When Tautomers Matter: UV-Vis Absorption Spectra of Hypoxanthine in Aqueous Solution from Fully Atomistic Simulations.

The UV-Vis spectrum of the solvated purine derivative Hypoxanthine (HYX) is investigated using the Quantum Mechanics/Fluctuating Charges (QM/FQ) multiscale approach combined with a sampling of configurations through atomistic Molecular Dynamics (MD) simulations. Keto 1H7H and 1H9H tautomeric forms of HYX are the most stable in aqueous solution and form different stable complexes with the surrounding water molecules, ultimately affecting the electronic absorption spectra. The final simulated spectrum resulting from the combination of the individual spectra of tautomers agrees very well with most of the characteristics in the measured spectrum. The importance of considering the effect of the solute tautomers and, in parallel, the contribution of the different solvent arrangements around the solute when modeling spectral properties, is highlighted. In addition, the high quality of the computed spectra leads to suggesting an alternative way for acquiring tautomeric populations from combined computational/experimental spectra.

Encapsulation of charged halogens by the 512 water cage.

This study focuses on the encapsulation of the entire series of halides by the 512 cage of twenty water molecules and on the characterization of water to water and water to anion interactions. State-of-the-art computations are used to determine equilibrium geometries, energy related quantities, and thermal stability towards dissociation and to dissect the nature and strength of intermolecular interactions holding the clusters as stable units. Two types of structures are revealed: heavily deformed cages for F- indicating a preference for microsolvation, and slightly deformed cages for the remaining anions indicating a preference for encapsulation. The primary variable dictating the properties of the clusters is the charge density of the central halide, with the most severe effects observed for the F- case. For the remaining halides, the anion may be safely viewed as a sort of "big electron" with little local disruptive power, enough to affect the network of non-covalent hydrogen bonds in the cage, but not enough to break it. Gibbs energies for dissociation either into cavity and halide or into water molecules and halide suggest that, in a similar way as to methane clathrate, a more weakly bonded complex that has been detected in the gas phase, all halide containing clathrate-like structures should be amenable to experimental detection in the gas phase at moderate temperature and pressure conditions.

Interactions and reactivity in crystalline intermediates of mechanochemical cyclorhodation reactions.

There is experimental evidence that solid mixtures of the rhodium dimer [Cp*RhCl2]2 and benzo[h] quinoline (BHQ) produce two different polymorphic molecular cocrystals called 4α and 4ß under ball milling conditions. The addition of NaOAc to the mixture leads to the formation of the rhodacycle [Cp*Rh-(BHQ)Cl], where the central Rh atom retains its tetracoordinate character. Isolate 4ß reacts with NaOAc leading to the same rhodacycle while isolate 4α does not under the same conditions. We show that the puzzling difference in reactivity between the two cocrystals can be traced back to fundamental aspects of the intermolecular interactions between the BHQ and [Cp*RhCl2]2 fragments in the crystalline environment. To support this view, we report a number of descriptors of the nature and strength of chemical bonds and intermolecular interactions in the extended solids and in a cluster model. We calculate formal quantum mechanical descriptors based on electronic structure, electron density, and binding and interaction energies including an energy decomposition analysis. Without exception, all descriptors point to 4ß being a transient structure higher in energy than 4α with larger local and global electrophilic and nucleophilic powers, a more favorable spatial and energetic distribution of the frontier orbitals, and a more fragile crystal structure.

Development of mental health first-aid guidelines for a person after a potentially traumatic event: A Delphi expert consensus study in Argentina and Chile.

