Diagnostic performance of hepatitis C core antigen assay to identify active infections: A systematic review and meta-analysis.

Hepatitis C virus (HCV) core antigen (HCVcAg) assay is an alternative for diagnosing HCV infection in a single step. This meta-analysis aimed to evaluate the Abbott ARCHITECT HCV Ag assay's diagnostic performance (validity and utility) for diagnosing active hepatitis C. PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library were searched until 10 January 2023. The protocol was registered at the prospective international register of systematic reviews (PROSPERO: CRD42022337191). Abbott ARCHITECT HCV Ag assay was the test for evaluation, and nucleic acid amplification tests with a cut-off ≤50 IU/mL were the gold standard. Statistical analysis was performed using STATA with the MIDAS module and random-effects models. The bivariate analysis was conducted on 46 studies (18,116 samples). The pooled sensitivity was 0.96 (95% CI = 0.94-0.97), specificity 0.99 (95% CI = 0.99-1.00), positive likelihood ratio 141.81 (95% CI = 72.39-277.79), and negative likelihood ratio 0.04 (95% CI = 0.03-0.06). The area under the summary receiver operating characteristic curve was 1.00 (95% CI = 0.34-1.00). For active hepatitis C prevalence values of 0.1%-15%, the probability that a positive test was a true positive was 12%-96%, respectively, indicating that a confirmatory test should be necessary, particularly with a prevalence ≤5%. However, the probability that a negative test was a false negative was close to zero, indicating the absence of HCV infection. The validity (accuracy) of the Abbott ARCHITECT HCV Ag assay for screening active HCV infection in serum/plasma samples was excellent. Although the HCVcAg assay showed limited diagnostic utility in low prevalence settings (≤1%), it might help diagnose hepatitis C in high prevalence scenarios (≥5%).

Diagnostic Performance of the HCV Core Antigen Test To Identify Hepatitis C in HIV-Infected Patients: a Systematic Review and Meta-Analysis.

The standard algorithm for diagnosing hepatitis C virus (HCV) infection has two steps, an HCV antibody test for screening and a nucleic acid amplification test (NAAT) for confirmation. However, the HCV core antigen (HCVcAg) detection assay is an alternative for one-step diagnosis. We aimed to evaluate the diagnostic performance of the Abbott ARCHITECT HCV Ag assay to detect active hepatitis C in serum/plasma in people living with HIV/AIDS (PLWHA), through a systematic review and meta-analysis. PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library were searched until 20 September 2022 (PROSPERO, CRD42022348351). We included studies evaluating Abbott ARCHITECT HCV Ag assay (index assay) versus NAATs (reference test) in PLWHA coinfected with HCV who did not receive antiviral treatment for HCV. Meta-analysis was performed with the MIDAS module using Stata and random-effects models. The QUADAS-2 tool evaluated the risk of bias. The bivariate analysis was conducted on 11 studies with 2,407 samples. Pooled sensitivity was 0.95 (95% CI = 0.92 to 0.97), specificity 0.97 (95% CI = 0.93 to 0.99), positive likelihood ratio 37.76 (95% CI = 12.84 to 111.02), and negative likelihood ratio 0.06 (95% CI = 0.04 to 0.09). The area under the curve was 0.97 (95% CI = 0.20 to 1.00). For low prevalence (≤5%), the posttest probability that an individual with a positive test was a true positive ranged from 4% to 67%, whereas, at high prevalence (≥10%), the posttest probability was between 81% and 87%, indicating that a confirmatory test should be necessary, particularly with prevalence values of ≤1%. Regardless of prevalence, the probability that an individual with a negative test was a false negative was close to zero, indicating that the individual was not infected with HCV. In conclusion, the accuracy of the Abbott ARCHITECT HCV Ag assay was very good for HCV screening in serum/plasma samples from PLWHA. The clinical utility to confirm HCV infection was acceptable in high-prevalence settings (≥10%) but poor in low-prevalence settings (≤1%). Furthermore, it was excellent in excluding active HCV infection.

