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Human papillomavirus is the most common viral infectious agent responsible for cancer development in humans. High-risk strains are known to induce cancer through the expression of the viral oncogenes E6 and E7, yet we have only a partial understanding of the precise mechanisms of action of these viral proteins. Here we investigated the molecular mechanism through which the oncoprotein E6 alters the Hippo-YAP/TAZ pathway to trigger YAP/TAZ induction in cancer cells. By employing E6 overexpression systems combined with protein–protein interaction studies and loss-of-function approaches, we discovered that the E6-mediated targeting of hScrib, which supports YAP/TAZ upregulation, intimately requires E6 homodimerization. We show that the self-association of E6, previously reported only in vitro, takes place in the cytoplasm and, as a dimer, E6 targets the fraction of hScrib at the cell cortex for proteasomal degradation. Thus, E6 homodimerization emerges as an important event in the mechanism of E6-mediated hScrib targeting to sustain downstream YAP/TAZ upregulation, unraveling for the first time the key role of E6 homodimerization in the context of its transforming functions and thus paving the way for the possible development of E6 dimerization inhibitors.
Lorenzo Messa; Marta Celegato; Chiara Bertagnin; Beatrice Mercorelli; Gualtiero Alvisi; Lawrence Banks; Giorgio Palù; Arianna Loregian. The Dimeric Form of HPV16 E6 Is Crucial to Drive YAP/TAZ Upregulation through the Targeting of hScrib. Cancers 2021, 13, 4083 .
AMA StyleLorenzo Messa, Marta Celegato, Chiara Bertagnin, Beatrice Mercorelli, Gualtiero Alvisi, Lawrence Banks, Giorgio Palù, Arianna Loregian. The Dimeric Form of HPV16 E6 Is Crucial to Drive YAP/TAZ Upregulation through the Targeting of hScrib. Cancers. 2021; 13 (16):4083.
Chicago/Turabian StyleLorenzo Messa; Marta Celegato; Chiara Bertagnin; Beatrice Mercorelli; Gualtiero Alvisi; Lawrence Banks; Giorgio Palù; Arianna Loregian. 2021. "The Dimeric Form of HPV16 E6 Is Crucial to Drive YAP/TAZ Upregulation through the Targeting of hScrib." Cancers 13, no. 16: 4083.
Elrashdy M. Redwan; Mohammed F. Alghamdi; Tarek Mohamed Abd El-Aziz; Parise Adadi; Alaa A.A. Aljabali; Diksha Attrish; Gajendra Kumar Azad; Wagner Baetas-Da-Cruz; Debmalya Barh; Nicolas G. Bazan; Adam M. Brufsky; Gaurav Chauhan; S.K. Sarif Hassan; Ramesh Kandimalla; Amos Lal; Kenneth Lundstrom; Yogendra Kumar Mishra; Pabitra Pal Choudhury; Giorgio Palù; Pritam K. Panda; Damiano Pizzol; Nima Rezaei; Ángel Serrano-Aroca; Samendra P. Sherchan; Murat Seyran; Kazuo Takayama; Murtaza M. Tambuwala; Bruce D. Uhal; Vladimir N. Uversky. The mechanism behind flaring/triggering of autoimmunity disorders associated with COVID-19. Autoimmunity Reviews 2021, 20, 102909 -102909.
AMA StyleElrashdy M. Redwan, Mohammed F. Alghamdi, Tarek Mohamed Abd El-Aziz, Parise Adadi, Alaa A.A. Aljabali, Diksha Attrish, Gajendra Kumar Azad, Wagner Baetas-Da-Cruz, Debmalya Barh, Nicolas G. Bazan, Adam M. Brufsky, Gaurav Chauhan, S.K. Sarif Hassan, Ramesh Kandimalla, Amos Lal, Kenneth Lundstrom, Yogendra Kumar Mishra, Pabitra Pal Choudhury, Giorgio Palù, Pritam K. Panda, Damiano Pizzol, Nima Rezaei, Ángel Serrano-Aroca, Samendra P. Sherchan, Murat Seyran, Kazuo Takayama, Murtaza M. Tambuwala, Bruce D. Uhal, Vladimir N. Uversky. The mechanism behind flaring/triggering of autoimmunity disorders associated with COVID-19. Autoimmunity Reviews. 2021; 20 (10):102909-102909.
Chicago/Turabian StyleElrashdy M. Redwan; Mohammed F. Alghamdi; Tarek Mohamed Abd El-Aziz; Parise Adadi; Alaa A.A. Aljabali; Diksha Attrish; Gajendra Kumar Azad; Wagner Baetas-Da-Cruz; Debmalya Barh; Nicolas G. Bazan; Adam M. Brufsky; Gaurav Chauhan; S.K. Sarif Hassan; Ramesh Kandimalla; Amos Lal; Kenneth Lundstrom; Yogendra Kumar Mishra; Pabitra Pal Choudhury; Giorgio Palù; Pritam K. Panda; Damiano Pizzol; Nima Rezaei; Ángel Serrano-Aroca; Samendra P. Sherchan; Murat Seyran; Kazuo Takayama; Murtaza M. Tambuwala; Bruce D. Uhal; Vladimir N. Uversky. 2021. "The mechanism behind flaring/triggering of autoimmunity disorders associated with COVID-19." Autoimmunity Reviews 20, no. 10: 102909-102909.
Two adenovirus-based vaccines, ChAdOx1 nCoV-19 and Ad26.COV2.S, and two mRNA-based vaccines, BNT162b2 and mRNA.1273, have been approved by the European Medicines Agency (EMA), and are invaluable in preventing and reducing the incidence of coronavirus disease-2019 (COVID-19). Recent reports have pointed to thrombosis with associated thrombocytopenia as an adverse effect occurring at a low frequency in some individuals after vaccination. The causes of such events may be related to SARS-CoV-2 spike protein interactions with different C-type lectin receptors, heparan sulfate proteoglycans (HSPGs) and the CD147 receptor, or to different soluble splice variants of the spike protein, adenovirus vector interactions with the CD46 receptor or platelet factor 4 antibodies. Similar findings have been reported for several viral diseases after vaccine administration. In addition, immunological mechanisms elicited by viral vectors related to cellular delivery could play a relevant role in individuals with certain genetic backgrounds. Although rare, the potential COVID-19 vaccine-induced immune thrombotic thrombocytopenia (VITT) requires immediate validation, especially in risk groups, such as the elderly, chronic smokers, and individuals with pre-existing incidences of thrombocytopenia; and if necessary, a reformulation of existing vaccines.
