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  1. Article ; Online: In Vitro Combinatorial Activity of Direct Acting Antivirals and Monoclonal Antibodies against the Ancestral B.1 and BQ.1.1 SARS-CoV-2 Viral Variants.

    Fiaschi, Lia / Biba, Camilla / Varasi, Ilenia / Bartolini, Niccolò / Paletti, Chiara / Giammarino, Federica / Saladini, Francesco / Zazzi, Maurizio / Vicenti, Ilaria

    Viruses

    2024  Volume 16, Issue 2

    Abstract: Combination antiviral therapy may be helpful in the treatment of SARS-CoV-2 infection; however, no clinical trial data are available, and combined use of direct-acting antivirals (DAA) and monoclonal antibodies (mAb) has been reported only anecdotally. ... ...

    Abstract Combination antiviral therapy may be helpful in the treatment of SARS-CoV-2 infection; however, no clinical trial data are available, and combined use of direct-acting antivirals (DAA) and monoclonal antibodies (mAb) has been reported only anecdotally. To assess the cooperative effects of dual drug combinations in vitro, we used a VERO E6 cell-based in vitro system with the ancestral B.1 or the highly divergent BQ.1.1 virus to test pairwise combinations of the licensed DAA, including nirmatrelvir (NRM), remdesivir (RDV) and the active metabolite of molnupiravir (EIDD-1931) as well the combination of RDV with four licensed mAbs (sotrovimab, bebtelovimab, cilgavimab, tixagevimab; tested only with the susceptible B.1 virus). According to SynergyFinder 3.0 summary and weighted scores, all the combinations had an additive effect. Within DAA/DAA combinations, paired scores with the B.1 and BQ.1.1 variants were comparable. In the post hoc analysis weighting synergy by concentrations, several cases of highly synergistic scores were detected at specific drug concentrations, both for DAA/DAA and for RDV/mAb combinations. This was supported by in vitro confirmation experiments showing a more than a linear shift of a drug-effective concentration (IC
    MeSH term(s) Animals ; SARS-CoV-2/genetics ; Antiviral Agents/pharmacology ; COVID-19 ; Hepatitis C, Chronic ; Antibodies, Monoclonal/pharmacology ; Drug Combinations
    Chemical Substances Antiviral Agents ; Antibodies, Monoclonal ; Drug Combinations
    Language English
    Publishing date 2024-01-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v16020168
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: SARS-CoV-2 and influenza virus coinfections in the Tuscan population during the 2021/2022 influenza season.

    Milano, Giovanna / Marchi, Serena / Vicenti, Ilaria / Biba, Camilla / Fiaschi, Lia / Trombetta, Claudia Maria / Lazzeri, Giacomo / Montomoli, Emanuele / Manini, Ilaria

    Journal of preventive medicine and hygiene

    2024  Volume 65, Issue 1, Page(s) E11–E16

    Abstract: Introduction: The 2021/2022 influenza season was not characterised by a well-defined incidence peak. As reported by the Italian National Institute of Health, a high value of incidence of influenza cases was recorded in week 13, but it was still lower ... ...

    Abstract Introduction: The 2021/2022 influenza season was not characterised by a well-defined incidence peak. As reported by the Italian National Institute of Health, a high value of incidence of influenza cases was recorded in week 13, but it was still lower than in other influenza seasons. This abnormal circulation was probably due to relaxation of the COVID-19 pandemic restriction measures, such as social distancing, smart-working, home leaning and the use of masks, which greatly reduced the circulation of respiratory-transmitted viruses, including human respiratory syncytial virus (HRSV). The symptoms of SARS-CoV-2 and influenza are quite similar, sharing the human-to-human transmission route via respiratory droplets.
    Methods: The aim of this study was to estimate the rate of coinfection with influenza viruses and/or HRSV in SARS-CoV-2-positive subjects (N = 940) in a population of central Italy during the 2021/2022 season.
    Results: A total of 54 cases of coinfection were detected during the study period, 51 cases (5.4%) of SARS-CoV-2 and influenza virus and three cases (0.3%) of SARS-CoV-2 and HRSV coinfection.
    Conclusions: These results highlight the importance of continuous monitoring of the circulation of influenza virus and other respiratory viruses in the context of the COVID-19 pandemic.
    MeSH term(s) Humans ; Italy/epidemiology ; COVID-19/epidemiology ; Influenza, Human/epidemiology ; Coinfection/epidemiology ; Female ; Adult ; Male ; SARS-CoV-2 ; Child ; Middle Aged ; Child, Preschool ; Adolescent ; Aged ; Seasons ; Infant ; Young Adult ; Incidence ; Respiratory Syncytial Virus Infections/epidemiology
    Language English
    Publishing date 2024-03-31
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 1102926-2
    ISSN 2421-4248 ; 1121-2233
    ISSN (online) 2421-4248
    ISSN 1121-2233
    DOI 10.15167/2421-4248/jpmh2024.65.1.3179
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Does Nirmatrelvir/Ritonavir Influence the Immune Response against SARS-CoV-2, Independently from Rebound?