IRF5-TNOP3 polymorphisms are associated with elite control of HIV infection: A retrospective study.

IRF5-TNPO3 polymorphisms have previously been related to immune response, and TNPO3 plays a role in human immunodeficiency virus (HIV)-1 infection after nuclear import. Therefore, we analyzed the genetic association between IRF5-TNPO3 polymorphisms and the HIV elite control in long-term nonprogressors (LTNPs). We performed a retrospective cohort study on 183 LTNPs, who were antiretroviral therapy-naïve with CD4+ ≥ 500 cells/mm3 , viral load ≤10 000 copies/mL, and asymptomatic over 10 years after HIV seroconversion. The primary outcome variable was HIV elite control (undetectable viral load in at least 90% of the measurements for at least 1 year). Seven IRF5-TNPO3 polymorphisms were genotyped using Agena Bioscience's MassARRAY platform. We found a significant association between specific IRF5-TNPO3 genotypes and HIV elite control: rs2004640 TT (aOR = 2.05; p = 0.041), rs10954213 AA (aOR = 1.95; p = 0.035), rs2280714 TT (aOR = 2.02; p = 0.031), and rs10279821 CC (aOR = 2.12; p = 0.017). We also found a significant association between IRF5-TNPO3 haplotype TATC composed of the favorable significant polymorphisms (rs2004640, rs10954213, rs2280714, and rs10279821) and the HIV elite control (aOR = 1.59; p = 0.048). IRF5-TNPO3 rs2004640, rs10954213, rs2280714, and rs10279821 polymorphisms were related to HIV elite control in LTNPs. Our data provide new knowledge about the impact of IRF5-TNPO3 polymorphisms on HIV pathogenesis to understand the phenomenon of natural HIV control.

IL7RA rs10491434 polymorphism is related to spontaneous HIV infection control in naïve HIV-infected patients: A retrospective study.

Interleukin 7 receptor (IL7R) is vital in the adaptive immune response against human immunodeficiency viruses (HIV). We assessed IL7RA polymorphisms (SNPs) in antiretroviral therapy (ART)-naïve HIV patients for their association with spontaneous HIV infection control. We conducted a retrospective cohort study involving 667 ART-naïve patients categorized by HIV progression (ordinal variable): 150 rapid progressors, 334 moderate/typical progressors, 86 long-term nonprogressors elite controllers (LTNPs-EC), and 97 LTNPs-non-EC. We genotyped three IL7RA SNPs using Agena Bioscience's MassARRAY platform. The association between IL7RA SNPs and spontaneous HIV infection control was evaluated using ordinal logistic regression. Individuals carrying the rs10491434 G allele have a higher likelihood of spontaneous HIV infection control (adjusted odds ratio [aOR] = 1.33; p = 0.023). Moreover, the IL7RA GCT haplotype, consisting of three specific SNPs (rs6897932, rs987106, and rs10491434), demonstrated an association with the control of untreated HIV infection (aOR = 1.34; p = 0.050). Remarkably, the rs10491434 SNP and the IL7RA GCT haplotype exhibited similar aOR values, suggesting that rs10491434 may be primarily responsible for the observed effect of the haplotype. IL7RA rs10491434 G allele is associated with a higher likelihood of spontaneous HIV infection control, indicating its significant role in the pathogenesis of HIV, possibly influencing infection course and viral replication control.

IgG antibody levels against the SARS-CoV-2 spike protein in mother-child dyads after COVID-19 vaccination.