Kenneth Lundstrom; Debmalya Barh; Bruce Uhal; Kazuo Takayama; Alaa Aljabali; Tarek Abd El-Aziz; Amos Lal; ElRashdy Redwan; Parise Adadi; Gaurav Chauhan; Samendra Sherchan; Gajendra Azad; Nima Rezaei; Ángel Serrano-Aroca; Nicolas Bazan; Sk Hassan; Pritam Panda; Pabitra Pal Choudhury; Damiano Pizzol; Ramesh Kandimalla; Wagner Baetas-Da-Cruz; Yogendra Mishra; Giorgio Palu; Adam Brufsky; Murtaza Tambuwala; Vladimir Uversky. COVID-19 Vaccines and Thrombosis—Roadblock or Dead-End Street? Biomolecules 2021, 11, 1020 .
AMA StyleKenneth Lundstrom, Debmalya Barh, Bruce Uhal, Kazuo Takayama, Alaa Aljabali, Tarek Abd El-Aziz, Amos Lal, ElRashdy Redwan, Parise Adadi, Gaurav Chauhan, Samendra Sherchan, Gajendra Azad, Nima Rezaei, Ángel Serrano-Aroca, Nicolas Bazan, Sk Hassan, Pritam Panda, Pabitra Pal Choudhury, Damiano Pizzol, Ramesh Kandimalla, Wagner Baetas-Da-Cruz, Yogendra Mishra, Giorgio Palu, Adam Brufsky, Murtaza Tambuwala, Vladimir Uversky. COVID-19 Vaccines and Thrombosis—Roadblock or Dead-End Street? Biomolecules. 2021; 11 (7):1020.
Chicago/Turabian StyleKenneth Lundstrom; Debmalya Barh; Bruce Uhal; Kazuo Takayama; Alaa Aljabali; Tarek Abd El-Aziz; Amos Lal; ElRashdy Redwan; Parise Adadi; Gaurav Chauhan; Samendra Sherchan; Gajendra Azad; Nima Rezaei; Ángel Serrano-Aroca; Nicolas Bazan; Sk Hassan; Pritam Panda; Pabitra Pal Choudhury; Damiano Pizzol; Ramesh Kandimalla; Wagner Baetas-Da-Cruz; Yogendra Mishra; Giorgio Palu; Adam Brufsky; Murtaza Tambuwala; Vladimir Uversky. 2021. "COVID-19 Vaccines and Thrombosis—Roadblock or Dead-End Street?" Biomolecules 11, no. 7: 1020.
Glioblastoma is the most malignant and most common form of brain tumor, still today associated with a poor 14-months median survival from diagnosis. Protein kinase A, particularly its regulatory subunit R2Alpha, presents a typical intracellular distribution in glioblastoma cells compared to the healthy brain parenchyma and this peculiarity might be exploited in a therapeutic setting. In the present study, a third-generation lentiviral system for delivery of shRNA targeting the regulatory subunit R2Alpha of protein kinase A was developed. Generated lentiviral vectors are able to induce an efficient and stable downregulation of R2Alpha in different cellular models, including non-stem and stem-like glioblastoma cells. In addition, our data suggest a potential correlation between silencing of the regulatory subunit of protein kinase A and reduced viability of tumor cells, apparently due to a reduction in replication rate. Thus, our findings support the role of protein kinase A as a promising target for novel anti-glioma therapies.
Maira Zorzan; Claudia Del Vecchio; Stefania Vogiatzis; Elisa Saccon; Cristina Parolin; Giorgio Palù; Arianna Calistri; Carla Mucignat-Caretta. Targeting the Regulatory Subunit R2Alpha of Protein Kinase A in Human Glioblastoma through shRNA-Expressing Lentiviral Vectors. Viruses 2021, 13, 1361 .
AMA StyleMaira Zorzan, Claudia Del Vecchio, Stefania Vogiatzis, Elisa Saccon, Cristina Parolin, Giorgio Palù, Arianna Calistri, Carla Mucignat-Caretta. Targeting the Regulatory Subunit R2Alpha of Protein Kinase A in Human Glioblastoma through shRNA-Expressing Lentiviral Vectors. Viruses. 2021; 13 (7):1361.
Chicago/Turabian StyleMaira Zorzan; Claudia Del Vecchio; Stefania Vogiatzis; Elisa Saccon; Cristina Parolin; Giorgio Palù; Arianna Calistri; Carla Mucignat-Caretta. 2021. "Targeting the Regulatory Subunit R2Alpha of Protein Kinase A in Human Glioblastoma through shRNA-Expressing Lentiviral Vectors." Viruses 13, no. 7: 1361.
The estimated smooth curve of the percentage of subjects positive to SARS-CoV-2 started decreasing in Italy at the beginning of January 2021, due to the government containment measures undertaken from Christmas until 7 January. Approximately two weeks after releasing the measures, the curve stopped to decrease and remained approximately constant for four weeks to increase again in the middle of February. This epidemic phase had a public health care impact since, from the beginning of the fourth week of February, the curve of the intensive care unit’s occupancy started to grow. This wave of infection was characterized by the presence of new virus variants, with a higher than 80% dominance of the so-called “English” variant, since 15 April. School activities in Italy started at different times from 7 January until 8 February, depending on every region’s decision. Our present data on the incidence of SARS-CoV-2 in different age groups in Italy are in agreement with literature reports showing that subjects older than 10 years are involved in virus transmission. More importantly, we provide evidence to support the hypothesis that also individuals of age 0–9 years can significantly contribute to the spread of SARS-CoV-2.
