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Prof. Dr. Stefano Aquaro
Department of Pharmacy, Health, and Nutritional Sciences; University of Calabria; Italy

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0 antivirals
0 mechanisms of virus entry
0 Virus Evolution
0 NeuroAIDS

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Journal article
Published: 18 June 2021 in Applied Sciences
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Transition metal complexes are attracting attention because of their various chemical and biological properties. In particular, the NHC-gold complexes represent a productive field of research in medicinal chemistry, mostly as anticancer tools, displaying a broad range of targets. In addition to the already known biological targets, recently, an important activity in the organization of the cell cytoskeleton was discovered. In this paper, we demonstrated that two NHC-gold complexes (namely AuL4 and AuL7) possessing good anticancer activity and multi-target properties, as stated in our previous studies, play a major role in regulating the actin polymerization, by the means of in silico and in vitro assays. Using immunofluorescence and direct enzymatic assays, we proved that both the complexes inhibited the actin polymerization reaction without promoting the depolymerization of actin filaments. Our outcomes may contribute toward deepening the knowledge of NHC-gold complexes, with the objective of producing more effective and safer drugs for treating cancer diseases.

ACS Style

Domenico Iacopetta; Jessica Ceramella; Camillo Rosano; Annaluisa Mariconda; Michele Pellegrino; Marco Sirignano; Carmela Saturnino; Alessia Catalano; Stefano Aquaro; Pasquale Longo; Maria Sinicropi. N-Heterocyclic Carbene-Gold(I) Complexes Targeting Actin Polymerization. Applied Sciences 2021, 11, 5626 .

AMA Style

Domenico Iacopetta, Jessica Ceramella, Camillo Rosano, Annaluisa Mariconda, Michele Pellegrino, Marco Sirignano, Carmela Saturnino, Alessia Catalano, Stefano Aquaro, Pasquale Longo, Maria Sinicropi. N-Heterocyclic Carbene-Gold(I) Complexes Targeting Actin Polymerization. Applied Sciences. 2021; 11 (12):5626.

Chicago/Turabian Style

Domenico Iacopetta; Jessica Ceramella; Camillo Rosano; Annaluisa Mariconda; Michele Pellegrino; Marco Sirignano; Carmela Saturnino; Alessia Catalano; Stefano Aquaro; Pasquale Longo; Maria Sinicropi. 2021. "N-Heterocyclic Carbene-Gold(I) Complexes Targeting Actin Polymerization." Applied Sciences 11, no. 12: 5626.

Review
Published: 19 January 2021 in Antibiotics
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Antimicrobials have allowed medical advancements over several decades. However, the continuous emergence of antimicrobial resistance restricts efficacy in treating infectious diseases. In this context, the drug repositioning of already known biological active compounds to antimicrobials could represent a useful strategy. In 2002 and 2003, the SARS-CoV pandemic immobilized the Far East regions. However, the drug discovery attempts to study the virus have stopped after the crisis declined. Today’s COVID-19 pandemic could probably have been avoided if those efforts against SARS-CoV had continued. Recently, a new coronavirus variant was identified in the UK. Because of this, the search for safe and potent antimicrobials and antivirals is urgent. Apart from antiviral treatment for severe cases of COVID-19, many patients with mild disease without pneumonia or moderate disease with pneumonia have received different classes of antibiotics. Diarylureas are tyrosine kinase inhibitors well known in the art as anticancer agents, which might be useful tools for a reposition as antimicrobials. The first to come onto the market as anticancer was sorafenib, followed by some other active molecules. For this interesting class of organic compounds antimicrobial, antiviral, antithrombotic, antimalarial, and anti-inflammatory properties have been reported in the literature. These numerous properties make these compounds interesting for a new possible pandemic considering that, as well as for other viral infections also for CoVID-19, a multitarget therapeutic strategy could be favorable. This review is meant to be an overview on diarylureas, focusing on their biological activities, not dwelling on the already known antitumor activity. Quite a lot of papers present in the literature underline and highlight the importance of these molecules as versatile scaffolds for the development of new and promising antimicrobials and multitarget agents against new pandemic events.

ACS Style

Alessia Catalano; Domenico Iacopetta; Michele Pellegrino; Stefano Aquaro; Carlo Franchini; Maria Sinicropi. Diarylureas: Repositioning from Antitumor to Antimicrobials or Multi-Target Agents against New Pandemics. Antibiotics 2021, 10, 92 .

AMA Style

Alessia Catalano, Domenico Iacopetta, Michele Pellegrino, Stefano Aquaro, Carlo Franchini, Maria Sinicropi. Diarylureas: Repositioning from Antitumor to Antimicrobials or Multi-Target Agents against New Pandemics. Antibiotics. 2021; 10 (1):92.

Chicago/Turabian Style

Alessia Catalano; Domenico Iacopetta; Michele Pellegrino; Stefano Aquaro; Carlo Franchini; Maria Sinicropi. 2021. "Diarylureas: Repositioning from Antitumor to Antimicrobials or Multi-Target Agents against New Pandemics." Antibiotics 10, no. 1: 92.

Journal article
Published: 23 February 2020 in Viruses
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Immune-suppression driven Hepatitis B Virus (HBV)-reactivation poses serious concerns since it occurs in several clinical settings and can result in severe forms of hepatitis. Previous studies showed that HBV strains, circulating in patients with HBV-reactivation, are characterized by an enrichment of immune-escape mutations in HBV surface antigen (HBsAg). Here, we focused on specific immune-escape mutations associated with the acquisition of N-linked glycosylation sites in HBsAg (NLGSs). In particular, we investigated profiles of NLGSs in 47 patients with immunosuppression-driven HBV-reactivation and we evaluated their impact on HBsAg-antigenicity and HBV-replication in vitro. At HBV-reactivation, despite a median serum HBV-DNA of 6.7 [5.3–8.0] logIU/mL, 23.4% of patients remained HBsAg-negative. HBsAg-negativity at HBV-reactivation correlated with the presence of >1 additional NLGSs (p < 0.001). These NLGSs are located in the major hydrophilic region of HBsAg (known to be the target of antibodies) and resulted from the single mutation T115N, T117N, T123N, N114ins, and from the triple mutant S113N+T131N+M133T. In vitro, NLGSs strongly alter HBsAg antigenic properties and recognition by antibodies used in assays for HBsAg-quantification without affecting HBsAg-secretion and other parameters of HBV-replication. In conclusion, additional NLGSs correlate with HBsAg-negativity despite HBV-reactivation, and hamper HBsAg-antigenicity in vitro, supporting the role of NGSs in immune-escape and the importance of HBV-DNA for a proper diagnosis of HBV-reactivation.