PURPOSE: We aimed to assess IgG antibodies against the SARS-CoV-2 spike protein (anti-SARS-CoV-2 S IgG) in vaccinated mothers and their infants at delivery and 2-3 months of age. METHODS: We conducted a prospective study on mothers who received at least one dose of the COVID-19 vaccine (Pfizer-BNT162b2, Moderna mRNA-1273, or Oxford-AstraZeneca ChAdOx1-S) during pregnancy and on their infants. The baseline was at the time of delivery (n = 93), and the end of follow-up was 2 to 3 months post-partum (n = 53). Serum anti-SARS-CoV-2 S IgG titers and ACE2 binding inhibition levels were quantified by immunoassays. RESULTS: Mothers and infants had high anti-SARS-CoV-2 S IgG titers against the B.1 lineage at birth. However, while antibody titers were maintained at 2-3 months post-partum in mothers, they decreased significantly in infants (p < 0.001). Positive and significant correlations were found between anti-SARS-CoV-2 S IgG titers and ACE2-binding inhibition levels in mothers and infants at birth and 2-3 months post-partum (r > 0.8, p < 0.001). Anti-S antibodies were also quantified for the Omicron variant at 2-3 months post-partum. The antibody titers against Omicron were significantly lower in mothers and infants than those against B.1 (p < 0.001). Again, a positive correlation was observed for Omicron between IgG titers and ACE2-binding inhibition both in mothers (r = 0.818, p < 0.001) and infants (r = 0.386, p < 0.005). Previous SARS-CoV-2 infection and COVID-19 vaccination near delivery positively impacted anti-SARS-CoV-2 S IgG levels. CONCLUSIONS: COVID-19 mRNA vaccines induce high anti-SARS-CoV-2 S titers in pregnant women, which can inhibit the binding of ACE2 to protein S and are efficiently transferred to the fetus. However, there was a rapid decrease in antibody levels at 2 to 3 months post-partum, particularly in infants.

Antibody levels to SARS-CoV-2 spike protein in mothers and children from delivery to six months later.

INTRODUCTION: Pregnant women are vulnerable to severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. Neutralizing antibodies against the SARS-CoV-2 spike (S) protein protect from severe disease. This study analyzes the antibody titers to SARS-CoV-2 S protein in pregnant women and their newborns at delivery, and six months later. METHODS: We conducted a prospective study on pregnant women with confirmed SARS-CoV-2 infection and newborns. Antibody (IgG, IgM, and IgA) titers were determined using immunoassays in serum and milk samples. An angiotensin-converting enzyme 2 (ACE2) receptor-binding inhibition assay to the S protein was performed on the same serum and milk samples. RESULTS: At birth, antibodies to SARS-CoV-2 spike protein were detected in 81.9% of mothers' sera, 78.9% of cord blood samples, and 63.2% of milk samples. Symptomatic women had higher antibody titers (IgG, IgM, and IgA) than the asymptomatic ones (P < 0.05). At six months postpartum, IgG levels decreased drastically in children's serum (P < 0.001) but remained high in mothers' serum. Antibody titers correlated positively with its capacity to inhibit the ACE2-spike protein interaction at baseline in maternal sera (R2  = 0.203; P < 0.001), cord sera (R2  = 0.378; P < 0.001), and milk (R2  = 0.564; P < 0.001), and at six months in maternal sera (R2  = 0.600; P < 0.001). CONCLUSIONS: High antibody levels against SARS-CoV-2 spike protein were found in most pregnant women. Due to the efficient transfer of IgG to cord blood and high IgA titers in breast milk, neonates may be passively immunized to SARS-CoV-2 infection. Our findings could guide newborn management and maternal vaccination policies.

Environmental factors linked to hospital admissions in young children due to acute viral lower respiratory infections: A bidirectional case-crossover study.

OBJECTIVE: This study evaluated the association of the short-term exposure to environmental factors (relative humidity, temperature, NO2, SO2, O3, PM10, and CO) with hospital admissions due to acute viral lower respiratory infections (ALRI) in children under two years before the COVID-19 era. METHODS: We performed a bidirectional case-crossover study in 30,445 children with ALRI under two years of age in the Spanish Minimum Basic Data Set (MBDS) from 2013 to 2015. Environmental data were obtained from Spain's State Meteorological Agency (AEMET). The association was assessed by conditional logistic regression. RESULTS: Lower temperature one week before the day of the event (hospital admission) (q-value = 0.012) and higher relative humidity one week (q-value = 0.003) and two weeks (q-value<0.001) before the day of the event were related to a higher odds of hospital admissions. Higher NO2 levels two weeks before the event were associated with hospital admissions (q-value<0.001). Moreover, higher concentrations on the day of the event for SO2 (compared to lag time of 1-week (q-value = 0.026) and 2-weeks (q-value<0.001)), O3 (compared to lag time of 3-days (q-value<0.001), 1-week (q-value<0.001), and 2-weeks (q-value<0.001)), and PM10 (compared to lag time of 2-weeks (q-value<0.001)) were related to an increased odds of hospital admissions for viral ALRI. CONCLUSION: Short-term exposure to environmental factors (climatic conditions and ambient air contaminants) was linked to a higher likelihood of hospital admissions due to ALRI. Our findings emphasize the importance of monitoring environmental factors to assess the odds of ALRI hospital admissions and plan public health resources.