Giovanni Sebastiani; Giorgio Palù. COVID-19 Pandemic: Influence of Schools, Age Groups, and Virus Variants in Italy. Viruses 2021, 13, 1269 .
AMA StyleGiovanni Sebastiani, Giorgio Palù. COVID-19 Pandemic: Influence of Schools, Age Groups, and Virus Variants in Italy. Viruses. 2021; 13 (7):1269.
Chicago/Turabian StyleGiovanni Sebastiani; Giorgio Palù. 2021. "COVID-19 Pandemic: Influence of Schools, Age Groups, and Virus Variants in Italy." Viruses 13, no. 7: 1269.
Human cytomegalovirus (HCMV) is a leading cause of severe diseases in immunocompromised individuals, including AIDS patients and transplant recipients, and in congenitally infected newborns. The utility of available drugs is limited by poor bioavailability, toxicity, and emergence of resistant strains. Therefore, it is crucial to identify new targets for therapeutic intervention. Among the latter, viral protein–protein interactions are becoming increasingly attractive. Since dimerization of HCMV DNA polymerase processivity factor ppUL44 plays an essential role in the viral life cycle, being required for oriLyt-dependent DNA replication, it can be considered a potential therapeutic target. We therefore performed an in silico screening and selected 18 small molecules (SMs) potentially interfering with ppUL44 homodimerization. Antiviral assays using recombinant HCMV TB4-UL83-YFP in the presence of the selected SMs led to the identification of four active compounds. The most active one, B3, also efficiently inhibited HCMV AD169 strain in plaque reduction assays and impaired replication of an AD169-GFP reporter virus and its ganciclovir-resistant counterpart to a similar extent. As assessed by Western blotting experiments, B3 specifically reduced viral gene expression starting from 48 h post infection, consistent with the inhibition of viral DNA synthesis measured by qPCR starting from 72 h post infection. Therefore, our data suggest that inhibition of ppUL44 dimerization could represent a new class of HCMV inhibitors, complementary to those targeting the DNA polymerase catalytic subunit or the viral terminase complex.
Hanieh Ghassabian; Federico Falchi; Martina Timmoneri; Beatrice Mercorelli; Arianna Loregian; Giorgio Palù; Gualtiero Alvisi. Divide et impera: An In Silico Screening Targeting HCMV ppUL44 Processivity Factor Homodimerization Identifies Small Molecules Inhibiting Viral Replication. Viruses 2021, 13, 941 .
AMA StyleHanieh Ghassabian, Federico Falchi, Martina Timmoneri, Beatrice Mercorelli, Arianna Loregian, Giorgio Palù, Gualtiero Alvisi. Divide et impera: An In Silico Screening Targeting HCMV ppUL44 Processivity Factor Homodimerization Identifies Small Molecules Inhibiting Viral Replication. Viruses. 2021; 13 (5):941.
Chicago/Turabian StyleHanieh Ghassabian; Federico Falchi; Martina Timmoneri; Beatrice Mercorelli; Arianna Loregian; Giorgio Palù; Gualtiero Alvisi. 2021. "Divide et impera: An In Silico Screening Targeting HCMV ppUL44 Processivity Factor Homodimerization Identifies Small Molecules Inhibiting Viral Replication." Viruses 13, no. 5: 941.
Aloe-emodin (1,8-dihydroxy-3-(hydroxymethyl)-anthraquinone), AE, is one of the active constituents of a number of plant species used in traditional medicine. We have previously identified, for the first time, AE as a new antitumor agent and shown that its selective in vitro and in vivo killing of neuroblastoma cells was promoted by a cell-specific drug uptake process. However, the molecular mechanism underlying the cell entry of AE has remained elusive as yet. In this report, we show that AE enters tumor cells via two of the five somatostatin receptors: SSTR2 and SSTR5. This observation was suggested by gene silencing, receptor competition, imaging and molecular modeling experiments. Furthermore, SSTR2 was expressed in all surgical neuroblastoma specimens we analyzed by immunohistochemistry. The above findings have strong implications for the clinical adoption of this natural anthraquinone molecule as an antitumor agent.
Teresa Pecere; Eleonora Ponterio; Enzo Di Iorio; Modesto Carli; Matteo Fassan; Luisa Santoro; Maicol Bissaro; Giulia Bernabè; Stefano Moro; Ignazio Castagliuolo; Giorgio Palù. On the mechanism of tumor cell entry of aloe‐emodin, a natural compound endowed with anticancer activity. International Journal of Cancer 2021, 149, 1129 -1136.
AMA StyleTeresa Pecere, Eleonora Ponterio, Enzo Di Iorio, Modesto Carli, Matteo Fassan, Luisa Santoro, Maicol Bissaro, Giulia Bernabè, Stefano Moro, Ignazio Castagliuolo, Giorgio Palù. On the mechanism of tumor cell entry of aloe‐emodin, a natural compound endowed with anticancer activity. International Journal of Cancer. 2021; 149 (5):1129-1136.
Chicago/Turabian StyleTeresa Pecere; Eleonora Ponterio; Enzo Di Iorio; Modesto Carli; Matteo Fassan; Luisa Santoro; Maicol Bissaro; Giulia Bernabè; Stefano Moro; Ignazio Castagliuolo; Giorgio Palù. 2021. "On the mechanism of tumor cell entry of aloe‐emodin, a natural compound endowed with anticancer activity." International Journal of Cancer 149, no. 5: 1129-1136.
