache, Mircea Vînătoru, Coralia Bleotu. Evaluarea proprietăților antivirale ale materialelor impregnate cu combinații de nanoparticule de oxid de cupru și de zinc. A XIII-a Conferinţă Naţională de Microbiologie şi Epidemiologie, 29-31 octombrie 2020, Iasi -online, rezumat publicat în revista BACTERIOLOGIA, VIRUSOLOGIA, PARAZITOLOGIA, EPIDEMIOLOGIA,  P7, 65(3-4), 2020, pg 82-83 , ISSN: 1220-3696
  • Simona Ruță, Variante virale: un punct de cotitură în evoluţia pandemiei COVID-19?- Conferinta Academiei de Stiinte Medicale din Romania « Primul an de pandemie COVID-19. Dovezi ştiinţifice. Experienţe proprii » 15 martie 2021
  • Simona Ruță, Necunoscutele vaccinării antiCOVID-19– A treiaediție a Conferinței Naționale Multidisciplinară Endocrinologia- abordare în era COVID 19 – 20 martie 2021
  • Simona Ruță, Evolutii in dezvoltarea vaccinurilor impotriva COVID-19 – a IX-a ediție a Conferinței Naționale RoVaccin 26 – 28 martie 2021
  • Simona Ruță, Variante virale – implicații pentru evoluția pandemiei COVID-19, a IX-a Conferință a Colegiului Medicilor din Municipiul București , 21-24 aprilie 2021
  • Mihaela Economescu, Camelia Grancea, Coralia Bleotu, Carmen Diaconu, Simona Ruță Evaluarea răspunsului imun post vaccinare la personalul medical din Institutul de Virusologie „Ștefan S. Nicolau” Webinar  Experiența Spitalului Clinic de Boli Infecțioase și Tropicale “Dr. Victor Babeș” la 1 an de pandemie COVID-19,  8-9 aprilie 2021, .

In parallel, 9 other research projects funded from Structural Funds – Operational Competitiveness Program, EU-Horizon 2020-ERANET, PNIII Program, etc. were carried out in the Institute.

As a result of the research activity within these projects, several other articles indexed in Web of Science (WOS – Clarivate Analytics) have already been published in 2021 alone.

We mention some of these works resulting from the projects carried out during this period at the Stefan S. Nicolau Institute of Virology:

  • D’haese S, Lacroix C, Garcia F, Plana M, Ruta S, Vanham G, Verrier B, Aerts JL. Off the beaten path: Novel mRNA-nanoformulations for therapeutic vaccination against HIV. J CONTROL RELEASE. 2021 Feb 10;330:1016-1033. doi: 10.1016/j.jconrel.2020.11.009. Epub 2020 Nov 10. PMID: 33181204. FI 9.776
  • Popescu CP, Cotar AI, Dinu S, et al. Emergence of Toscana Virus, Romania, 2017-2018. EMERG INFECT DIS. 2021;27(5):1482-1485. doi:10.3201/eid2705.204598 FI 6.883
  • Popescu CP, Zaharia M, Nica M, Delia Stanciu, Ruxandra Moroti, Serban Benea, Violeta Melinte, Teodor Vasile, Emanoil Ceausu, Simona Ruta, Simin Aysel Florescu. Anthrax meningoencephalitis complicated with brain abscess—A case reportINTERNATIONAL JOURNAL OF INFECTIOUS DISEASES. In press. Available online 12 May 2021 FI 3.623
  • Radu MC, Dumitrescu A I, Zaharia CN, Boeru C, Pop-Tudose ME, Iancu CF, Chivu RD. (March 12, 2021) Teenage Pregnancies and Childbirth Experience in Romania From the Midwives Point of View. CUREUS 13(3): e13851. DOI 10.7759/cureus.13851.
  • Radu M C, Boeru C, Pop-Tudose M, Necsulescu A, Dumitrescu A,Iancu CF, Nita I, Limbau AM, Zaharia CN.(June 01, 2021) Human Papillomavirus Infection at the Time of Delivery. CUREUS 13(6): e15364. DOI 10.7759/cureus.15364.