ACS Style

Romina Salpini; Lorenzo Piermatteo; Arianna Battisti; Luna Colagrossi; Marianna Aragri; Katia Yu La Rosa; Ada Bertoli; Patrizia Saccomandi; Miriam Lichtner; Massimo Marignani; Sarah Maylin; Constance Delaugerre; Filomena Morisco; Nicola Coppola; Aldo Marrone; Nerio Iapadre; Carlotta Cerva; Stefano Aquaro; Mario Angelico; Loredana Sarmati; Massimo Andreoni; Jens Verheyen; Francesca Ceccherini-Silberstein; Massimo Levrero; Carlo Federico Perno; Laura Belloni; Valentina Svicher. A Hyper-Glycosylation of HBV Surface Antigen Correlates with HBsAg-Negativity at Immunosuppression-Driven HBV Reactivation in Vivo and Hinders HBsAg Recognition In Vitro. Viruses 2020, 12, 251 .

AMA Style

Romina Salpini, Lorenzo Piermatteo, Arianna Battisti, Luna Colagrossi, Marianna Aragri, Katia Yu La Rosa, Ada Bertoli, Patrizia Saccomandi, Miriam Lichtner, Massimo Marignani, Sarah Maylin, Constance Delaugerre, Filomena Morisco, Nicola Coppola, Aldo Marrone, Nerio Iapadre, Carlotta Cerva, Stefano Aquaro, Mario Angelico, Loredana Sarmati, Massimo Andreoni, Jens Verheyen, Francesca Ceccherini-Silberstein, Massimo Levrero, Carlo Federico Perno, Laura Belloni, Valentina Svicher. A Hyper-Glycosylation of HBV Surface Antigen Correlates with HBsAg-Negativity at Immunosuppression-Driven HBV Reactivation in Vivo and Hinders HBsAg Recognition In Vitro. Viruses. 2020; 12 (2):251.

Chicago/Turabian Style

Romina Salpini; Lorenzo Piermatteo; Arianna Battisti; Luna Colagrossi; Marianna Aragri; Katia Yu La Rosa; Ada Bertoli; Patrizia Saccomandi; Miriam Lichtner; Massimo Marignani; Sarah Maylin; Constance Delaugerre; Filomena Morisco; Nicola Coppola; Aldo Marrone; Nerio Iapadre; Carlotta Cerva; Stefano Aquaro; Mario Angelico; Loredana Sarmati; Massimo Andreoni; Jens Verheyen; Francesca Ceccherini-Silberstein; Massimo Levrero; Carlo Federico Perno; Laura Belloni; Valentina Svicher. 2020. "A Hyper-Glycosylation of HBV Surface Antigen Correlates with HBsAg-Negativity at Immunosuppression-Driven HBV Reactivation in Vivo and Hinders HBsAg Recognition In Vitro." Viruses 12, no. 2: 251.

Review article
Published: 01 January 2020 in Virulence
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Ongoing with current combinations of antiretroviral drugs for the treatment of Human Immunodeficiency Virus (HIV) infection can successfully maintain long-term suppression of HIV-1 replication in plasma. Still, none of these therapies is capable of extinguishing the virus from the long-lived cellular reservoir, including monocyte-derived macrophages (MDM), that means the principal obstacle to HIV cure. MDM are widely distributed in all tissues and organs, including central system nervous (CNS) where they represent the most frequent HIV-infected cells that means the principal obstacle to HIV cure. Current FDA-approved antiretroviral drugs target viral reverse transcriptase, protease, integrase, and entry processes (coreceptor or fusion blockade). It is desirable to continue to develop new antiretrovirals directed against alternative targets in the virus lifecycle in order to further optimize therapeutic options, overcome resistance to existing medications, and potentially contribute to the elimination of viral reservoirs. This review provides a comprehensive overview of the activity of antiretroviral drugs (classical and upcoming) in monocytes-derived macrophages (MDM). Defining the antiviral activity of these drugs in this important cellular HIV-1 reservoir provides crucial hints about their efficacy in HIV-1 infected patients.

ACS Style

Stefano Aquaro; Ana Borrajo; Michele Pellegrino; Valentina Svicher. Mechanisms underlying of antiretroviral drugs in different cellular reservoirs with a focus on macrophages. Virulence 2020, 11, 400 -413.

AMA Style

Stefano Aquaro, Ana Borrajo, Michele Pellegrino, Valentina Svicher. Mechanisms underlying of antiretroviral drugs in different cellular reservoirs with a focus on macrophages. Virulence. 2020; 11 (1):400-413.

Chicago/Turabian Style

Stefano Aquaro; Ana Borrajo; Michele Pellegrino; Valentina Svicher. 2020. "Mechanisms underlying of antiretroviral drugs in different cellular reservoirs with a focus on macrophages." Virulence 11, no. 1: 400-413.

Journal article
Published: 21 June 2019 in Medicina
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Background and objectives: To enter the target cell, HIV-1 binds not only CD4 but also a co-receptor β-chemokine receptor 5 (CCR5) or α chemokine receptor 4 (CXCR4). Limited information is available on the impact of co-receptor usage on HIV-1 replication in monocyte-derived macrophages (MDM) and on the homeostasis of this important cellular reservoir. Materials and Methods: Replication (measured by p24 production) of the CCR5-tropic 81A strain increased up to 10 days post-infection and then reached a plateau. Conversely, the replication of the CXCR4-tropic NL4.3 strain (after an initial increase up to day 7) underwent a drastic decrease becoming almost undetectable after 10 days post-infection. The ability of CCR5-tropic and CXCR4-tropic strains to induce cell death in MDM was then evaluated. While for CCR5-tropic 81A the rate of apoptosis in MDM was comparable to uninfected MDM, the infection of CXCR4-tropic NL4.3 in MDM was associated with a rate of 14.3% of apoptotic cells at day 6 reaching a peak of 43.5% at day 10 post-infection. Results: This suggests that the decrease in CXCR4-tropic strain replication in MDM can be due to their ability to induce cell death in MDM. The increase in apoptosis was paralleled with a 2-fold increase in the phosphorylated form of p38 compared to WT. Furthermore, microarray analysis showed modulation of proapoptotic and cancer-related genes induced by CXCR4-tropic strains starting from 24 h after infection, whereas CCR5 viruses modulated the expression of genes not correlated with apoptotic-pathways. Conclusions: In conclusion, CXCR4-tropic strains can induce a remarkable depletion of MDM. Conversely, MDM can represent an important cellular reservoir for CCR5-tropic strains supporting the role of CCR5-usage in HIV-1 pathogenesis and as a pharmacological target to contribute to an HIV-1 cure.