Understanding the SARS-CoV-2 dynamics has been subject of intense research in the last months. In particular, accurate modeling of lockdown effects on human behaviour and epidemic evolution is a key issue in order e.g. to inform health-care decisions on emergency management. In this regard, the compartmental and spatial models so far proposed use parametric descriptions of the contact rate, often assuming a time-invariant effect of the lockdown. In this paper we show that these assumptions may lead to erroneous evaluations on the ongoing pandemic. Thus, we develop a new class of nonparametric compartmental models able to describe how the impact of the lockdown varies in time. Our estimation strategy does not require significant Bayes prior information and exploits regularization theory. Hospitalized data are mapped into an infinite-dimensional space, hence obtaining a function which takes into account also how social distancing measures and people’s growing awareness of infection’s risk evolves as time progresses. This also permits to reconstruct a continuous-time profile of SARS-CoV-2 reproduction number with a resolution never reached before in the literature. When applied to data collected in Lombardy, the most affected Italian region, our model illustrates how people behaviour changed during the restrictions and its importance to contain the epidemic. Results also indicate that, at the end of the lockdown, around $$12\%$$ 12 % of people in Lombardy and $$5\%$$ 5 % in Italy was affected by SARS-CoV-2, with the fatality rate being 1.14%. Then, we discuss how the situation evolved after the end of the lockdown showing that the reproduction number dangerously increased in the summer, due to holiday relax, reaching values larger than one on August 1, 2020. Finally, we also document how Italy faced the second wave of infection in the last part of 2020. Since several countries still observe a growing epidemic and others could be subject to other waves, the proposed reproduction number tracking methodology can be of great help to health care authorities to prevent SARS-CoV-2 diffusion or to assess the impact of lockdown restrictions on human behaviour to contain the spread.
G. Pillonetto; M. Bisiacco; G. Palù; C. Cobelli. Tracking the time course of reproduction number and lockdown’s effect on human behaviour during SARS-CoV-2 epidemic: nonparametric estimation. Scientific Reports 2021, 11, 1 -16.
AMA StyleG. Pillonetto, M. Bisiacco, G. Palù, C. Cobelli. Tracking the time course of reproduction number and lockdown’s effect on human behaviour during SARS-CoV-2 epidemic: nonparametric estimation. Scientific Reports. 2021; 11 (1):1-16.
Chicago/Turabian StyleG. Pillonetto; M. Bisiacco; G. Palù; C. Cobelli. 2021. "Tracking the time course of reproduction number and lockdown’s effect on human behaviour during SARS-CoV-2 epidemic: nonparametric estimation." Scientific Reports 11, no. 1: 1-16.
Human cytomegalovirus (HCMV) genome replication is a complex and still not completely understood process mediated by the highly coordinated interaction of host and viral products. Among the latter, six different proteins form the viral replication complex: a single-stranded DNA binding protein, a trimeric primase/helicase complex and a two subunit DNA polymerase holoenzyme, which in turn contains a catalytic subunit, pUL54, and a dimeric processivity factor ppUL44. Being absolutely required for viral replication and representing potential therapeutic targets, both the ppUL44–pUL54 interaction and ppUL44 homodimerization have been largely characterized from structural, functional and biochemical points of view. We applied fluorescence and bioluminescence resonance energy transfer (FRET and BRET) assays to investigate such processes in living cells. Both interactions occur with similar affinities and can take place both in the nucleus and in the cytoplasm. Importantly, single amino acid substitutions in different ppUL44 domains selectively affect its dimerization or ability to interact with pUL54. Intriguingly, substitutions preventing DNA binding of ppUL44 influence the BRETmax of protein–protein interactions, implying that binding to dsDNA induces conformational changes both in the ppUL44 homodimer and in the DNA polymerase holoenzyme. We also compared transiently and stably ppUL44-expressing cells in BRET inhibition assays. Transient expression of the BRET donor allowed inhibition of both ppUL44 dimerization and formation of the DNA polymerase holoenzyme, upon overexpression of FLAG-tagged ppUL44 as a competitor. Our approach could be useful both to monitor the dynamics of assembly of the HCMV DNA polymerase holoenzyme and for antiviral drug discovery.
Veronica Di Antonio; Giorgio Palù; Gualtiero Alvisi. Live-Cell Analysis of Human Cytomegalovirus DNA Polymerase Holoenzyme Assembly by Resonance Energy Transfer Methods. Microorganisms 2021, 9, 928 .
AMA StyleVeronica Di Antonio, Giorgio Palù, Gualtiero Alvisi. Live-Cell Analysis of Human Cytomegalovirus DNA Polymerase Holoenzyme Assembly by Resonance Energy Transfer Methods. Microorganisms. 2021; 9 (5):928.
Chicago/Turabian StyleVeronica Di Antonio; Giorgio Palù; Gualtiero Alvisi. 2021. "Live-Cell Analysis of Human Cytomegalovirus DNA Polymerase Holoenzyme Assembly by Resonance Energy Transfer Methods." Microorganisms 9, no. 5: 928.
The current Coronavirus Disease 19 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) shows similar pathology to MERS and SARS-CoV, with a current estimated fatality rate of 1.4%. Open reading frame 10 (ORF10) is a unique SARS-CoV-2 accessory protein, which contains eleven cytotoxic T lymphocyte (CTL) epitopes each of nine amino acids in length. Twenty-two unique SARS-CoV-2 ORF10 variants have been identified based on missense mutations found in sequence databases. Some of these mutations are predicted to decrease the stability of ORF10 in silico physicochemical and structural comparative analyses were carried out on SARS-CoV-2 and Pangolin-CoV ORF10 proteins, which share 97.37% amino acid (aa) homology. Though there is a high degree of ORF10 protein similarity of SARS-CoV-2 and Pangolin-CoV, there are differences of these two ORF10 proteins related to their sub-structure (loop/coil region), solubility, antigenicity and shift from strand to coil at aa position 26 (tyrosine). SARS-CoV-2 ORF10, which is apparently expressed in vivo since reactive T cell clones are found in convalescent patients should be monitored for changes which could correlate with the pathogenesis of COVID-19.
Sk. Sarif Hassan; Diksha Attrish; Shinjini Ghosh; Pabitra Pal Choudhury; Vladimir N. Uversky; Alaa A.A. Aljabali; Kenneth Lundstrom; Bruce D. Uhal; Nima Rezaei; Murat Seyran; Damiano Pizzol; Parise Adadi; Antonio Soares; Tarek Mohamed Abd El-Aziz; Ramesh Kandimalla; Murtaza M. Tambuwala; Gajendra Kumar Azad; Samendra P. Sherchan; Wagner Baetas-Da-Cruz; Amos Lal; Giorgio Palù; Kazuo Takayama; Ángel Serrano-Aroca; Debmalya Barh; Adam M. Brufsky. Notable sequence homology of the ORF10 protein introspects the architecture of SARS-CoV-2. International Journal of Biological Macromolecules 2021, 181, 801 -809.