BACKGROUND: Exposure to potentially traumatic events increases the risk of a person developing a mental disorder. Training community members to offer support to a person during and after a traumatic situation may help lower this risk. This study reports on the cultural adaptation of Australian mental health first aid guidelines for individuals exposed to a potentially traumatic event to the Chilean and Argentinian context. METHODS: A Delphi expert consensus study was conducted with two panels of experts, one of people with lived experience of trauma (either their own or as a carer; n = 26) and another one of health professionals (n = 41). A total of 158 items, drawn from guidelines developed by Australian experts in 2019, were translated to Spanish and evaluated in a two-round survey process. The panellists were asked to rate each item on a five-point Likert scale; statements were included in the final guidelines if 80% of both panels endorsed the item as "essential" or "important". RESULTS: Consensus was achieved on 142 statements over two survey rounds. A total of 102 statements were included from the English-language guidelines, and 40 locally generated statements were accepted in the second round. Local experts endorsed a larger number of items compared to their counterparts in Australia and emphasised the importance of acknowledging the first aider's limitations, both personally and as part of their helping role. Additional items about working as a team with other first responders and considering helping the person's significant others were endorsed by the local panellists. CONCLUSIONS: The study showed a high level of acceptance of the original actions suggested for inclusion in the guidelines for Australia, but also a significant number of new statements that highlight the importance of the adaptation process. Further research on the dissemination of these guidelines into a Mental Health First Aid training course for Chile and Argentina is still required.

Development of mental health first-aid guidelines for psychosis: a Delphi expert consensus study in Argentina and Chile.

BACKGROUND: Psychotic symptoms may be less common than anxiety or affective symptoms, but they are still frequent and typically highly debilitating. Community members can have a role in helping to identify, offer initial help and facilitate access to mental health services of individuals experiencing psychosis. Mental health first aid guidelines for helping a person experiencing psychosis have been developed for the global north. This study aimed to adapt the English- language guidelines for Chile and Argentina. METHODS: A Delphi expert consensus study was conducted with two panels of experts, one of people with lived experience of psychosis (either their own or as a carer; n = 29) and another one of health professionals (n = 29). Overall, 249 survey items from the original English guidelines and 26 items suggested by the local team formed a total of 275 that were evaluated in the first round. Participants were invited to rate how essential or important those statements were for Chile and Argentina, and encouraged to suggest new statements if necessary. These were presented in a second round. Items with 80% of endorsement by both panels were included in the guidelines for Chile and Argentina. RESULTS: Data were obtained over two survey rounds. Consensus was achieved on 244 statements, including 26 statements locally generated for the second round. Almost 20% of the English statements were not endorsed (n = 50), showing the applicability of the original guidelines but also the importance of culturally adapting them. Attributions and tasks expected to be delivered by first aiders were shrunk in favour of a greater involvement of mental health professionals. Self-help strategies were mostly not endorsed and as were items relating to respecting the person's autonomy. CONCLUSIONS: While panellists agreed that first aiders should be aware of human rights principles, items based on recovery principles were only partially endorsed. Further research on the dissemination of these guidelines and development of a Mental Health First Aid training course for Chile and Argentina is still required.

Protein-Protein Binding Kinetics by Biolayer Interferometry.

The specific kinetics and thermodynamics of protein-protein interactions underlie the molecular mechanisms of cellular functions; hence the characterization of these interaction parameters is central to the quantitative understanding of physiological and pathological processes. Many methods have been developed to study protein-protein interactions, which differ in various features including the interaction detection principle, the sensitivity, whether the method operates in vivo, in vitro, or in silico, the temperature control, the use of labels, immobilization, the amount of sample required, the number of measurements that can be accomplished simultaneously, or the cost. Bio-Layer Interferometry (BLI) is a label-free biophysical method to measure the kinetics of protein-protein interactions. Label-free interaction assays are a broad family of methods that do not require protein modifications (other than immobilization) or labels such as fusions with fluorescent proteins or transactivating domains or chemical modifications like biotinylation or reaction with radionuclides. Besides BLI, other label-free techniques that are widely used for determining protein-protein interactions include surface plasmon resonance (SPR), thermophoresis, and isothermal titration calorimetry (ITC), among others.

Transient Structural Properties of the Rho GDP-Dissociation Inhibitor.