    Panza, Francesca / Fiorino, Fabio / Pastore, Gabiria / Fiaschi, Lia / Tumbarello, Mario / Medaglini, Donata / Ciabattini, Annalisa / Montagnani, Francesca / Fabbiani, Massimiliano

    Microorganisms

    2023  Volume 11, Issue 10

    Abstract: Recurrence of coronavirus disease 19 (COVID-19) symptoms and SARS-CoV-2 viral load relapse have been reported in people treated with nirmatrelvir/ritonavir (NM/r). However, little is understood about the etiology of this phenomenon. Our aim was to ... ...

    Abstract Recurrence of coronavirus disease 19 (COVID-19) symptoms and SARS-CoV-2 viral load relapse have been reported in people treated with nirmatrelvir/ritonavir (NM/r). However, little is understood about the etiology of this phenomenon. Our aim was to investigate the relation between the host's immune response and viral rebound. We described three cases of COVID-19 rebound that occurred after treatment with nirmatrelvir/ritonavir (group A). In addition, we compared spike-specific antibody response and plasma cytokine/chemokine patterns of the rebound cases with those of (i) control patients treated with nirmatrelvir/ritonavir who did not show rebound (group B), and (ii) subjects not treated with any anti-SARS-CoV-2 drug (group C). The anti-spike antibodies and plasma cytokines/chemokines were similar in groups A and B. However, we observed a higher anti-BA.2 spike IgG response in patients without antiviral treatment (group C) [geometric mean titer 210,807, 5.1- and 8.2-fold higher compared to group A (
    Language English
    Publishing date 2023-10-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720891-6
    ISSN 2076-2607
    ISSN 2076-2607
    DOI 10.3390/microorganisms11102607
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Serendipitous Identification of Azine Anticancer Agents Using a Privileged Scaffold Morphing Strategy.

    Cesarini, Silvia / Vicenti, Ilaria / Poggialini, Federica / Filippi, Silvia / Mancin, Eleonora / Fiaschi, Lia / De Marchi, Elisa / Giammarino, Federica / Vagaggini, Chiara / Bizzarri, Bruno Mattia / Saladino, Raffaele / Dreassi, Elena / Zazzi, Maurizio / Botta, Lorenzo

    Molecules (Basel, Switzerland)

    2024  Volume 29, Issue 7

    Abstract: The use of privileged scaffolds as a starting point for the construction of libraries of bioactive compounds is a widely used strategy in drug discovery and development. Scaffold decoration, morphing and hopping are additional techniques that enable the ... ...

    Abstract The use of privileged scaffolds as a starting point for the construction of libraries of bioactive compounds is a widely used strategy in drug discovery and development. Scaffold decoration, morphing and hopping are additional techniques that enable the modification of the chosen privileged framework and better explore the chemical space around it. In this study, two series of highly functionalized pyrimidine and pyridine derivatives were synthesized using a scaffold morphing approach consisting of triazine compounds obtained previously as antiviral agents. Newly synthesized azines were evaluated against lymphoma, hepatocarcinoma, and colon epithelial carcinoma cells, showing in five cases acceptable to good anticancer activity associated with low cytotoxicity on healthy fibroblasts. Finally, ADME in vitro studies were conducted on the best derivatives of the two series showing good passive permeability and resistance to metabolic degradation.
    MeSH term(s) Humans ; Antineoplastic Agents/pharmacology ; Antiviral Agents/pharmacology ; Azo Compounds ; Carcinoma, Hepatocellular ; Liver Neoplasms
    Chemical Substances Antineoplastic Agents ; Antiviral Agents ; Azo Compounds
    Language English
    Publishing date 2024-03-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules29071452
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Comparable Post-Vaccination Decay of Neutralizing Antibody Response to Wild-Type and Delta SARS-CoV-2 Variant in Healthcare Workers Recovered from Mild or Asymptomatic Infection.