AMA StyleSk. Sarif Hassan, Diksha Attrish, Shinjini Ghosh, Pabitra Pal Choudhury, Vladimir N. Uversky, Alaa A.A. Aljabali, Kenneth Lundstrom, Bruce D. Uhal, Nima Rezaei, Murat Seyran, Damiano Pizzol, Parise Adadi, Antonio Soares, Tarek Mohamed Abd El-Aziz, Ramesh Kandimalla, Murtaza M. Tambuwala, Gajendra Kumar Azad, Samendra P. Sherchan, Wagner Baetas-Da-Cruz, Amos Lal, Giorgio Palù, Kazuo Takayama, Ángel Serrano-Aroca, Debmalya Barh, Adam M. Brufsky. Notable sequence homology of the ORF10 protein introspects the architecture of SARS-CoV-2. International Journal of Biological Macromolecules. 2021; 181 ():801-809.
Chicago/Turabian StyleSk. Sarif Hassan; Diksha Attrish; Shinjini Ghosh; Pabitra Pal Choudhury; Vladimir N. Uversky; Alaa A.A. Aljabali; Kenneth Lundstrom; Bruce D. Uhal; Nima Rezaei; Murat Seyran; Damiano Pizzol; Parise Adadi; Antonio Soares; Tarek Mohamed Abd El-Aziz; Ramesh Kandimalla; Murtaza M. Tambuwala; Gajendra Kumar Azad; Samendra P. Sherchan; Wagner Baetas-Da-Cruz; Amos Lal; Giorgio Palù; Kazuo Takayama; Ángel Serrano-Aroca; Debmalya Barh; Adam M. Brufsky. 2021. "Notable sequence homology of the ORF10 protein introspects the architecture of SARS-CoV-2." International Journal of Biological Macromolecules 181, no. : 801-809.
(1) Background: A better understanding of COVID-19 dynamics in terms of interactions among individuals would be of paramount importance to increase the effectiveness of containment measures. Despite this, the research lacks spatiotemporal statistical and mathematical analysis based on large datasets. We describe a novel methodology to extract useful spatiotemporal information from COVID-19 pandemic data. (2) Methods: We perform specific analyses based on mathematical and statistical tools, like mathematical morphology, hierarchical clustering, parametric data modeling and non-parametric statistics. These analyses are here applied to the large dataset consisting of about 19,000 COVID-19 patients in the Veneto region (Italy) during the entire Italian national lockdown. (3) Results: We estimate the COVID-19 cumulative incidence spatial distribution, significantly reducing image noise. We identify four clusters of connected provinces based on the temporal evolution of the incidence. Surprisingly, while one cluster consists of three neighboring provinces, another one contains two provinces more than 210 km apart by highway. The survival function of the local spatial incidence values is modeled here by a tapered Pareto model, also used in other applied fields like seismology and economy in connection to networks. Model’s parameters could be relevant to describe quantitatively the epidemic. (4) Conclusion: The proposed methodology can be applied to a general situation, potentially helping to adopt strategic decisions such as the restriction of mobility and gatherings.
Ilaria Spassiani; Giovanni Sebastiani; Giorgio Palù. Spatiotemporal Analysis of COVID-19 Incidence Data. Viruses 2021, 13, 463 .
AMA StyleIlaria Spassiani, Giovanni Sebastiani, Giorgio Palù. Spatiotemporal Analysis of COVID-19 Incidence Data. Viruses. 2021; 13 (3):463.
Chicago/Turabian StyleIlaria Spassiani; Giovanni Sebastiani; Giorgio Palù. 2021. "Spatiotemporal Analysis of COVID-19 Incidence Data." Viruses 13, no. 3: 463.
Phylogenetic analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is focused on a single isolate of bat coronaviruses (bat CoVs) which does not adequately represent genetically related coronaviruses (CoVs)
Murat Seyran; Sk. Hassan; Vladimir Uversky; Pabitra Pal Choudhury; Bruce Uhal; Kenneth Lundstrom; Diksha Attrish; Nima Rezaei; Alaa Aljabali; Shinjini Ghosh; Damiano Pizzol; Parise Adadi; Tarek El-Aziz; Ramesh Kandimalla; Murtaza Tambuwala; Amos Lal; Gajendra Azad; Samendra Sherchan; Wagner Baetas-Da-Cruz; Giorgio Palù; Adam Brufsky. Urgent Need for Field Surveys of Coronaviruses in Southeast Asia to Understand the SARS-CoV-2 Phylogeny and Risk Assessment for Future Outbreaks. Biomolecules 2021, 11, 398 .
AMA StyleMurat Seyran, Sk. Hassan, Vladimir Uversky, Pabitra Pal Choudhury, Bruce Uhal, Kenneth Lundstrom, Diksha Attrish, Nima Rezaei, Alaa Aljabali, Shinjini Ghosh, Damiano Pizzol, Parise Adadi, Tarek El-Aziz, Ramesh Kandimalla, Murtaza Tambuwala, Amos Lal, Gajendra Azad, Samendra Sherchan, Wagner Baetas-Da-Cruz, Giorgio Palù, Adam Brufsky. Urgent Need for Field Surveys of Coronaviruses in Southeast Asia to Understand the SARS-CoV-2 Phylogeny and Risk Assessment for Future Outbreaks. Biomolecules. 2021; 11 (3):398.
Chicago/Turabian StyleMurat Seyran; Sk. Hassan; Vladimir Uversky; Pabitra Pal Choudhury; Bruce Uhal; Kenneth Lundstrom; Diksha Attrish; Nima Rezaei; Alaa Aljabali; Shinjini Ghosh; Damiano Pizzol; Parise Adadi; Tarek El-Aziz; Ramesh Kandimalla; Murtaza Tambuwala; Amos Lal; Gajendra Azad; Samendra Sherchan; Wagner Baetas-Da-Cruz; Giorgio Palù; Adam Brufsky. 2021. "Urgent Need for Field Surveys of Coronaviruses in Southeast Asia to Understand the SARS-CoV-2 Phylogeny and Risk Assessment for Future Outbreaks." Biomolecules 11, no. 3: 398.