ACS Style

Ana Borrajo; Alessandro Ranazzi; Michela Pollicita; Maria Concetta Bellocchi; Romina Salpini; Maria Vittoria Mauro; Francesca Ceccherini-Silberstein; Carlo Federico Perno; Valentina Svicher; Stefano Aquaro. Different Patterns of HIV-1 Replication in MACROPHAGES is Led by Co-Receptor Usage. Medicina 2019, 55, 297 .

AMA Style

Ana Borrajo, Alessandro Ranazzi, Michela Pollicita, Maria Concetta Bellocchi, Romina Salpini, Maria Vittoria Mauro, Francesca Ceccherini-Silberstein, Carlo Federico Perno, Valentina Svicher, Stefano Aquaro. Different Patterns of HIV-1 Replication in MACROPHAGES is Led by Co-Receptor Usage. Medicina. 2019; 55 (6):297.

Chicago/Turabian Style

Ana Borrajo; Alessandro Ranazzi; Michela Pollicita; Maria Concetta Bellocchi; Romina Salpini; Maria Vittoria Mauro; Francesca Ceccherini-Silberstein; Carlo Federico Perno; Valentina Svicher; Stefano Aquaro. 2019. "Different Patterns of HIV-1 Replication in MACROPHAGES is Led by Co-Receptor Usage." Medicina 55, no. 6: 297.

Review
Published: 17 May 2019 in Molecules
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Viruses represent the most common cause of infectious diseases worldwide and those with rapid propagation and high infection rates cause human and animal pandemics. These fast-spreading diseases are generally treated with antiviral drugs but, often, drug resistance occurs because of the ability of the pathogens to mutate rapidly and become less susceptible to the treatments. Even though new antivirals have been approved, e.g., in HIV (human immunodeficiency virus) and HCV (hepatitis C virus) therapeutic areas, the need to dispose of new pharmaceutical tools for the management of infections that still have no treatment is of growing interest. In these areas, carbazole represents an important privileged scaffold in drug discovery. Many compounds with a carbazolic core have been developed and some of them have shown antiviral activity. This review provides an overview on some already known carbazole derivatives, pointing the attention on the running progresses in identifying new molecules with carbazolic structure, that have shown interesting and encouraging in vitro and in vivo properties. These drugs may be exploited as valid alternatives in antiviral therapy.

ACS Style

Anna Caruso; Jessica Ceramella; Domenico Iacopetta; Carmela Saturnino; Maria Vittoria Mauro; Rosalinda Bruno; Stefano Aquaro; Maria Stefania Sinicropi. Carbazole Derivatives as Antiviral Agents: An Overview. Molecules 2019, 24, 1912 .

AMA Style

Anna Caruso, Jessica Ceramella, Domenico Iacopetta, Carmela Saturnino, Maria Vittoria Mauro, Rosalinda Bruno, Stefano Aquaro, Maria Stefania Sinicropi. Carbazole Derivatives as Antiviral Agents: An Overview. Molecules. 2019; 24 (10):1912.

Chicago/Turabian Style

Anna Caruso; Jessica Ceramella; Domenico Iacopetta; Carmela Saturnino; Maria Vittoria Mauro; Rosalinda Bruno; Stefano Aquaro; Maria Stefania Sinicropi. 2019. "Carbazole Derivatives as Antiviral Agents: An Overview." Molecules 24, no. 10: 1912.

Review
Published: 02 February 2019 in Molecules
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HIV entry in the host cell requires the interaction with the CD4 membrane receptor, and depends on the activation of one or both co-receptors CCR5 and CXCR4. Former selective co-receptor antagonists, acting at early stages of infection, are able to impair the receptor functions, preventing the viral spread toward AIDS. Due to the capability of HIV to develop resistance by switching from CCR5 to CXCR4, dual co-receptor antagonists could represent the next generation of AIDS prophylaxis drugs. We herein present a survey on relevant results published in the last few years on compounds acting simultaneously on both co-receptors, potentially useful as preventing agents or in combination with classical anti-retroviral drugs based therapy.

ACS Style

Fedora Grande; Maria Antonietta Occhiuzzi; Bruno Rizzuti; Giuseppina Ioele; Michele De Luca; Paola Tucci; Valentina Svicher; Stefano Aquaro; Antonio Garofalo. CCR5/CXCR4 Dual Antagonism for the Improvement of HIV Infection Therapy. Molecules 2019, 24, 550 .

AMA Style

Fedora Grande, Maria Antonietta Occhiuzzi, Bruno Rizzuti, Giuseppina Ioele, Michele De Luca, Paola Tucci, Valentina Svicher, Stefano Aquaro, Antonio Garofalo. CCR5/CXCR4 Dual Antagonism for the Improvement of HIV Infection Therapy. Molecules. 2019; 24 (3):550.

Chicago/Turabian Style

Fedora Grande; Maria Antonietta Occhiuzzi; Bruno Rizzuti; Giuseppina Ioele; Michele De Luca; Paola Tucci; Valentina Svicher; Stefano Aquaro; Antonio Garofalo. 2019. "CCR5/CXCR4 Dual Antagonism for the Improvement of HIV Infection Therapy." Molecules 24, no. 3: 550.