    Vicenti, Ilaria / Basso, Monica / Dragoni, Filippo / Gatti, Francesca / Scaggiante, Renzo / Fiaschi, Lia / Parisi, Saverio G / Zazzi, Maurizio

    Vaccines

    2022  Volume 10, Issue 4

    Abstract: We described the long-term decay of neutralizing antibody (NtAb) to the wild-type and Delta SARS-CoV-2 variant after three antigen stimulations (mild or asymptomatic natural infection followed by two doses of the BNT162b2 mRNA vaccine after a median of ... ...

    Abstract We described the long-term decay of neutralizing antibody (NtAb) to the wild-type and Delta SARS-CoV-2 variant after three antigen stimulations (mild or asymptomatic natural infection followed by two doses of the BNT162b2 mRNA vaccine after a median of 296 days) in immunocompetent healthcare workers (HCWs). Live virus microneutralization against the B.1 and Delta SARS-CoV-2 variants was performed in VERO E6 cell cultures. The median NtAb titers for B.1 and Delta were comparable and highly correlated at both 20 and 200 days after the second vaccine dose in the 23 HCWs enrolled (median age, 46 years). A small group of naturally infected unvaccinated HCWs had comparable NtAb titers for the two strains after a median follow-up of 522 days from infection diagnosis. The NtAb response to the Delta VoC appears to follow the same long-term dynamics as the wild-type response regardless of the vaccinal boost; data collected after three antigen stimulations (natural infection followed by two doses of the BNT162b2 mRNA vaccine) may be helpful for tailoring the continuous monitoring of vaccine protection against SARS-CoV-2 variants over time.
    Language English
    Publishing date 2022-04-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines10040580
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Efficacy of Licensed Monoclonal Antibodies and Antiviral Agents against the SARS-CoV-2 Omicron Sublineages BA.1 and BA.2

    Fiaschi, Lia / Dragoni, Filippo / Schiaroli, Elisabetta / Bergna, Annalisa / Rossetti, Barbara / Giammarino, Federica / Biba, Camilla / Gidari, Anna / Lai, Alessia / Nencioni, Cesira / Francisci, Daniela / Zazzi, Maurizio / Vicenti, Ilaria

    Viruses. 2022 June 23, v. 14, no. 7

    2022  

    Abstract: Newly emerging SARS-CoV-2 variants may escape monoclonal antibodies (mAbs) and antiviral drugs. By using live virus assays, we assessed the ex vivo inhibition of the B.1 wild-type (WT), delta and omicron BA.1 and BA.2 lineages by post-infusion sera from ... ...