Intracellular organelles enwrapped in membranes along with a complex network of vesicles trafficking in, out and inside the cellular environment are one of the main features of eukaryotic cells. Given their central role in cell life, compartmentalization and mechanisms allowing their maintenance despite continuous crosstalk among different organelles have been deeply investigated over the past years. Here, we review the multiple functions exerted by the endosomal sorting complex required for transport (ESCRT) machinery in driving membrane remodeling and fission, as well as in repairing physiological and pathological membrane damages. In this way, ESCRT machinery enables different fundamental cellular processes, such as cell cytokinesis, biogenesis of organelles and vesicles, maintenance of nuclear–cytoplasmic compartmentalization, endolysosomal activity. Furthermore, we discuss some examples of how viruses, as obligate intracellular parasites, have evolved to hijack the ESCRT machinery or part of it to execute/optimize their replication cycle/infection. A special emphasis is given to the herpes simplex virus type 1 (HSV-1) interaction with the ESCRT proteins, considering the peculiarities of this interplay and the need for HSV-1 to cross both the nuclear-cytoplasmic and the cytoplasmic-extracellular environment compartmentalization to egress from infected cells.
Arianna Calistri; Alberto Reale; Giorgio Palù; Cristina Parolin. Why Cells and Viruses Cannot Survive without an ESCRT. Cells 2021, 10, 483 .
AMA StyleArianna Calistri, Alberto Reale, Giorgio Palù, Cristina Parolin. Why Cells and Viruses Cannot Survive without an ESCRT. Cells. 2021; 10 (3):483.
Chicago/Turabian StyleArianna Calistri; Alberto Reale; Giorgio Palù; Cristina Parolin. 2021. "Why Cells and Viruses Cannot Survive without an ESCRT." Cells 10, no. 3: 483.
SARS-CoV-2 is highly contagious, rapidly turned into a pandemic, and is causing a relevant number of critical to severe life-threatening COVID-19 patients. However, robust statistical studies of a large cohort of patients, potentially useful to implement a vaccination campaign, are rare. We analyzed public data of about 19,000 patients for the period 28 February to 15 May 2020 by several mathematical methods. Precisely, we describe the COVID-19 evolution of a number of variables that include age, gender, patient’s care location, and comorbidities. It prompts consideration of special preventive and therapeutic measures for subjects more prone to developing life-threatening conditions while affording quantitative parameters for predicting the effects of an outburst of the pandemic on public health structures and facilities adopted in response. We propose a mathematical way to use these results as a powerful tool to face the pandemic and implement a mass vaccination campaign. This is done by means of priority criteria based on the influence of the considered variables on the probability of both death and infection.
Ilaria Spassiani; Lorenzo Gubian; Giorgio Palù; Giovanni Sebastiani. Vaccination Criteria Based on Factors Influencing COVID-19 Diffusion and Mortality. Vaccines 2020, 8, 766 .
AMA StyleIlaria Spassiani, Lorenzo Gubian, Giorgio Palù, Giovanni Sebastiani. Vaccination Criteria Based on Factors Influencing COVID-19 Diffusion and Mortality. Vaccines. 2020; 8 (4):766.
Chicago/Turabian StyleIlaria Spassiani; Lorenzo Gubian; Giorgio Palù; Giovanni Sebastiani. 2020. "Vaccination Criteria Based on Factors Influencing COVID-19 Diffusion and Mortality." Vaccines 8, no. 4: 766.
Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that is engendering the severe coronavirus disease 2019 (COVID-19) pandemic. The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 binds to the three sub-domains viz. amino acids (aa) 22–42, aa 79–84, and aa 330–393 of ACE2 on human cells to initiate entry. It was reported earlier that the receptor utilization capacity of ACE2 proteins from different species, such as cats, chimpanzees, dogs, and cattle, are different. A comprehensive analysis of ACE2 receptors of nineteen species was carried out in this study, and the findings propose a possible SARS-CoV-2 transmission flow across these nineteen species.
Sk. Sarif Hassan; Shinjini Ghosh; Diksha Attrish; Pabitra Pal Choudhury; Alaa A. A. Aljabali; Bruce D. Uhal; Kenneth Lundstrom; Nima Rezaei; Vladimir N. Uversky; Murat Seyran; Damiano Pizzol; Parise Adadi; Antonio Soares; Tarek Mohamed Abd El-Aziz; Ramesh Kandimalla; Murtaza M. Tambuwala; Gajendra Kumar Azad; Samendra P. Sherchan; Wagner Baetas-Da-Cruz; Kazuo Takayama; Ángel Serrano-Aroca; Gaurav Chauhan; Giorgio Palu; Adam M. Brufsky. Possible Transmission Flow of SARS-CoV-2 Based on ACE2 Features. Molecules 2020, 25, 5906 .
AMA StyleSk. Sarif Hassan, Shinjini Ghosh, Diksha Attrish, Pabitra Pal Choudhury, Alaa A. A. Aljabali, Bruce D. Uhal, Kenneth Lundstrom, Nima Rezaei, Vladimir N. Uversky, Murat Seyran, Damiano Pizzol, Parise Adadi, Antonio Soares, Tarek Mohamed Abd El-Aziz, Ramesh Kandimalla, Murtaza M. Tambuwala, Gajendra Kumar Azad, Samendra P. Sherchan, Wagner Baetas-Da-Cruz, Kazuo Takayama, Ángel Serrano-Aroca, Gaurav Chauhan, Giorgio Palu, Adam M. Brufsky. Possible Transmission Flow of SARS-CoV-2 Based on ACE2 Features. Molecules. 2020; 25 (24):5906.