Neighborhood environmental factors linked to hospitalizations of older people for viral lower respiratory tract infections in Spain: a case-crossover study.

BACKGROUND: Lower respiratory tract viral infection (LRTI) is a significant cause of morbidity-mortality in older people worldwide. We analyzed the association between short-term exposure to environmental factors (climatic factors and outdoor air pollution) and hospital admissions with a viral LRTI diagnosis in older adults. METHODS: We conducted a bidirectional case-crossover study in 6367 patients over 65 years of age with viral LRTI and residential zip code in the Spanish Minimum Basic Data Set. Spain's State Meteorological Agency was the source of environmental data. Associations were assessed using conditional logistic regression. P-values were corrected for false discovery rate (q-values). RESULTS: Almost all were hospital emergency admissions (98.13%), 18.64% were admitted to the intensive care unit (ICU), and 7.44% died. The most frequent clinical discharge diagnosis was influenza (90.25%). LRTI hospital admissions were more frequent when there were lower values of temperature and O3 and higher values of relative humidity and NO2. The regression analysis adjusted by temperatures and relative humidity showed higher concentrations at the hospital admission for NO2 [compared to the lag time of 1-week (q-value< 0.001) and 2-weeks (q-value< 0.001)] and O3 [compared to the lag time of 3-days (q-value< 0.001), 1-week (q-value< 0.001), and 2-weeks (q-value< 0.001)] were related to a higher odds of hospital admissions due to viral LRTI. Moreover, higher concentrations of PM10 at the lag time of 1-week (q-value = 0.023) and 2-weeks (q-value = 0.002), and CO at the lag time of 3-days (q-value = 0.023), 1-week (q-value< 0.001) and 2-weeks (q-value< 0.001)], compared to the day of hospitalization, were related to a higher chances of hospital admissions with viral LRTI. CONCLUSION: Unfavorable environmental factors (low temperatures, high relative humidity, and high concentrations of NO2, O3, PM10, and CO) increased the odds of hospital admissions with viral LRTI among older people, indicating they are potentially vulnerable to these environmental factors.

Interacting Quantum Atoms Method for Crystalline Solids.

An implementation of the Interacting Quantum Atoms method for crystals is presented. It provides a real space energy decomposition of the energy of crystals in which all energy components are physically meaningful. The new package ChemInt enables one to compute intra-atomic and inter-atomic energies, as well as electron population measures used for quantitative description of chemical bonds in crystals. The implementation is tested and applied to characteristic molecular and crystalline systems with different types of bonding.

Drug discovery technologies: Caenorhabditis elegans as a model for anthelmintic therapeutics.

Helminthiasis is one of the gravest problems worldwide. There is a growing concern on less available anthelmintics and the emergence of resistance creating a major threat to human and livestock health resources. Novel and broad-spectrum anthelmintics are urgently needed. The free-living nematode Caenorhabditis elegans could address this issue through automated high-throughput technologies for the screening of large chemical libraries. This review discusses the strong advantages and limitations for using C elegans as a screening method for anthelmintic drug discovery. C elegans is the best model available for the validation of novel effective drugs in treating most, if not all, helminth infections, and for the elucidation the mode of action of anthelmintic candidates. This review also focuses on available technologies in the discovery of anthelmintics published over the last 15 years with particular attention to high-throughput technologies over conventional screens. On the other hand, this review highlights how combinatorial and nanomedicine strategies could prolong the use of anthelmintics and control resistance problems.