    Abstract Newly emerging SARS-CoV-2 variants may escape monoclonal antibodies (mAbs) and antiviral drugs. By using live virus assays, we assessed the ex vivo inhibition of the B.1 wild-type (WT), delta and omicron BA.1 and BA.2 lineages by post-infusion sera from 40 individuals treated with bamlanivimab/etesevimab (BAM/ETE), casirivimab/imdevimab (CAS/IMD), and sotrovimab (SOT) as well as the activity of remdesivir, nirmatrelvir and molnupiravir. mAbs and drug activity were defined as the serum dilution (ID₅₀) and drug concentration (IC₅₀), respectively, showing 50% protection of virus-induced cytopathic effect. All pre-infusion sera were negative for SARS-CoV-2 neutralizing activity. BAM/ETE, CAS/IMD, and SOT showed activity against the WT (ID₅₀ 6295 (4355–8075) for BAM/ETE; 18,214 (16,248–21,365) for CAS/IMD; and 456 (265–592) for SOT) and the delta (14,780 (ID₅₀ 10,905–21,020) for BAM/ETE; 63,937 (47,211–79,971) for CAS/IMD; and 1103 (843–1334) for SOT). Notably, only SOT was active against BA.1 (ID₅₀ 200 (37–233)), whereas BA.2 was neutralized by CAS/IMD (ID₅₀ 174 (134–209) ID₅₀) and SOT (ID₅₀ 20 (9–31) ID₅₀), but not by BAM/ETE. No significant inter-variant IC₅₀ differences were observed for molnupiravir (1.5 ± 0.1/1.5 ± 0.7/1.0 ± 0.5/0.8 ± 0.01 μM for WT/delta/BA.1/BA.2, respectively), nirmatrelvir (0.05 ± 0.02/0.06 ± 0.01/0.04 ± 0.02/0.04 ± 0.01 μM) or remdesivir (0.08 ± 0.04/0.11 ± 0.08/0.05 ± 0.04/0.08 ± 0.01 μM). Continued evolution of SARS-CoV-2 requires updating the mAbs arsenal, although antivirals have so far remained unaffected.
    Keywords Severe acute respiratory syndrome coronavirus 2 ; antiviral agents ; blood serum ; cytopathogenicity ; evolution ; viruses
    Language English
    Dates of publication 2022-0623
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2516098-9
    ISSN 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14071374
    Database NAL-Catalogue (AGRICOLA)

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  7. Article: SARS-CoV-2 Neutralizing Antibodies to B.1 and to BA.5 Variant after Booster Dose of BNT162b2 Vaccine in HIV Patients COVID-Naïve and on Successful Antiretroviral Therapy.

    Vicenti, Ilaria / Basso, Monica / Pirola, Nicole / Bragato, Beatrice / Rossi, Maria Cristina / Giobbia, Mario / Pascoli, Susanna / Vinci, Antonio / Caputo, Sara / Varasi, Ilenia / Biba, Camilla / Fiaschi, Lia / Zazzi, Maurizio / Parisi, Saverio Giuseppe

    Vaccines

    2023  Volume 11, Issue 4

    Abstract: Live virus neutralization is the gold standard to investigate immunity. This prospective observational study aimed to determine the magnitude of response against the original B.1 lineage and against the BA.5 lineage six months after the third BNT162b2 ... ...

    Abstract Live virus neutralization is the gold standard to investigate immunity. This prospective observational study aimed to determine the magnitude of response against the original B.1 lineage and against the BA.5 lineage six months after the third BNT162b2 mRNA vaccine dose in patients with HIV infection on successful antiretroviral treatment and no previous SARS-CoV-2 infection. A total of 100 subjects (M/F 83/17, median age 54 years) were included in the analysis: 95 had plasma HIV RNA <40 copies/mL, the median CD4+ T cell count at the administration of the third dose was 580 cells/mm
    Language English
    Publishing date 2023-04-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines11040871
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Neutralizing antibodies response to novel SARS-CoV-2 omicron sublineages in long-term care facility residents after the fourth dose of monovalent BNT162b2 COVID-19 vaccination.

    Varasi, Ilenia / Lai, Alessia / Fiaschi, Lia / Bergna, Annalisa / Gatti, Antonella / Caimi, Barbara / Biba, Camilla / Della Ventura, Carla / Balotta, Claudia / Riva, Agostino / Zehender, Gianguglielmo / Zazzi, Maurizio / Vicenti, Ilaria

    The Journal of infection

    2023  Volume 87, Issue 3, Page(s) 270–272

    MeSH term(s) Humans ; BNT162 Vaccine ; COVID-19/prevention & control ; COVID-19 Vaccines ; Long-Term Care ; SARS-CoV-2 ; Antibodies, Viral ; Vaccination
    Chemical Substances BNT162 Vaccine ; COVID-19 Vaccines ; Antibodies, Viral
    Language English
    Publishing date 2023-06-30
    Publishing country England
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 424417-5
    ISSN 1532-2742 ; 0163-4453
    ISSN (online) 1532-2742
    ISSN 0163-4453
    DOI 10.1016/j.jinf.2023.06.019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Efficacy of Licensed Monoclonal Antibodies and Antiviral Agents against the SARS-CoV-2 Omicron Sublineages BA.1 and BA.2.