Rho GTPases, master spatial regulators of a wide range of cellular processes, are orchestrated by complex formation with guanine nucleotide dissociation inhibitors (RhoGDIs). These have been thought to possess an unstructured N-terminus that inhibits nucleotide exchange of their client upon binding/folding. Via NMR analyses, molecular dynamics simulations, and biochemical assays, we reveal instead pertinent structural properties transiently maintained both, in the presence and absence of the client, imposed onto the terminus context-specifically by modulating interactions with the surface of the folded C-terminal domain. These observations revise the long-standing textbook picture of the GTPases' mechanism of membrane extraction. Rather than by a disorder-to-order transition upon binding of an inhibitory peptide, the intricate and highly selective extraction process of RhoGTPases is orchestrated via a dynamic ensemble bearing preformed transient structural properties, suitably modulated by the specific surrounding along the multi-step process.

Zika Virus Disease and Pregnancy Outcomes in Colombia.

BACKGROUND: In 2015 and 2016, Colombia had a widespread outbreak of Zika virus. Data from two national population-based surveillance systems for symptomatic Zika virus disease (ZVD) and birth defects provided complementary information on the effect of the Zika virus outbreak on pregnancies and infant outcomes. METHODS: We collected national surveillance data regarding cases of pregnant women with ZVD that were reported during the period from June 2015 through July 2016. The presence of Zika virus RNA was identified in a subgroup of these women on real-time reverse-transcriptase-polymerase-chain-reaction (rRT-PCR) assay. Brain or eye defects in infants and fetuses and other adverse pregnancy outcomes were identified among the women who had laboratory-confirmed ZVD and for whom data were available regarding pregnancy outcomes. We compared the nationwide prevalence of brain and eye defects during the outbreak with the prevalence both before and after the outbreak period. RESULTS: Of 18,117 pregnant women with ZVD, the presence of Zika virus was confirmed in 5926 (33%) on rRT-PCR. Of the 5673 pregnancies with laboratory-confirmed ZVD for which outcomes had been reported, 93 infants or fetuses (2%) had brain or eye defects. The incidence of brain or eye defects was higher among pregnancies in which the mother had an onset of ZVD symptoms in the first trimester than in those with an onset during the second or third trimester (3% vs. 1%). A total of 172 of 5673 pregnancies (3%) resulted in pregnancy loss; after the exclusion of pregnancies affected by birth defects, 409 of 5426 (8%) resulted in preterm birth and 333 of 5426 (6%) in low birth weight. The prevalence of brain or eye defects during the outbreak was 13 per 10,000 live births, as compared with a prevalence of 8 per 10,000 live births before the outbreak and 11 per 10,000 live births after the outbreak. CONCLUSIONS: In pregnant women with laboratory-confirmed ZVD, brain or eye defects in infants or fetuses were more common during the Zika virus outbreak than during the periods immediately before and after the outbreak. The frequency of such defects was increased among women with a symptom onset early in pregnancy. (Funded by the Colombian Instituto Nacional de Salud and the Centers for Disease Control and Prevention.).

Usefulness of dried blood spot samples for monitoring hepatitis C treatment outcome and reinfection among people who inject drugs in a test-and-treat program.

Dried blood spots (DBS) are a reliable tool to diagnose viremic hepatitis C virus (HCV) infection. We evaluated the clinical performance of a DBS-based molecular assay for the assessment of cure and reinfection after on-site treatment at a harm reduction center (HRC). Genotyping from DBS samples was also assessed to discriminate reinfection from treatment failure. People who inject drugs (PWID) from an ongoing test-and-treat pilot at the largest HRC in Barcelona were included in the study. HCV-RNA detection from DBS collected after treatment (with follow-up at 12, 36, and 60 weeks) was compared with a molecular point-of-care test using finger-stick blood (GeneXpert). Baseline and follow-up DBS samples were genotyped by NS5B sequencing or commercial real-time PCR. Among treated patients, 193 follow-up DBS samples were tested. The DBS-based assay showed 100% specificity (129/129), and sensitivity ranged from 84.4% to 96.1% according to different viral load cut-offs (from detectable to 3000 IU/mL). Sensitivity as test of cure (follow-up 12) ranged from 85.1% to 97.4%. Among the 64 patients with recurrent viremia, 10.9% had low viral loads (≤1000 IU/mL); HCV genotyping allowed us to classify 73.5% of viremic cases either as reinfection or as treatment failure. DBS samples are useful to assess cure and differentiate reinfection from relapse after HCV antiviral treatment in the real world, facilitating decentralization of treatment and posttreatment follow-up in PWID. However, a fraction of patients presented with low viral loads, limiting viremia detection and genotyping in DBS and, therefore, repeat testing is recommended.