Chicago/Turabian StyleSk. Sarif Hassan; Shinjini Ghosh; Diksha Attrish; Pabitra Pal Choudhury; Alaa A. A. Aljabali; Bruce D. Uhal; Kenneth Lundstrom; Nima Rezaei; Vladimir N. Uversky; Murat Seyran; Damiano Pizzol; Parise Adadi; Antonio Soares; Tarek Mohamed Abd El-Aziz; Ramesh Kandimalla; Murtaza M. Tambuwala; Gajendra Kumar Azad; Samendra P. Sherchan; Wagner Baetas-Da-Cruz; Kazuo Takayama; Ángel Serrano-Aroca; Gaurav Chauhan; Giorgio Palu; Adam M. Brufsky. 2020. "Possible Transmission Flow of SARS-CoV-2 Based on ACE2 Features." Molecules 25, no. 24: 5906.
Human cytomegalovirus (HCMV) is a leading cause of severe diseases in immunocompromised individuals, including AIDS and transplanted patients, and in congenitally infected newborns. The utility of available drugs is limited by poor bioavailability, toxicity, and emergence of resistant strains. Therefore, it is crucial to identify new targets of therapeutic intervention. Among the latter, viral protein-protein interactions are becoming increasingly attractive. Since dimerization of HCMV DNA polymerase processivity factor ppUL44 plays an essential role in the viral life cycle being required for oriLyt-dependent DNA replication, we performed an in silico screening and selected 18 small molecules (SMs) potentially interfering with ppUL44 homodimerization. Antiviral assays using recombinant HCMV TB40-UL83-YFP in the presence of the selected SMs led to the identification of four active compounds. The most active one, B3, also efficiently inhibited AD169 in plaque reduction assays and impaired replication of an AD169-GFP reporter virus and its ganciclovir-resistant counterpart to a similar extent. As assessed by Western blotting experiments, treatment of infected cells with B3 specifically reduced viral gene expression starting from 48 h post infection, consistent with activity on viral DNA synthesis. Therefore, inhibition of ppUL44 dimerization could represent a new class of HCMV inhibitors, complementary to those targeting the DNA polymerase catalytic subunit or the viral terminase complex.
Hanieh Ghassabian; Federico Falchi; Martina Timmoneri; Beatrice Mercorelli; Arianna Loregian; Giorgio Palù; Gualtiero Alvisi. Divide et Impera: An In Silico Screening Targeting HCMV ppUL44 Processivity Factor Homodimerization Identifies Small Molecules Inhibiting Viral Replication. 2020, 1 .
AMA StyleHanieh Ghassabian, Federico Falchi, Martina Timmoneri, Beatrice Mercorelli, Arianna Loregian, Giorgio Palù, Gualtiero Alvisi. Divide et Impera: An In Silico Screening Targeting HCMV ppUL44 Processivity Factor Homodimerization Identifies Small Molecules Inhibiting Viral Replication. . 2020; ():1.
Chicago/Turabian StyleHanieh Ghassabian; Federico Falchi; Martina Timmoneri; Beatrice Mercorelli; Arianna Loregian; Giorgio Palù; Gualtiero Alvisi. 2020. "Divide et Impera: An In Silico Screening Targeting HCMV ppUL44 Processivity Factor Homodimerization Identifies Small Molecules Inhibiting Viral Replication." , no. : 1.
After a linear growth during September, the diffusion in Italy of SARS-CoV-2, responsible for COVID-19, has been growing exponentially since the end of that month with a doubling time approximately equal to one week
Giovanni Sebastiani; Giorgio Palù. COVID-19 and School Activities in Italy. Viruses 2020, 12, 1339 .
AMA StyleGiovanni Sebastiani, Giorgio Palù. COVID-19 and School Activities in Italy. Viruses. 2020; 12 (11):1339.
Chicago/Turabian StyleGiovanni Sebastiani; Giorgio Palù. 2020. "COVID-19 and School Activities in Italy." Viruses 12, no. 11: 1339.
Background The high contagiousness and rapid spreading of the coronavirus disease 2019 (COVID-19) has been causing a quite relevant number of critical to severe-life threatening cases, that required urgent hospital admission and treatment in intensive care units (ICU). The pandemic has been a tough test for all European national health systems and their capability to provide an adequate reaction. Methods The present work aims to reveal correlation between parameters such as COVID-19 incidence, ICU bed occupancy, ICU excess area and mortality in Italian regions. Public data for the period of March 1 – July 16, 2020 were analyzed by several mathematical and statistical methods. Results The analysis could define two separate groups of Italian regions. The examined variables considered within these groups were interlinked and dependent one on each other. The regions of the two groups shared the same kind of model (linear) explaining mortality as a function of cumulative incidence, but with higher value of the constant in one group, so characterized by a high intrinsic "strength" of the pandemic, certainly playing a major role in the generation of a large number of severe and life-threatening cases. These results are confirmed at European level. Other factors can be conditioning mortality and be linked to incidence, such as ICU saturation and excess. Conclusions The quantitative results of the present study could be a very helpful tool to set up preventive measures and optimize biomedical interventions before the pandemic, in its recurrent waves, could overcome the reaction capacity of any public health system.
A. Olivieri; G. Palù; G. Sebastiani. COVID-19 cumulative incidence, intensive care, and mortality in Italian regions compared to selected European countries. International Journal of Infectious Diseases 2020, 102, 363 -368.
AMA StyleA. Olivieri, G. Palù, G. Sebastiani. COVID-19 cumulative incidence, intensive care, and mortality in Italian regions compared to selected European countries. International Journal of Infectious Diseases. 2020; 102 ():363-368.
Chicago/Turabian StyleA. Olivieri; G. Palù; G. Sebastiani. 2020. "COVID-19 cumulative incidence, intensive care, and mortality in Italian regions compared to selected European countries." International Journal of Infectious Diseases 102, no. : 363-368.
Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that is engendering the severe coronavirus disease 2019 (COVID-19) pandemic. The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 binds to the three sub-domains viz. amino acids (aa) 22-42, aa 79-84, and aa 330-393 of ACE2 on human cells to initiate entry. It was reported earlier that the receptor utilization capacity of ACE2 proteins from different species, such as cats, chimpanzees, dogs, and cattle, are different. A comprehensive analysis of ACE2 receptors of nineteen species was carried out in this study, and the findings propose a possible SARS-CoV-2 transmission flow across these nineteen species.