    Fiaschi, Lia / Dragoni, Filippo / Schiaroli, Elisabetta / Bergna, Annalisa / Rossetti, Barbara / Giammarino, Federica / Biba, Camilla / Gidari, Anna / Lai, Alessia / Nencioni, Cesira / Francisci, Daniela / Zazzi, Maurizio / Vicenti, Ilaria

    Viruses

    2022  Volume 14, Issue 7

    Abstract: Newly emerging SARS-CoV-2 variants may escape monoclonal antibodies (mAbs) and antiviral drugs. By using live virus assays, we assessed the ex vivo inhibition of the B.1 wild-type (WT), delta and omicron BA.1 and BA.2 lineages by post-infusion sera from ... ...

    Abstract Newly emerging SARS-CoV-2 variants may escape monoclonal antibodies (mAbs) and antiviral drugs. By using live virus assays, we assessed the ex vivo inhibition of the B.1 wild-type (WT), delta and omicron BA.1 and BA.2 lineages by post-infusion sera from 40 individuals treated with bamlanivimab/etesevimab (BAM/ETE), casirivimab/imdevimab (CAS/IMD), and sotrovimab (SOT) as well as the activity of remdesivir, nirmatrelvir and molnupiravir. mAbs and drug activity were defined as the serum dilution (ID
    MeSH term(s) Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized ; Antibodies, Neutralizing ; Antibodies, Viral ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; COVID-19/drug therapy ; Humans ; Membrane Glycoproteins ; Neutralization Tests ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Viral Envelope Proteins
    Chemical Substances Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Antibodies, Neutralizing ; Antibodies, Viral ; Antiviral Agents ; Membrane Glycoproteins ; Spike Glycoprotein, Coronavirus ; Viral Envelope Proteins ; spike protein, SARS-CoV-2 ; sotrovimab (1MTK0BPN8V) ; imdevimab (2Z3DQD2JHM) ; bamlanivimab (45I6OFJ8QH) ; casirivimab (J0FI6WE1QN) ; etesevimab (N7Q9NLF11I)
    Language English
    Publishing date 2022-06-23
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14071374
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Long-Term Longitudinal Analysis of Neutralizing Antibody Response to Three Vaccine Doses in a Real-Life Setting of Previously SARS-CoV-2 Infected Healthcare Workers: A Model for Predicting Response to Further Vaccine Doses.

    Parisi, Saverio Giuseppe / Mengoli, Carlo / Basso, Monica / Vicenti, Ilaria / Gatti, Francesca / Scaggiante, Renzo / Fiaschi, Lia / Giammarino, Federica / Iannetta, Marco / Malagnino, Vincenzo / Zago, Daniela / Dragoni, Filippo / Zazzi, Maurizio

    Vaccines

    2022  Volume 10, Issue 8

    Abstract: We report the time course of neutralizing antibody (NtAb) response, as measured by authentic virus neutralization, in healthcare workers (HCWs) with a mild or asymptomatic SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection diagnosed ... ...

    Abstract We report the time course of neutralizing antibody (NtAb) response, as measured by authentic virus neutralization, in healthcare workers (HCWs) with a mild or asymptomatic SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection diagnosed at the onset of the pandemic, with no reinfection throughout and after a three-dose schedule of the BNT162b2 mRNA vaccine with an overall follow-up of almost two years since infection. Forty-eight HCWs (median age 47 years, all immunocompetent) were evaluated: 29 (60.4%) were asymptomatic. NtAb serum was titrated at eight subsequent time points: T1 and T2 were after natural infection, T3 on the day of the first vaccine dose, T4 on the day of the second dose, T5, T6, and T7 were between the second and third dose, and T8 followed the third dose by a median of 34 days. NtAb titers at all postvaccination time points (T4 to T8) were significantly higher than all those at prevaccination time points (T1 to T3). The highest NtAb increase was following the first vaccine dose while subsequent doses did not further boost NtAb titers. However, the third vaccine dose appeared to revive waning immunity. NtAb levels were positively correlated at most time points suggesting an important role for immunogenetics.
    Language English
    Publishing date 2022-08-02
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines10081237
    Database MEDical Literature Analysis and Retrieval System OnLINE

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