The Role of Crystalline Intermediates in Mechanochemical Cyclorhodation Reactions Elucidated by in-Situ X-ray Powder Diffraction and Computation.

The occurrence of crystalline intermediates in mechanochemical reactions might be more widespread than previously assumed. For example, a recent study involving the acetate-assisted C-H activation of N-Heterocycles with [Cp*RhCl2 ]2 by ball milling revealed the formation of transient cocrystals between the reagents prior to the C-H activation step. However, such crystalline intermediates were only observed through stepwise intervallic ex-situ analysis, and their exact role in the C-H activation process remained unclear. In this study, we monitored the formation of discrete, stoichiometric cocrystals between benzo[h]quinoline and [Cp*RhCl2 ]2 by ball milling using in-situ synchrotron X-ray powder diffraction. This continuous analysis revealed an initial cocrystal that transformed into a second crystalline form. Computational studies showed that differences in noncovalent interactions made the [Cp*RhCl2 ]2 unit in the later-appearing cocrystal more reactive towards NaOAc. This demonstrated the advantage of cocrystal formation before the acetate-assisted metalation-deprotonation step, and how the net cooperative action of weak interactions between the reagents in mechanochemical experiments can lead to stable supramolecular assemblies, which can enhance substrate activation under ball-milling conditions. This could explain the superiority of some mechanochemical reactions, such as acetate-assisted C-H activation, compared to their solution-based counterparts.

UV-Resonance Raman Spectra of Systems in Complex Environments: A Multiscale Modeling Applied to Doxorubicin Intercalated into DNA.

UV-Resonance Raman (RR) spectroscopy is a valuable tool to study the binding of drugs to biomolecular receptors. The extraction of information at the molecular level from experimental RR spectra is made much easier and more complete thanks to the use of computational approaches, specifically tuned to deal with the complexity of the supramolecular system. In this paper, we propose a protocol to simulate RR spectra of complex systems at different levels of sophistication, by exploiting a quantum mechanics/molecular mechanics (QM/MM) approach. The approach is challenged to investigate RR spectra of a widely used chemotherapy drug, doxorubicin (DOX) intercalated into a DNA double strand. The computed results show good agreement with experimental data, thus confirming the reliability of the computational protocol.

Encapsulation of Astatide by a water cage.

A 512 cage of (H2O)20 consisting of 30 hydrogen bonds encapsulates Astatide with little geometrical distortion. The cage is marginally destabilized but the non-covalent interactions are actually strengthened. Host⋯cage interactions in the [At@(H2O)20]- cluster are anti-electrostatic, placing both negatively charged atoms in direct contact as in Atδ-⋯δ-O-Hδ+. An orbital interaction analysis reveals that explicit host⋯cage contacts are "inverted" hydrogen bonds. That is, the same type of donor→acceptor charge transfer as in hydrogen bonding, with no proton bridging the two negative charges.

Computational Insights into the Adsorption of Ligands on Gold Nanosurfaces.

We study the adsorption process of model peptides, nucleobases, and selected standard ligands on gold through the development of a computational protocol based on fully atomistic classical molecular dynamics (MD) simulations combined with umbrella sampling techniques. The specific features of the interface components, namely, the molecule, the metallic substrate, and the solvent, are taken into account through different combinations of force fields (FFs), which are found to strongly affect the results, especially changing absolute and relative adsorption free energies and trends. Overall, noncovalent interactions drive the process along the adsorption pathways. Our findings also show that a suitable choice of the FF combinations can shed light on the affinity, position, orientation, and dynamic fluctuations of the target molecule with respect to the surface. The proposed protocol may help the understanding of the adsorption process at the microscopic level and may drive the in-silico design of biosensors for detection purposes.