Sk. Sarif Hassan; Shinjini Ghosh; Diksha Attrish; Pabitra Pal Choudhury; Vladimir N Uversky; Bruce Uhal; Kenneth Lundstrom; Nima Rezaei; Alaa A.A Aljabali; Murat Seyran; Damiano Pizzol; Parise Adadi; Antonio Soares; Tarek Mohamed Abd El-Aziz; Ramesh Kandimalla; Murtaza Tambuwala; Gajendra Kumar Azad; Samendra P. Sherchan; Wagner Baetas-Da-Cruz; Kazuo Takayama; Angel Serrano-Aroca; Gaurav Chauhan; Giorgio Palu; Adam Brufsky. Possible transmission flow of SARS-CoV-2 based on ACE2 features. 2020, 1 .
AMA StyleSk. Sarif Hassan, Shinjini Ghosh, Diksha Attrish, Pabitra Pal Choudhury, Vladimir N Uversky, Bruce Uhal, Kenneth Lundstrom, Nima Rezaei, Alaa A.A Aljabali, Murat Seyran, Damiano Pizzol, Parise Adadi, Antonio Soares, Tarek Mohamed Abd El-Aziz, Ramesh Kandimalla, Murtaza Tambuwala, Gajendra Kumar Azad, Samendra P. Sherchan, Wagner Baetas-Da-Cruz, Kazuo Takayama, Angel Serrano-Aroca, Gaurav Chauhan, Giorgio Palu, Adam Brufsky. Possible transmission flow of SARS-CoV-2 based on ACE2 features. . 2020; ():1.
Chicago/Turabian StyleSk. Sarif Hassan; Shinjini Ghosh; Diksha Attrish; Pabitra Pal Choudhury; Vladimir N Uversky; Bruce Uhal; Kenneth Lundstrom; Nima Rezaei; Alaa A.A Aljabali; Murat Seyran; Damiano Pizzol; Parise Adadi; Antonio Soares; Tarek Mohamed Abd El-Aziz; Ramesh Kandimalla; Murtaza Tambuwala; Gajendra Kumar Azad; Samendra P. Sherchan; Wagner Baetas-Da-Cruz; Kazuo Takayama; Angel Serrano-Aroca; Gaurav Chauhan; Giorgio Palu; Adam Brufsky. 2020. "Possible transmission flow of SARS-CoV-2 based on ACE2 features." , no. : 1.
Despite the introduction of directly acting antivirals (DAAs), for the treatment of hepatitis C virus (HCV) infection, their cost, patient compliance, and viral resistance are still important issues to be considered. Here, we describe the generation of a novel JFH1-based HCV subgenomic replicon double reporter cell line suitable for testing different antiviral drugs and therapeutic interventions. This cells line allowed a rapid and accurate quantification of cell growth/viability and HCV RNA replication, thus discriminating specific from unspecific antiviral effects caused by DAAs or cytotoxic compounds, respectively. By correlating cell number and virus replication, we could confirm the inhibitory effect on the latter of cell over confluency and characterize an array of lentiviral vectors expressing single, double, or triple cassettes containing different combinations of short hairpin (sh)RNAs, targeting both highly conserved viral genome sequences and cellular factors crucial for HCV replication. While all vectors were effective in reducing HCV replication, the ones targeting viral sequences displayed a stronger antiviral effect, without significant cytopathic effects. Such combinatorial platforms as well as the developed double reporter cell line might find application both in setting-up anti-HCV gene therapy approaches and in studies aimed at further dissecting the viral biology/pathogenesis of infection.
Hossein M. Elbadawy; Mohi I. Mohammed Abdul; Naif Aljuhani; Adriana Vitiello; Francesco Ciccarese; Mohamed A. Shaker; Heba M. Eltahir; Giorgio Palù; Veronica Di Antonio; Hanieh Ghassabian; Claudia Del Vecchio; Cristiano Salata; Elisa Franchin; Eleonora Ponterio; Saleh Bahashwan; Khaled Thabet; Mekky M. Abouzied; Ahmed M. Shehata; Cristina Parolin; Arianna Calistri; Gualtiero Alvisi. Generation of Combinatorial Lentiviral Vectors Expressing Multiple Anti-Hepatitis C Virus shRNAs and Their Validation on a Novel HCV Replicon Double Reporter Cell Line. Viruses 2020, 12, 1044 .
AMA StyleHossein M. Elbadawy, Mohi I. Mohammed Abdul, Naif Aljuhani, Adriana Vitiello, Francesco Ciccarese, Mohamed A. Shaker, Heba M. Eltahir, Giorgio Palù, Veronica Di Antonio, Hanieh Ghassabian, Claudia Del Vecchio, Cristiano Salata, Elisa Franchin, Eleonora Ponterio, Saleh Bahashwan, Khaled Thabet, Mekky M. Abouzied, Ahmed M. Shehata, Cristina Parolin, Arianna Calistri, Gualtiero Alvisi. Generation of Combinatorial Lentiviral Vectors Expressing Multiple Anti-Hepatitis C Virus shRNAs and Their Validation on a Novel HCV Replicon Double Reporter Cell Line. Viruses. 2020; 12 (9):1044.
Chicago/Turabian StyleHossein M. Elbadawy; Mohi I. Mohammed Abdul; Naif Aljuhani; Adriana Vitiello; Francesco Ciccarese; Mohamed A. Shaker; Heba M. Eltahir; Giorgio Palù; Veronica Di Antonio; Hanieh Ghassabian; Claudia Del Vecchio; Cristiano Salata; Elisa Franchin; Eleonora Ponterio; Saleh Bahashwan; Khaled Thabet; Mekky M. Abouzied; Ahmed M. Shehata; Cristina Parolin; Arianna Calistri; Gualtiero Alvisi. 2020. "Generation of Combinatorial Lentiviral Vectors Expressing Multiple Anti-Hepatitis C Virus shRNAs and Their Validation on a Novel HCV Replicon Double Reporter Cell Line." Viruses 12, no. 9: 1044.