Hepatitis C virus vaccine design: focus on the humoral immune response.

Despite the recent development of safe and highly effective direct-acting antivirals, hepatitis C virus (HCV) infection remains a significant health problem. In 2016, the World Health Organization set out to reduce the rate of new HCV infections by 90% by 2030. Still, global control of the virus does not seem to be achievable in the absence of an effective vaccine. Current approaches to the development of a vaccine against HCV include the production of recombinant proteins, synthetic peptides, DNA vaccines, virus-like particles, and viral vectors expressing various antigens. In this review, we focus on the development of vaccines targeting the humoral immune response against HCV based on the cumulative evidence supporting the important role of neutralizing antibodies in protection against HCV infection. The main targets of HCV-specific neutralizing antibodies are the glycoproteins E1 and E2. Recent advances in the knowledge of HCV glycoprotein structure and their epitopes, as well as the possibility of getting detailed information on the human antibody repertoire generated by the infection, will allow rational structure-based antigen design to target specific germline antibodies. Although obtaining a vaccine capable of inducing sterilizing immunity will be a difficult task, a vaccine that prevents chronic hepatitis C infections, a more realistic goal in the short term, would have a considerable health impact.

Screening Marine Natural Products for New Drug Leads against Trypanosomatids and Malaria.

Neglected Tropical Diseases (NTD) represent a serious threat to humans, especially for those living in poor or developing countries. Almost one-sixth of the world population is at risk of suffering from these diseases and many thousands die because of NTDs, to which we should add the sanitary, labor and social issues that hinder the economic development of these countries. Protozoan-borne diseases are responsible for more than one million deaths every year. Visceral leishmaniasis, Chagas disease or sleeping sickness are among the most lethal NTDs. Despite not being considered an NTD by the World Health Organization (WHO), malaria must be added to this sinister group. Malaria, caused by the apicomplexan parasite Plasmodium falciparum, is responsible for thousands of deaths each year. The treatment of this disease has been losing effectiveness year after year. Many of the medicines currently in use are obsolete due to their gradual loss of efficacy, their intrinsic toxicity and the emergence of drug resistance or a lack of adherence to treatment. Therefore, there is an urgent and global need for new drugs. Despite this, the scant interest shown by most of the stakeholders involved in the pharmaceutical industry makes our present therapeutic arsenal scarce, and until recently, the search for new drugs has not been seriously addressed. The sources of new drugs for these and other pathologies include natural products, synthetic molecules or repurposing drugs. The most frequent sources of natural products are microorganisms, e.g., bacteria, fungi, yeasts, algae and plants, which are able to synthesize many drugs that are currently in use (e.g. antimicrobials, antitumor, immunosuppressants, etc.). The marine environment is another well-established source of bioactive natural products, with recent applications against parasites, bacteria and other pathogens which affect humans and animals. Drug discovery techniques have rapidly advanced since the beginning of the millennium. The combination of novel techniques that include the genetic modification of pathogens, bioimaging and robotics has given rise to the standardization of High-Performance Screening platforms in the discovery of drugs. These advancements have accelerated the discovery of new chemical entities with antiparasitic effects. This review presents critical updates regarding the use of High-Throughput Screening (HTS) in the discovery of drugs for NTDs transmitted by protozoa, including malaria, and its application in the discovery of new drugs of marine origin.

G2-S16 dendrimer microbicide does not interfere with the vaginal immune system.

It is essential that prophylactic drugs do not interfere with the normal function of the immune system. The use of nanoparticles as vaginal microbicides is a promising prevention strategy against sexually transmitted infections. With that aim, our group is working with the G2-S16, a second generation carbosilane dendrimer with sulfonate groups in the periphery, which has been previously shown to be effective against HIV-1 and HSV-2 infection, and it is now on the road to clinical trials. Our objective in this new study is to assess the effects of G2-S16 on the immune barrier of the female reproductive tract. The expression of differentiation, maturation and activation markers was measured in epithelial cells, dendritic cells, M and GM macrophages, and T cells using RT-qPCR and flow cytometry. The results demonstrate that G2-S16 does not alter the natural immunity of the vagina, strongly supporting the biosafety of this dendrimer for clinical use.