Regulation of DNA repair pathway choice in S and G2 phases by the NHEJ inhibitor CYREN.

Classical non-homologous end joining (cNHEJ) and homologous recombination compete for the repair of double-stranded DNA breaks during the cell cycle. Homologous recombination is inhibited during the G1 phase of the cell cycle, but both pathways are active in the S and G2 phases. However, it is unclear why cNHEJ does not always outcompete homologous recombination during the S and G2 phases. Here we show that CYREN (cell cycle regulator of NHEJ) is a cell-cycle-specific inhibitor of cNHEJ. Suppression of CYREN allows cNHEJ to occur at telomeres and intrachromosomal breaks during the S and G2 phases, and cells lacking CYREN accumulate chromosomal aberrations upon damage induction, specifically outside the G1 phase. CYREN acts by binding to the Ku70/80 heterodimer and preferentially inhibits cNHEJ at breaks with overhangs by protecting them. We therefore propose that CYREN is a direct cell-cycle-dependent inhibitor of cNHEJ that promotes error-free repair by homologous recombination during cell cycle phases when sister chromatids are present.

Development of mental health first-aid guidelines for depression: a Delphi expert consensus study in Argentina and Chile.

BACKGROUND: Depression is one of the most common mental health problems worldwide and, while prevalence rates in Latin America are relatively high, most people who meet the criteria for diagnosis do not receive treatment. Family and friends of a person with depression can play an important role in supporting a person to seek and engage with treatment. However, many people do not have the necessary skills or confidence to help. English-language mental health first aid guidelines have been developed to support people to provide such help. The aim of this study was to culturally adapt these guidelines for Chile and Argentina. METHODS: A Delphi expert consensus study was conducted with two expert panels, one of people with lived experience of depression (either their own or as a carer; n = 26) and one of health professionals (n = 29). Overall, 172 statements from the English-language guidelines were translated and compiled into a questionnaire. Participants were asked to rate statements based on how essential or important those statements were for Chile and Argentina and to suggest new statements if necessary. RESULTS: Data were obtained over two survey rounds. Consensus was achieved on 172 statements. A total of 137 statements were adopted from the English-language guidelines, whereas 35 new endorsed statements were generated from panel suggestions. There were similarities between the English-language guidelines and those for Chile and Argentina. The adapted guidelines did not include some of the items from the English-language guidelines related to commenting on a person's strengths or making judgements about their character, and also incorporated new items related to the incorporation of sociocultural considerations as causes of depression and attention to inequities in mental health. CONCLUSIONS: The significant number of new items underscores the importance of undertaking a careful process of cultural adaptation. Further research on dissemination and incorporation of the guidelines into the Mental Health First Aid training course for Chile and Argentina is still required.

Development of mental health first-aid guidelines for suicide risk: a Delphi expert consensus study in Argentina and Chile.