Journal article
Published: 26 October 2018 in Antiviral Research
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To compare the kinetics of integration, p24 production and equilibrium of the different HIV-DNA forms in human primary cells in the presence/absence of integrase-inhibitors (INIs) in vitro. Monocyte-derived-macrophages (MDMs), CD4+ T-cells and peripheral blood mononuclear cells (PBMCs) were infected with HIV-1 in the presence/absence of raltegravir and dolutegravir. HIV-DNA levels and p24 production were measured by qPCR and ELISA assays, respectively. In the absence of INIs, levels of HIV-DNA forms were initially very low, with an increase in the integration process starting at 3 dpi. HIV-DNA increased more slowly in MDMs than it did in CD4+ T-cells and PMBCs peaking at 21 dpi with a mean of 1580 (±890) and 615 (±37) copies/103 cells for proviral and unintegrated HIV-DNA, and 455,972 (±213,255) pg/mL of p24 at the same time point. In CD4+ T-cells the proviral HIV-DNA increased together with unintegrated HIV-DNA peaking at 7 dpi (583 ± 261 and 338 ± 254 copies/103 cells) when the p24 was 218,000 (±75,600) pg/mL. A similar trend was observed in PBMCs (494 ± 361 and 350 ± 123 copies/103 cells for proviral and unintegrated HIV-DNA, and p24 production of 149,400 ± 131,800 pg/mL). Both INIs inhibited viral replication and integration in all the cell types that were tested, especially starting at 3 dpi. However, a small but measurable amount of HIV-DNA (<5 copies/103 cells) was still observed in treated-MDMs up to 30 dpi. In conclusion, our study showed differences in HIV-DNA kinetic integration between CD4+ T-cells and MDMs, which could explain the divergent kinetics of viral-replication. Both INIs inhibited HIV-1 integration and replication with no difference found between CD4+ T-cells and MDMs. However, residual HIV-DNA remained detectable up to 30 dpi in INI-treated MDMs although complete inhibition of HIV replication was achieved. The clinical significance of this minor DNA persistence deserves further investigation considering the role of macrophages as reservoirs.

ACS Style

Matteo Surdo; Maria Francesca Cortese; Chiara Orlandi; Fabiola Di Santo; Stefano Aquaro; Mauro Magnani; Carlo Federico Perno; Anna Casabianca; Francesca Ceccherini-Silberstein. Different kinetics of viral replication and DNA integration in the main HIV-1 cellular reservoirs in the presence and absence of integrase inhibitors. Antiviral Research 2018, 160, 165 -174.

AMA Style

Matteo Surdo, Maria Francesca Cortese, Chiara Orlandi, Fabiola Di Santo, Stefano Aquaro, Mauro Magnani, Carlo Federico Perno, Anna Casabianca, Francesca Ceccherini-Silberstein. Different kinetics of viral replication and DNA integration in the main HIV-1 cellular reservoirs in the presence and absence of integrase inhibitors. Antiviral Research. 2018; 160 ():165-174.

Chicago/Turabian Style

Matteo Surdo; Maria Francesca Cortese; Chiara Orlandi; Fabiola Di Santo; Stefano Aquaro; Mauro Magnani; Carlo Federico Perno; Anna Casabianca; Francesca Ceccherini-Silberstein. 2018. "Different kinetics of viral replication and DNA integration in the main HIV-1 cellular reservoirs in the presence and absence of integrase inhibitors." Antiviral Research 160, no. : 165-174.

Article
Published: 17 May 2018 in Virus Genes
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The aim of this study is to evaluate the amino acid variability of HIV-1 Gp41, C2–V3, and Nef in a group of patients characterized by different disease progression rates. HIV-1 sequences were collected from 19 Long term non progressor patients (LTNPs), 9 slow progressors (SPs), and 11 rapid progressors (RPs). Phylogenetic trees were estimated by MEGA 6. Differences in amino acid variability among sequences belonging to the 3 groups have been evaluated by amino acid divergence, Shannon entropy analysis, and the number of amino acid mutations (defined as amino acid variations compared with HxB2). The involvement of amino acid mutations on epitope rich regions was also investigated. The population was mainly composed of males (74.3%) and HIV-1 subtype B strains (B: 92.32%, CRF_12BF, A1, C: 2.56% each). Viral load (log10 copies/mL) and CD4+T cell count (cells/mm3) were 3.9 (3.5–4.2) and 618 (504–857) in LTNPs, 3.3 (2.8–4.7) and 463 (333–627) in SPs, and 4.6 (4.3–5.3) and 201 (110–254) in RPs. Gp41 and C2–V3 amino acid divergence was lower in LTNP and SP strains compared to RPs (median value: 0.085 and 0.091 vs. 0.114, p = 0.005 and 0.042) and a trend of lower variability was observed for Nef (p = 0.198). A lower entropy value was observed at 10, 3, and 7 positions of Gp41, C2–V3, and Nef belonging to LTNPs and at 7, 3, and 1 positions of Gp41, C2–V3, and Nef belonging to SPs compared with RPs (p < 0.05). Focusing on epitope rich regions, again a higher degree of conservation was observed in Gp41 and C2–V3 sequences belonging to LTNPs and SPs compared to those belonging to RPs. This study shows that the extent of amino acid variability correlates with a different HIV-1 progression rate. This variability also involves CTL epitope rich regions, thus suggesting its involvement in the immune escape process modulation.

ACS Style

Rossana Scutari; Monica Faieta; Roberta D’Arrigo; Lavinia Fabeni; Cristina Mussini; Andrea Cossarizza; Claudio Casoli; Carlo Federico Perno; Valentina Svicher; Claudia Alteri; Stefano Aquaro. The degree of HIV-1 amino acid variability is strictly related to different disease progression rates. Virus Genes 2018, 54, 493 -501.

AMA Style

Rossana Scutari, Monica Faieta, Roberta D’Arrigo, Lavinia Fabeni, Cristina Mussini, Andrea Cossarizza, Claudio Casoli, Carlo Federico Perno, Valentina Svicher, Claudia Alteri, Stefano Aquaro. The degree of HIV-1 amino acid variability is strictly related to different disease progression rates. Virus Genes. 2018; 54 (4):493-501.

Chicago/Turabian Style

Rossana Scutari; Monica Faieta; Roberta D’Arrigo; Lavinia Fabeni; Cristina Mussini; Andrea Cossarizza; Claudio Casoli; Carlo Federico Perno; Valentina Svicher; Claudia Alteri; Stefano Aquaro. 2018. "The degree of HIV-1 amino acid variability is strictly related to different disease progression rates." Virus Genes 54, no. 4: 493-501.