Real-Space In Situ Bond Energies: Toward A Consistent Energetic Definition of Bond Strength.

A rigorous definition of intrinsic bond strength based on the partitioning of a molecule into real-space fragments is presented. Using the domains provided by the quantum theory of atoms-in-molecules (QTAIM) together with the interacting quantum atoms (IQA) energetic decomposition, we show how an in situ bond strength, matching all the requirements of an intrinsic bond energy, can be defined between each pair of fragments. Total atomization or fragmentation energies are shown to be equal to the sum of these in situ bond energies (ISBEs) if the energies of the fragments are measured with respect to their in-the-molecule state. These energies usually lie above the ground state of the isolated fragments by quantities identified with the standard fragment relaxation or deformation energies, which are also provided by the protocol. Deformation energies bridge dissociation energies with ISBEs, and can be dissected by using well-known tools of real-space theories of chemical bonding. Similarly, ISBEs can be partitioned into ionic and covalent contributions, and this feature adds to the chemical appeal of the procedure. All the energetic quantities examined are observable and amenable, in principle, to experimental determination. Several systems, exemplifying the role of each energetic term presented herein, are used to show the power of the approach.

Actionable pathways: interactive discovery of therapeutic targets using signaling pathway models.

The discovery of actionable targets is crucial for targeted therapies and is also a constituent part of the drug discovery process. The success of an intervention over a target depends critically on its contribution, within the complex network of gene interactions, to the cellular processes responsible for disease progression or therapeutic response. Here we present PathAct, a web server that predicts the effect that interventions over genes (inhibitions or activations that simulate knock-outs, drug treatments or over-expressions) can have over signal transmission within signaling pathways and, ultimately, over the cell functionalities triggered by them. PathAct implements an advanced graphical interface that provides a unique interactive working environment in which the suitability of potentially actionable genes, that could eventually become drug targets for personalized or individualized therapies, can be easily tested. The PathAct tool can be found at: http://pathact.babelomics.org.

Mechanistic Studies of Viral Entry: An Overview of Dendrimer-Based Microbicides As Entry Inhibitors Against Both HIV and HSV-2 Overlapped Infections.

This review provides an overview of the development of different dendrimers, mainly polyanionic, against human immunodeficiency virus (HIV) and genital herpes (HSV-2) as topical microbicides targeting the viral entry process. Vaginal topical microbicides to prevent sexually transmitted infections such as HIV and HSV-2 are urgently needed. To inhibit HIV/HSV-2 entry processes, new preventive targets have been established to maximize the current therapies against wild-type and drug-resistant viruses. The entry of HIV/HSV-2 into target cells is a multistep process that triggers a cascade of molecular interactions between viral envelope proteins and cell surface receptors. Polyanionic dendrimers are highly branched nanocompounds with potent activity against HIV/HSV-2. Inhibitors of each entry step have been identified with regard to generations and surface groups, and possible roles for these agents in anti-HIV/HSV-2 therapies have also been discussed. Four potential binding sites for impeding HIV infection (HSPG, DC-SIGN, GSL, and CD4/gp120 inhibitors) and HSV-2 infection (HS, gB, gD, and gH/gL inhibitors) exist according to their mechanisms of action and structures. This review clarifies that inhibition of HIV/HSV-2 entry continues to be a promising target for drug development because nanotechnology can transform the field of HIV/HSV-2 prevention by improving the efficacy of the currently available antiviral treatments.

A multipolar approach to the interatomic covalent interaction energy.