  • Fudulu A, Olar R, Maxim C, Scaeteanu, GV, Bleotu C, Matei L, Chifiriuc C, Badea M,  New Cobalt (II) Complexes with Imidazole Derivatives: Antimicrobial Efficiency against Planktonic and Adherent Microbes and In Vitro Cytotoxicity Features, MOLECULES, 2021,  26, Article Number: 55, DOI: 10.3390/molecules26010055 IF=4.412 – Articol premiat UEFISCDI
  • Amfim A, Botezatu A, Anton G, Burlibasa L, Zarnescu O, Albu C, Matei M, Tanase A, Radu LG, Alexandrescu L, Cucu N, Canine Model for the Study of the Epigenetic Factors Involved in Mammary Tumor Development, BIOINTERFACE RESEARCH IN APPLIED CHEMISTRY, 2021, 11, 7543-7557, DOI: 10.33263/BRIAC111.75437557, IS= 1.95
  • Hotoboc IE, Fudulu A, Grigore R, Bertesteanu S, Huica I, Iancu IV, Botezatu A, BleotuC, Anton G, The association between lncRNA H19 and EZH2 expression in patients with EBV-positive laryngeal carcinoma. ACTA OTORHINOLARYNGOLOGICA ITALICA, 2021; 41:1-7. IF= 2.124
  • Negrila CC, Predoi D, Ghita RV, Iconaru SL, Ciobanu SC, Manea M, Badea ML, Costescu A, Trusca R, Predoi G, Stanciu GA, Hristu R, Dragu LD, Bleotu C, Groza A, Marinas IC, Chifiriuc MC, Multi-Level Evaluation of UV Action upon Vitamin D Enhanced, Silver Doped Hydroxyapatite Thin Films Deposited on Titanium Substrate, COATINGS, 2021, 11 (2), 120, 10.3390/coatings11020120, WOS:000622409300001. IF= 2.881
  • Gheorghe I, Avram I, Corbu VM, Marutescu L, Popa M, Balotescu I, Blajan I, Mateescu V, Zaharia D, Dumbrava AS, Zetu OE, Pecete I, Cristea VC, Batalu D, Grigoroscuta MA, Burdusel M, Aldica GV, Badica P, Datcu AD, Ianovici N, Bleotu C, Lazar V, Ditu LM, Chifiriuc MC, In Vitro Evaluation of MgB2 Powders as Novel Tools to Fight Fungal Biodeterioration of Heritage Buildings and Objects, FRONTIERS IN MATERIALS, 2296-8016, 2021, 7, 601059, 10.3389/fmats.2020.601059, WOS:000615911800001 IF= 3.515
  • Stroe, R; Mambet, C; Curici, A; Ivan, F; Alexa, L; Morjan, C; Hodis, N; Matei, L; Dragu, LD; Lazar, V; Bleotu, C,  Differential expression of NLRP3 inflammasome genes in HPV infected cervical cells, ROMANIAN BIOTECHNOLOGICAL LETTERS, 1224-5984, 2021, 26 (1), 2255-2261, 10.25083/rbl/26.1/2255.2261, WOS:000596730800009
  • Tiplea, RE; Lemnaru, GM; Trusca, RD; Holban, A; Kaya, MGA; Dragu, LD; Ficai, D; Ficai, A; Bleotu, C, Antimicrobial Films based on Chitosan, Collagen, and ZnO for Skin Tissue Regeneration. BIOINTERFACE RESEARCH IN APPLIED CHEMISTRY, 2069-5837, 2021, 11, (4),11985-11995, 10.33263/BRIAC114.1198511995, WOS:000606325300065
  • Tihauan, BM; Marinas, IC; Bleotu, C; Dolete, G; Onisei, T; Serbancea, F; Mateescu, C; Rascol, M, Evaluation of cytotoxicity, nutritional and anti-oxidative status of lyophilized plant extracts used in dietary supplements, ROMANIAN BIOTECHNOLOGICAL LETTERS, 1224-5984, 2021, 26 (2), 396-2405, 10.25083/rbl/26.2/2396.2405, WOS:000609625200005
  • Neacsu, IA; Leau, SA; Marin, S; Holban, AM; Vasile, BS; Nicoara, AI; Ene, VL; Bleotu, C; Kaya, MGA; Ficai, A, Collagen-Carboxymethylcellulose Biocomposite Wound-Dressings with Antimicrobial Activity, MATERIALS, 2021, 14 (5), 1153, 10.3390/ma14051153, WOS:000628385900001. IF= 3.057