Communication
Published: 30 January 2018 in Molecules
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Background: Despite the progress achieved by anti-retroviral drug research in the last decades, the discovery of novel compounds endowed with selective antiviral activity and reduced side effects is still a necessity. At present, the most urgent requirement includes the improvement of HIV (Human Immunodeficiency Virus) prevention and sexual transmission and the development of new drugs to treat the chronic lifelong infection. Methods: Six chloro-1,4-dimethyl-9H-carbazoles (2a,b–4a,b) have been prepared following opportunely modified known chemical procedures and tested in luciferase and Escherichia coli β-galactosidase expressing CD4+, CXCR4+, CCR5+ TZM-bl cells. Results and Conclusion: a preliminary biological investigation on the synthesized small series of chloro-1,4-dimethyl-9H-carbazoles has been carried out. Among all tested compounds, a nitro-derivative (3b) showed the most interesting profile representing a suitable lead for the development of novel anti-HIV drugs.

ACS Style

Carmela Saturnino; Fedora Grande; Stefano Aquaro; Anna Caruso; Domenico Iacopetta; Maria Grazia Bonomo; Pasquale Longo; Dominique Schols; Maria Stefania Sinicropi. Chloro-1,4-dimethyl-9H-carbazole Derivatives Displaying Anti-HIV Activity. Molecules 2018, 23, 286 .

AMA Style

Carmela Saturnino, Fedora Grande, Stefano Aquaro, Anna Caruso, Domenico Iacopetta, Maria Grazia Bonomo, Pasquale Longo, Dominique Schols, Maria Stefania Sinicropi. Chloro-1,4-dimethyl-9H-carbazole Derivatives Displaying Anti-HIV Activity. Molecules. 2018; 23 (2):286.

Chicago/Turabian Style

Carmela Saturnino; Fedora Grande; Stefano Aquaro; Anna Caruso; Domenico Iacopetta; Maria Grazia Bonomo; Pasquale Longo; Dominique Schols; Maria Stefania Sinicropi. 2018. "Chloro-1,4-dimethyl-9H-carbazole Derivatives Displaying Anti-HIV Activity." Molecules 23, no. 2: 286.

Journal article
Published: 28 September 2017 in Viruses
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A paucity of information is available on the activity of protease inhibitors (PI) in chronically-infected monocyte-derived macrophages (MDM) and on the kinetics of viral-rebound after PI removal in vitro. To fill this gap, the activity of different concentrations of amprenavir (AMP) was evaluated in chronically-infected MDM by measuring p24-production every day up to 12 days after drug administration and up to seven days after drug removal. Clinically-relevant concentrations of AMP (4 and 20 μM) drastically decreased p24 amount released from chronically-infected MDM from Day 2 up to Day 12 after drug administration. The kinetics of viral-rebound after AMP-removal (4 and 20 μM) showed that, despite an initial increase, p24-production over time never reached the level observed for untreated-MDM, suggesting a persistent intracellular drug activity. In line with this, after AMP-removal, human immunodeficiency virus 1 (HIV-1) infectivity and intracellular the p24/p55 ratio (reflecting virion-maturation) were remarkably lower than observed for untreated MDM. Overall, AMP shows high efficacy in blocking HIV-1 replication in chronically-infected MDM, persisting even after drug-removal. This highlights the role of protease inhibitors in preventing the establishment of this important HIV-1 reservoir, thus reducing viral-dissemination in different anatomical compartments.

ACS Style

Ana Borrajo; Alessandro Ranazzi; Michela Pollicita; Rosalinda Bruno; Andrea Modesti; Claudia Alteri; Carlo Federico Perno; Valentina Svicher; Stefano Aquaro. Effects of Amprenavir on HIV-1 Maturation, Production and Infectivity Following Drug Withdrawal in Chronically-Infected Monocytes/Macrophages. Viruses 2017, 9, 277 .

AMA Style

Ana Borrajo, Alessandro Ranazzi, Michela Pollicita, Rosalinda Bruno, Andrea Modesti, Claudia Alteri, Carlo Federico Perno, Valentina Svicher, Stefano Aquaro. Effects of Amprenavir on HIV-1 Maturation, Production and Infectivity Following Drug Withdrawal in Chronically-Infected Monocytes/Macrophages. Viruses. 2017; 9 (10):277.

Chicago/Turabian Style

Ana Borrajo; Alessandro Ranazzi; Michela Pollicita; Rosalinda Bruno; Andrea Modesti; Claudia Alteri; Carlo Federico Perno; Valentina Svicher; Stefano Aquaro. 2017. "Effects of Amprenavir on HIV-1 Maturation, Production and Infectivity Following Drug Withdrawal in Chronically-Infected Monocytes/Macrophages." Viruses 9, no. 10: 277.

Review
Published: 06 April 2017 in Brain Sciences
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The central nervous system (CNS) is a very challenging HIV-1 sanctuary, in which HIV-1 replication is established early on during acute infection and can persist despite potent antiretroviral treatments. HIV-1 infected macrophages play a pivotal role acting as vehicles for HIV-1 to spread into the brain, and can be the major contributor of an early compartmentalization. HIV-1 infection in CNS may lead to a broad spectrum of neurological syndromes, such as dementia, mild neurocognitive disorders, and asymptomatic impairment. These clinical manifestations are caused by the release of neurotoxins from infected cells (mainly macrophages), and also by several HIV-1 proteins, able to activate cell-signaling involved in the control of cellular survival and apoptosis. This review is aimed at highlighting the virological aspects associated with the onset of neurocognitive disorders and at addressing the novel therapeutic approaches to stop HIV-1 replication in this critical sanctuary.

ACS Style

Rossana Scutari; Claudia Alteri; Carlo Federico Perno; Valentina Svicher; Stefano Aquaro. The Role of HIV Infection in Neurologic Injury. Brain Sciences 2017, 7, 38 .

AMA Style

Rossana Scutari, Claudia Alteri, Carlo Federico Perno, Valentina Svicher, Stefano Aquaro. The Role of HIV Infection in Neurologic Injury. Brain Sciences. 2017; 7 (4):38.

Chicago/Turabian Style

Rossana Scutari; Claudia Alteri; Carlo Federico Perno; Valentina Svicher; Stefano Aquaro. 2017. "The Role of HIV Infection in Neurologic Injury." Brain Sciences 7, no. 4: 38.