Interatomic exchange-correlation energies correspond to the covalent energetic contributions to an interatomic interaction in real space theories of the chemical bond, but their widespread use is severely limited due to their computationally intensive character. In the same way as the multipolar (mp) expansion is customary used in biomolecular modeling to approximate the classical Coulomb interaction between two charge densities ρA(r) and ρB(r), we examine in this work the mp approach to approximate the interatomic exchange-correlation (xc) energies of the Interacting Quantum Atoms method. We show that the full xc mp series is quickly divergent for directly bonded atoms (1-2 pairs) albeit it works reasonably well most times for 1- n (n > 2) interactions. As with conventional perturbation theory, we show numerically that the xc series is asymptotically convergent and that, a truncated xc mp approximation retaining terms up to l1+l2=2 usually gives relatively accurate results, sometimes even for directly bonded atoms. Our findings are supported by extensive numerical analyses on a variety of systems that range from several standard hydrogen bonded dimers to typically covalent or aromatic molecules. The exact algebraic relationship between the monopole-monopole xc mp term and the inter-atomic bond order, as measured by the delocalization index of the quantum theory of atoms in molecules, is also established. © 2017 Wiley Periodicals, Inc.

An unexpected bridge between chemical bonding indicators and electrical conductivity through the localization tensor.

While the modern theory of the insulating state shows that the conducting or insulating properties of a system can be extracted solely from the ground state properties via the so-called localization tensor (LT), no chemical reading of this important quantity has ever been offered. Here, a remarkable link between the LT and the bond orders as described by the delocalization indices (DIs) of chemical bonding theory is reported. This is achieved through a real space partition of the LT into intra- and interatomic contributions. We show that the convergence or divergence of the LT in the thermodynamic limit, which signals the insulating or conducting nature of an extended system, respectively, can be nailed down to DIs. This allows for the exploitation of traditional chemical intuition to identify essential and spectator atomic groups in determining electrical conductivity. The thermodynamic limit of the LT is controlled by the spatial decay rate of the interatomic DIs, exponential in insulators and power-law in conductors. Computational data of a few selected toy systems corroborate our results.

Polyanionic carbosilane dendrimers prevent hepatitis C virus infection in cell culture.

Hepatitis C virus (HCV) infection is a major biomedical problem worldwide. Although new direct antiviral agents (DAAs) have been developed for the treatment of chronic HCV infection, the potential emergence of resistant virus variants and the difficulties to implement their administration worldwide make the development of novel antiviral agents an urgent need. Moreover, no effective vaccine is available against HCV and transmission of the virus still occurs particularly when prophylactic measures are not taken. We used a cell-based system to screen a battery of polyanionic carbosilane dendrimers (PCDs) to identify compounds with antiviral activity against HCV and show that they inhibit effective virus adsorption of major HCV genotypes. Interestingly, one of the PCDs irreversibly destabilized infectious virions. This compound displays additive effect in combination with a clinically relevant DAA, sofosbuvir. Our results support further characterization of these molecules as nanotools for the control of hepatitis C virus spread.

Effect of Several HIV Antigens Simultaneously Loaded with G2-NN16 Carbosilane Dendrimer in the Cell Uptake and Functionality of Human Dendritic Cells.

Dendrimers are highly branched, star-shaped, and nanosized polymers that have been proposed as new carriers for specific HIV-1 peptides. Dendritic cells (DCs) are the most-potent antigen-presenting cells that play a major role in the development of cell-mediated immunotherapy due to the generation and regulation of adaptive immune responses against HIV-1. This article reports on the associated behavior of two or three HIV-derived peptides simultaneously (p24/gp160 or p24/gp160/NEF) with cationic carbosilane dendrimer G2-NN16. We have found that (i) immature DCs (iDCs) and mature (mDCs) did not capture efficiently HIV peptides regarding the uptake level when cells were treated with G2-NN16-peptide complex alone; (ii) the ability of DCs to migrate was not depending on the peptides presence; and (iii) with the use of molecular dynamic simulation, a mixture of peptides decreased the cell uptake of the other peptides (in particular, NEF hinders the binding of more peptides and is especially obstructing of the binding of gp160 to G2-NN16). The results suggest that G2-NN16 cannot be considered as an alternative carrier for delivering two or more HIV-derived peptides to DCs.