  • Badea, M; Grecu, MN; Chifiriuc, MC; Bleotu, C; Popa, M; Iorgulescu, EE; Avram, S; Uivarosi, V; Munteanu, AC; Ghica, D; Olar, R, Insight on Ni(II) and Cu(II) complexes of biguanide derivatives developed as effective antimicrobial and antitumour agents, APPLIED ORGANOMETALLIC CHEMISTRY, 0268-2605, 2021, 35 (4), e6155, 10.1002/aoc.6155, WOS:000612685900001 IF = 3.14
  • Visan AI, Ristoscu C, Popescu-Pelin G, Sopronyi M, Matei CE, Socol G, Chifiriuc MC, Bleotu C, Grossin D, Brouillet F, Grill SL, Bertrand G, Zgura I, Cristescu R, Mihailescu IN. Composite Drug Delivery System Based on Amorphous Calcium Phosphate-Chitosan: An Efficient Antimicrobial Platform for Extended Release of Tetracycline. PHARMACEUTICS. 2021 Oct 11;13(10):1659. doi: 10.3390/pharmaceutics13101659. PMID: 34683952, IF=6.321
  • Chivu-Economescu M, Necula L, Matei L, Dragu D, Bleotu C, Diaconu CC. Clinical Applications of Liquid Biopsy in Gastric Cancer. FRONT MED (Lausanne). 2021 Sep 28;8:749250. doi: 10.3389/fmed.2021.749250. eCollection 2021. PMID: 34651002, IF=5.091
  • Camelia Elena Stecoza, George Mihai Nitulescu, Constantin Draghici, Miron Teodor Caproiu, Octavian Tudorel Olaru, Marinela Bostan and Mirela Mihaila. Synthesis and Anticancer Evaluation of New 1,3,4-Oxadiazole Derivatives. PHARMACEUTICALS, 14, 438-453, 2021, IF=5.863
  • Munteanu, Alexandra-Cristina; Musat, Mihaela Georgiana; Mihaila, Mirela; et al. New heteroleptic lanthanide complexes as multimodal drugs: Cytotoxicity studies, apoptosis, cell cycle analysis, DNA interactions, and protein binding, APPLIED ORGANOMETALLIC CHEMISTRY  35(1): 1-22, e6062   Published: ‏ JAN 2021, IF= 4.105
  • Veronica Madalina Aspriţoiu, Ileana Stoica, Coralia Bleotu and Carmen Cristina Diaconu:  Epigenetic Regulation of Angiogenesis in Development and Tumors Progression: Potential Implications for Cancer Treatment, FRONT CELL DEV BIOL, 06 September 2021; IF=6.684
  • Iancu IV, Botezatu A, Pleșa A, Huică I, Fudulu A, Albulescu A, Bostan M, Mihăilă M, Grancea C, Manda DA, Dobrescu R, Vlădoiu SV, Anton G, Badiu CV. Alterations of regulatory factors and DNA methylation pattern in thyroid cancer. CANCER BIOMARKERS, 2020, 28: 255–268. DOI: 10.3233/CBM-190871.  IF=4.388 – Articol premiat UEFISCDI
  • Albulescu A, Plesa A, Fudulu A, Iancu IV, Anton G, Botezatu A. Epigenetic approaches for cervical neoplasia screening. EXPERIMENTAL AND THERAPEUTIC MEDICINE. 2021; 22:1481 .  IF= 2.447
  •  Păvăloiu RD, Sha’at F, Neagu G, Deaconu M, Bubueanu C, Albulescu A, Sha’at M, Hlevca C. Encapsulation of Polyphenols from Lycium barbarum Leaves into Liposomes as a Strategy to Improve Their Delivery. NANOMATERIALS 2021;11(8):1938. . IF = 5.346 – Articol premiat UEFISCDI
  •  Neagu G, Stefaniu A, Albulescu A, Pintilie L, Pirvu LC. Antiproliferative activity of Stokesia laevis ethanolic extract in combination with several food-related bioactive compounds; in vitro (Caco2) and in silico docking (TNKS1) studies. Applied Sciences. Appl. Sci. 2021;11(21):9944. 2.679