Journals
Published: 25 August 2015 in Organic & Biomolecular Chemistry
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Newly synthesized pyridopentaazacyclopentadecanes and their transition metal complexes are shown to interact with the human chemokine receptor CXCR4, a key target for developing new therapeutic agents. The chemokine receptor CXCR4 acts as a key cell surface receptor in HIV infections, multiple forms of cancer, and various other pathologies, such as rheumatoid arthritis and asthma. Macrocyclic polyamines and their metal complexes are known to exert anti-HIV activity, many acting as HIV entry inhibitors by specifically binding to CXCR4. Three series of pyridopentaazacylopentadecanes, in which the pyridine ring is fused to zero, one, or two saturated six-membered rings, were synthesized by manganese( ii )-templated Schiff-base cyclization of triethylenetetramine with various dicarbonyl compounds. By evaluating these macrocyclic polyamines and their complexes with Mn 2+ , Cu 2+ , Fe 3+ , and Zn 2+ , we have discovered novel CXCR4-binding compounds. The MnCl 2 complex of a new pentaazacyclopentadecane with one fused carbocyclic ring ( 11 ) was found to have the greatest potency as an antagonist of the chemokine receptor CXCR4 (IC 50 : 0.014 μM), as evidenced by inhibiting binding of CXCL12 to PBMCs (peripheral blood mononuclear cells). Consequently, this compound inhibits replication of the CXCR4-using (X4) HIV-1 strain NL4-3 in the TZM-bl cell line with an IC 50 value of 0.52 μM and low cytotoxicity (CC 50 : >100 μM). In addition, 18 other compounds were evaluated for their interaction with CXCR4 via their ability to interfere with ligand chemokine binding and HIV entry and infection. Of these, the metal complexes of the two more hydrophobic series with one or two fused carbocyclic rings exhibited the greatest potency. The Zn 2+ complex 21 was among the most potent, showing that redox activity of the metal center is not associated with CXCR4 antagonist activity.

ACS Style

Sunil Hamal; Thomas D'Huys; William F. Rowley; Kurt Vermeire; Stefano Aquaro; Brian Frost; Dominique Schols; Thomas W. Bell. Metal complexes of pyridine-fused macrocyclic polyamines targeting the chemokine receptor CXCR4. Organic & Biomolecular Chemistry 2015, 13, 10517 -10526.

AMA Style

Sunil Hamal, Thomas D'Huys, William F. Rowley, Kurt Vermeire, Stefano Aquaro, Brian Frost, Dominique Schols, Thomas W. Bell. Metal complexes of pyridine-fused macrocyclic polyamines targeting the chemokine receptor CXCR4. Organic & Biomolecular Chemistry. 2015; 13 (42):10517-10526.

Chicago/Turabian Style

Sunil Hamal; Thomas D'Huys; William F. Rowley; Kurt Vermeire; Stefano Aquaro; Brian Frost; Dominique Schols; Thomas W. Bell. 2015. "Metal complexes of pyridine-fused macrocyclic polyamines targeting the chemokine receptor CXCR4." Organic & Biomolecular Chemistry 13, no. 42: 10517-10526.

Journal article
Published: 22 June 2015 in Expert Opinion on Biological Therapy
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Thymosin α-1 (Tα1) exploits a specific action on lymphoid cells and is able to induce in peripheral blood mononuclear cells (PBMCs) a strong transcriptional response. CD8 antiviral factor activity plays a role in the control or prevention of HIV-1 infection by a non-cytolytic mechanism. The ability of Tα1 to modulate the release of antiretroviral soluble factors by CD8(+) cells was investigated. Supernatants from lipopolysaccharide (LPS) stimulated CD8(+)-isolated cells treated with Tα1 were screened on in vitro infection of human monocyte-derived macrophages (MDMs) and PBMCs with HIV-1, and of PBMCs with human T lymphotropic virus 1 (HTLV-1). In CD8(+) cells, as well as in PBMCs of healthy donors as from HIV(+) individuals, a microarray analysis to assess the transcriptional response after treatment was performed. Tα1 potentiates the release, in LPS-stimulated CD8(+) cells, of soluble factors able to inhibit both in vitro HIV-1 infection of MDMs and PBMCs and in vitro HTLV-1 infection of PBMCs. A distinctive transcriptional profile was induced by Tα1 in PBMCs from HIV(+) donors. These findings suggest that Tα1 would represent a re-evaluated approach to antiretroviral therapy in combination with innovative treatments and with vaccine administration.

ACS Style

Claudia Matteucci; Antonella Minutolo,; Michela Pollicita; Emanuela Balestrieri; Sandro Grelli; Gabriella D’Ettorre; Vincenzo Vullo; Ilaria Bucci; Alessandra Luchini; Stefano Aquaro; Paola Sinibaldi-Vallebona; Beatrice Macchi; Carlo Federico Perno; Antonio Mastino; Enrico Garaci. Thymosin α 1 potentiates the release by CD8+cells of soluble factors able to inhibit HIV-1 and human T lymphotropic virus 1 infectionin vitro. Expert Opinion on Biological Therapy 2015, 15, 83 -100.

AMA Style

Claudia Matteucci, Antonella Minutolo,, Michela Pollicita, Emanuela Balestrieri, Sandro Grelli, Gabriella D’Ettorre, Vincenzo Vullo, Ilaria Bucci, Alessandra Luchini, Stefano Aquaro, Paola Sinibaldi-Vallebona, Beatrice Macchi, Carlo Federico Perno, Antonio Mastino, Enrico Garaci. Thymosin α 1 potentiates the release by CD8+cells of soluble factors able to inhibit HIV-1 and human T lymphotropic virus 1 infectionin vitro. Expert Opinion on Biological Therapy. 2015; 15 (sup1):83-100.

Chicago/Turabian Style

Claudia Matteucci; Antonella Minutolo,; Michela Pollicita; Emanuela Balestrieri; Sandro Grelli; Gabriella D’Ettorre; Vincenzo Vullo; Ilaria Bucci; Alessandra Luchini; Stefano Aquaro; Paola Sinibaldi-Vallebona; Beatrice Macchi; Carlo Federico Perno; Antonio Mastino; Enrico Garaci. 2015. "Thymosin α 1 potentiates the release by CD8+cells of soluble factors able to inhibit HIV-1 and human T lymphotropic virus 1 infectionin vitro." Expert Opinion on Biological Therapy 15, no. sup1: 83-100.

Journal article
Published: 30 April 2011 in Antiviral Research
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Dual/mixed-tropic HIV-1 strains are predominant in a significative proportion of patients, though few information is available regarding the genetic characteristics, quasispecies composition, and susceptibility against CCR5-antagonists of the primary-isolates. For this reason, we investigated in deep details, both phenotypically and genotypically, the characteristics of 54 HIV-1 primary-isolates obtained from HIV-infected patients. Tropism was assessed by multiple-cycles phenotypic-assay on U87MG-CD4(+)-CCR5(+)-/CXCR4(+)-expressing cells. In vitro selection in PBMCs of X4-tropic viral strains following maraviroc-treatment was also performed. Phenotypic-assay reported pure R5-tropic viruses in 31 (57.4%) isolates, dual/mixed-tropic viruses in 22 (40.7%), and pure X4-tropic virus in only 1 (1.8%). Among dual/mixed-tropic isolates, 12 showed a remarkably higher replication-efficacy in CCR5-expressing cells (R5(+)/X4), and 2 in CXCR4-expressing cells (R5/X4(+)). Genotypic-tropism testing showed a correlation between PSSM-scores, geno2pheno false-positive-rate, and V3-net-charge with both CCR5-usage and syncytium-inducing ability. Moreover, specific gp120- and gp41-mutations were significantly associated with tropism and/or syncytium-inducing ability. Ultra-deep V3-pyrosequencing showed the presence of a swarm of genetically distinct species with a preference for CCR5-coreceptor not only in all pure R5-isolates, but also in 6/7 R5(+)/X4-tropic isolates. In both pure-X4 and R5/X4(+)-isolates, we observed extensive prevalence of X4-using species. In vitro selection-experiments with CCR5-inhibitor maraviroc (up to 2 months) showed no-emergence of X4-tropic variants for all R5- and R5(+)/X4-isolates tested (while X4-virus remained fully-resistant). In conclusion, our study shows that dual/mixed-tropic viruses are constituted by different species, whereby those with characteristics R5(+)/X4 are genotypically and phenotypically similar to the pure-R5 isolates; thus the use of CCR5-antagonists in patients with R5(+)/X4-tropic viruses may be a therapeutic-option that deserves further investigations

ACS Style

Valentina Svicher; Emanuela Balestra; Valeria Cento; Loredana Sarmati; Luca Dori; Ina Vandenbroucke; Roberta D’Arrigo; Anna Rita Buonomini; Herwig Van Marck; Matteo Surdo; Patrizia Saccomandi; Wendy Mostmans; Jeroen Aerssens; Stefano Aquaro; Lieven J. Stuyver; Massimo Andreoni; Francesca Ceccherini-Silberstein; Carlo Federico Perno. HIV-1 dual/mixed tropic isolates show different genetic and phenotypic characteristics and response to maraviroc in vitro. Antiviral Research 2011, 90, 42 -53.

AMA Style

Valentina Svicher, Emanuela Balestra, Valeria Cento, Loredana Sarmati, Luca Dori, Ina Vandenbroucke, Roberta D’Arrigo, Anna Rita Buonomini, Herwig Van Marck, Matteo Surdo, Patrizia Saccomandi, Wendy Mostmans, Jeroen Aerssens, Stefano Aquaro, Lieven J. Stuyver, Massimo Andreoni, Francesca Ceccherini-Silberstein, Carlo Federico Perno. HIV-1 dual/mixed tropic isolates show different genetic and phenotypic characteristics and response to maraviroc in vitro. Antiviral Research. 2011; 90 (1):42-53.

Chicago/Turabian Style

Valentina Svicher; Emanuela Balestra; Valeria Cento; Loredana Sarmati; Luca Dori; Ina Vandenbroucke; Roberta D’Arrigo; Anna Rita Buonomini; Herwig Van Marck; Matteo Surdo; Patrizia Saccomandi; Wendy Mostmans; Jeroen Aerssens; Stefano Aquaro; Lieven J. Stuyver; Massimo Andreoni; Francesca Ceccherini-Silberstein; Carlo Federico Perno. 2011. "HIV-1 dual/mixed tropic isolates show different genetic and phenotypic characteristics and response to maraviroc in vitro." Antiviral Research 90, no. 1: 42-53.

Journal article
Published: 01 October 2009 in The new microbiologica
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Muhammed Babakir-Mina; Massimo Ciccozzi; Marco Ciotti; Fabio Marcuccilli; Emanuela Balestra; Salvatore Dimonte; Carlo Federico Perno; Stefano Aquaro. Phylogenetic analysis of the surface proteins of influenza A (H5N1) viruses isolated in Asian and African populations. The new microbiologica 2009, 32, 1 .

AMA Style

Muhammed Babakir-Mina, Massimo Ciccozzi, Marco Ciotti, Fabio Marcuccilli, Emanuela Balestra, Salvatore Dimonte, Carlo Federico Perno, Stefano Aquaro. Phylogenetic analysis of the surface proteins of influenza A (H5N1) viruses isolated in Asian and African populations. The new microbiologica. 2009; 32 (4):1.

Chicago/Turabian Style

Muhammed Babakir-Mina; Massimo Ciccozzi; Marco Ciotti; Fabio Marcuccilli; Emanuela Balestra; Salvatore Dimonte; Carlo Federico Perno; Stefano Aquaro. 2009. "Phylogenetic analysis of the surface proteins of influenza A (H5N1) viruses isolated in Asian and African populations." The new microbiologica 32, no. 4: 1.

Journal article
Published: 22 May 2009 in BMC Neuroscience
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Oxidative stress plays a key role in the neuropathogenesis of Human Immunodeficiency Virus-1 (HIV-1) infection causing apoptosis of astroglia cells and neurons. Recent data have shown that oxidative stress is also responsible for the acceleration of human fibroblast telomere shortening in vitro. In the present study we analyzed the potential relations occurring between free radicals formation and telomere length during HIV-1 mediated astroglial death.