  • Marinela BostanMirela MihailaGeorgiana Gabriela Petrica-MateiNicoleta RaduRazvan HainarosieCristian Dragos StefanescuViviana RomanCarmen Cristina Diaconu. Resveratrol modulation of apoptosis and cell cycle response to cisplatin in head and neck cancer cell lines. INT J MOL SCI, 22(12), 6322-6342, 2021 IF= 5.923 – Articol premiat UEFISCDI
  • Gabriela Ion, Juliana A AkinseteTheodore R Witte, Marinela Bostan, W. Elaine Hardman. Maternal fish oil consumption has a negative impact on mammary gland tumorigenesis in C3(1) Tag mice offspring. EUR J OF NUTRITION, March 2021, pp1-11,, part of Springer Nature 2021, IF=5.286
  • Mirela Mihaila, Camelia Mia Hotnog, Marinela Bostan, Alexandra Cristina Munteanu, Ileana Adela Vacaroiu, Lorelei Irina Brasoveanu, Valentina Uivarosi. Anticancer activity of some ruthenium (III) complexes with quinolone antibiotics: In vitro cytotoxicity, cell cycle modulation, and apoptosis-inducing properties in LoVo colon cancer cell line. APPL SCI11(18), 8594-8613, 2021, IF=2.679
  • Ioana LacatusuTeodora Alexandra IordacheMirela MihailaDan Eduard MihaiescuAnca Lucia PopNicoleta Badea. Multifaced role of dual herbal principles loaded-lipid nanocarriers in providing high therapeutic efficacity. PHARMACEUTICS, 13(9), 1511-1534, 2021, IF= 6.321

Scientific communications and presentations:

  • Alexandra-Cristina Munteanu, Mirela Mihaila, George Mihai Nitulescu, Valentina Uivarosi. Ruthenium (II) octahedral complexes featuring pyrimidine-like ligands: cytotoxicity and DNA/protein interaction studies. GP2A 2021 – 29th Annual Conference, 25-27.08.2021
  • Alexandra-Cristina Munteanu, Mirela Mihaila, Joseph Cowell, Gilles Gasser, Valentina Uivarosi. Osmium (II) octahedral complexes featuring orotic acid: anticancer activity and DNA/protein interaction studies, 1st OncoHub Conference, 13-15.10.2021 (poster premiat)
  • M. DumitruM. MihailaC.M. Hotnog, M.E. Panait, M.M. Vasilescu, M.G. Hortopan, L.I. Brasoveanu. HER2 expression in primary bladder tumors and paired regional lymph nodes: Relationship to cell cycle profileANNALS OF ONCOLOGY, 32(6), October 2021
  • Camelia Elena Stecoza, George Mihai Nitulescu, Constantin Draghici, Miron Teodor Caproiu, Octavian Tudorel Olaru, Marinela Bostan, Mirela Mihaila. New 1,3,4 – oxadiazole derivatives and their role in tumor processes. 7th International Electronic Conference on Medicinal Chemistry, 1–30 Nov 2021
  • Camelia Elena Stecoza, George Mihai Nitulescu, Constantin Draghici, Miron Teodor Caproiu, Diana Nuta, Marinela Bostan, Mirela Mihaila. Analysis of the antitumor capacity of some new 1,3,4-oxadiazole-based heterocycles. Congresul Universitatii de Medicina si Farmacie “Carol Davila”, 25-27.11.2021
  • Botezatu A, Plesa A, Iancu IV, Bostan M, Mihaila M, Albulescu A, Fudulu A, C. Diaconu, Anton G. E6 and E7 HPV16 oncogenes influence gene transcription trough the genome-wide pattern deposition of MBD2/3 components of NuRD nucleosome remodeling complex. ESHG 2021- European Human Genetics Virtual Conference, august 28-31, 2021