ACS Style

Michela Pollicita; Carolina Muscoli; Antonella Sgura; Alberto Biasin; Teresa Granato; Laura Masuelli; Vincenzo Mollace; Caterina Tanzarella; Claudio Del Duca; Paola Rodinò; Carlo Federico Perno; Stefano Aquaro. Apoptosis and telomeres shortening related to HIV-1 induced oxidative stress in an astrocytoma cell line. BMC Neuroscience 2009, 10, 51 -51.

AMA Style

Michela Pollicita, Carolina Muscoli, Antonella Sgura, Alberto Biasin, Teresa Granato, Laura Masuelli, Vincenzo Mollace, Caterina Tanzarella, Claudio Del Duca, Paola Rodinò, Carlo Federico Perno, Stefano Aquaro. Apoptosis and telomeres shortening related to HIV-1 induced oxidative stress in an astrocytoma cell line. BMC Neuroscience. 2009; 10 (1):51-51.

Chicago/Turabian Style

Michela Pollicita; Carolina Muscoli; Antonella Sgura; Alberto Biasin; Teresa Granato; Laura Masuelli; Vincenzo Mollace; Caterina Tanzarella; Claudio Del Duca; Paola Rodinò; Carlo Federico Perno; Stefano Aquaro. 2009. "Apoptosis and telomeres shortening related to HIV-1 induced oxidative stress in an astrocytoma cell line." BMC Neuroscience 10, no. 1: 51-51.

Conference abstract
Published: 31 May 2008 in Antiviral Research
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Stefano Aquaro; Caterina Lapenta; Filippo Belardelli; Carlo-Federico Perno; Ferdinando Nicoletti. Inhibition of HIV-1 Infection in Hu–PBL–SCID Reconstituted Mice by Rapamacyn. Antiviral Research 2008, 78, A53 .

AMA Style

Stefano Aquaro, Caterina Lapenta, Filippo Belardelli, Carlo-Federico Perno, Ferdinando Nicoletti. Inhibition of HIV-1 Infection in Hu–PBL–SCID Reconstituted Mice by Rapamacyn. Antiviral Research. 2008; 78 (2):A53.

Chicago/Turabian Style

Stefano Aquaro; Caterina Lapenta; Filippo Belardelli; Carlo-Federico Perno; Ferdinando Nicoletti. 2008. "Inhibition of HIV-1 Infection in Hu–PBL–SCID Reconstituted Mice by Rapamacyn." Antiviral Research 78, no. 2: A53.

Conference abstract
Published: 31 May 2008 in Antiviral Research
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Michela Pollicita; Carolina Muscoli; Antonella Sgura; Alberto Biasin; Vincenzo Mollace; Caterina Tanzarella; Claudio Del Duca; Paola Rodinò; Carlo Federico Perno; Stefano Aquaro. NAC Reduces Apoptosis and Telomeres Shortening Subsequent to HIV-1 Exposure in an Astrocytoma Cell Line. Antiviral Research 2008, 78, A47 -A47.

AMA Style

Michela Pollicita, Carolina Muscoli, Antonella Sgura, Alberto Biasin, Vincenzo Mollace, Caterina Tanzarella, Claudio Del Duca, Paola Rodinò, Carlo Federico Perno, Stefano Aquaro. NAC Reduces Apoptosis and Telomeres Shortening Subsequent to HIV-1 Exposure in an Astrocytoma Cell Line. Antiviral Research. 2008; 78 (2):A47-A47.

Chicago/Turabian Style

Michela Pollicita; Carolina Muscoli; Antonella Sgura; Alberto Biasin; Vincenzo Mollace; Caterina Tanzarella; Claudio Del Duca; Paola Rodinò; Carlo Federico Perno; Stefano Aquaro. 2008. "NAC Reduces Apoptosis and Telomeres Shortening Subsequent to HIV-1 Exposure in an Astrocytoma Cell Line." Antiviral Research 78, no. 2: A47-A47.

Journal article
Published: 01 October 2007 in AIDS Research and Human Retroviruses
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Enfuvirtide is the first of a new class of antiretroviral drugs that inhibits HIV entry. It is a 36 amino acid synthetic peptide that mimics the HR2 region of the HIV-1 gp41, preventing the fusion of viral and cellular membranes. Up to now, enfuvirtide was designed based on the HIV-1 B-subtype gp41, and resistance mutations to the fusion inhibitor have been investigated primarily in individuals infected with this subtype. To fill the gap, we analyzed the full length gp41 protein sequence of HIV-1 non-B strains from individuals receiving enfuvirtide-containing regimens. No primary resistance to the enfuvirtide binding domain (36–45 residues) was found. Resistance mutations were detected at follow-up visits and were comparable to those described among B-subtype HIV-1-infected patients; no sequence changes were detected in crucial HR1/HR2 gp41 sites such as the cytotoxic T lymphocyte epitope, cysteine loop, ectodomain, and 5-helix interaction and binding region.

ACS Style

Roberta D'arrigo; Massimo Ciccozzi; Caterina Gori; Stefania Montieri; Stefano Aquaro; Rita Bellagamba; Evangelo Boumis; Giovanni Di Perri; Daniele Pizzi; Andrea Antinori; Giovanni Rezza; Carlo Federico Perno. gp41 Sequence Variability in HIV Type 1 Non-B Subtypes Infected Patients Undergoing Enfuvirtide Pressure. AIDS Research and Human Retroviruses 2007, 23, 1296 -1302.

AMA Style

Roberta D'arrigo, Massimo Ciccozzi, Caterina Gori, Stefania Montieri, Stefano Aquaro, Rita Bellagamba, Evangelo Boumis, Giovanni Di Perri, Daniele Pizzi, Andrea Antinori, Giovanni Rezza, Carlo Federico Perno. gp41 Sequence Variability in HIV Type 1 Non-B Subtypes Infected Patients Undergoing Enfuvirtide Pressure. AIDS Research and Human Retroviruses. 2007; 23 (10):1296-1302.

Chicago/Turabian Style

Roberta D'arrigo; Massimo Ciccozzi; Caterina Gori; Stefania Montieri; Stefano Aquaro; Rita Bellagamba; Evangelo Boumis; Giovanni Di Perri; Daniele Pizzi; Andrea Antinori; Giovanni Rezza; Carlo Federico Perno. 2007. "gp41 Sequence Variability in HIV Type 1 Non-B Subtypes Infected Patients Undergoing Enfuvirtide Pressure." AIDS Research and Human Retroviruses 23, no. 10: 1296-1302.