BACKGROUND: Suicide continues to pose a significant global public health challenge and ranks as one of the leading causes of death worldwide. Given the prevalence of suicide risk in the community, there is a significant likelihood of encountering individuals who may be experiencing suicidal thoughts or plans, creating an opening for non-health professionals to offer support. This study aims to culturally adapt the original Australian Mental Health First Aid Guidelines for suicide risk to the Chilean and Argentine context. METHODS: A two-round Delphi expert consensus study was conducted involving two panels, one comprising individuals with personal experience in suicide thoughts/attempts or caregiving for those with such experiences (n = 18), and the other consisting of professionals specialized in suicide assessment and support for individuals at risk (n = 25). They rated a total of 179 items mainly derived from guidelines developed by Australian experts and translated into Spanish (168), and new items included by the research team (11). The panel members were requested to assess each item utilizing a five-point Likert scale. During the second round, items that received moderate approval in the initial round were re-evaluated, and new items suggested by the local experts in the first round were also subjected to evaluation in the next round. Inclusion in the final guidelines required an 80% endorsement as "essential" or "important" from both panels. RESULTS: Consensus of approval was reached for 189 statements. Among these, 139 statements were derived from the English-language guidelines, while 50 locally generated statements were accepted during the second round. A significant difference from the original guideline was identified concerning the local experts' reluctance to discuss actions collaboratively with adolescents. Furthermore, the local experts proposed the inclusion of an entirely new section addressing suicide risk in older individuals, particularly focusing on suicide methods and warning signs. CONCLUSIONS: A Delphi expert consensus study was conducted to culturally adapt mental health first aid guidelines for assessing suicide risk in Chile and Argentina. This study involved professionals and individuals with lived experience. While many items were endorsed, some related to inquiring about suicide risk and autonomy, particularly for adolescents, were not. An additional section for older individuals was introduced. Future research should explore the implementation and impact of these adapted guidelines in training courses. This is vital for enhancing mental health support and implementing effective suicide prevention strategies in Chile and Argentina.

The transition state region in nonsynchronous concerted reactions.

The critical and vanishing points of the reaction force F(ξ) = -dV(ξ)/dξ yield five important coordinates (ξR, ξR* , ξTS, ξP* , ξP) along the intrinsic reaction coordinate (IRC) for a given concerted reaction or reaction step. These points partition the IRC into three well-defined regions, reactants (ξR→ξR* ), transition state (ξR* →ξP* ), and products (ξP* →ξP), with traditional roles of mostly structural changes associated with the reactants and products regions and mostly electronic activity associated with the transition state (TS) region. Following the evolution of chemical bonding along the IRC using formal descriptors of synchronicity, reaction electron flux, Wiberg bond orders, and their derivatives (or, more precisely, the intensity of the electron activity) unambiguously indicates that for nonsynchronous reactions, electron activity transcends the TS region and takes place well into the reactants and products regions. Under these circumstances, an extension of the TS region toward the reactants and products regions may occur.

Meanings and practices about work of women discharged from a psychiatric hospital of Buenos Aires province, Argentina / Significaciones y prácticas en torno al trabajo de mujeres externadas de un hospital neuropsiquiátrico de la provincia de Buenos Aires, Argentina.

Introduction: Work is central to the social inclusion of people who have had long-term psychiatric hospitalizations. In the context of the mental health care reform in Argentina, it is important to produce local knowledge about work inclusion of people discharged from psychiatric hospitals. The objective of this study was to describe the meanings and practices of women who had long-term psychiatric hospitalizations at the José A. Estéves Hospital in the Province of Buenos Aires, Argentina, regarding their inclusion in the labor market, once they return to live in the community. Methods and Materials: Descriptive mixed-methods study. The case of the Assisted Discharge and Rehabilitation Program of José A. Estéves Hospital, which accompanied 69 women in the year 2018, was analyzed. For quantitative analysis the data of the 69 women was analyzed, and for qualitative analysis a sample of nine women were interviewed. Results: 74% of women did some work after their discharge, although at the moment of the study only 33% were working. The jobs they carried out corresponded to elementary and low-competence occupational levels, mostly in a supported work program. After the psychiatric hospitalization, jobs obtained were less qualified, more informal and less exposed to the public than those held before the hospitalization. Discussion and Conclusionss: Prolonged psychiatric hospitalization is a significant break in people's work trajectories. Despite the value of work experiences after having a psychiatric hospitalization, those experiences mainly correspond to the informal sector of the economy.

Introducción: El trabajo es central para la inclusión social de personas que tuvieron internaciones psiquiátricas prolongadas. Por ello es necesario generar conocimientos locales sobre estos procesos en personas que han sido externadas, como parte de la reforma de la atención en salud mental en Argentina. Así, el objetivo de este estudio fue describir las significaciones y las prácticas de mujeres que tuvieron internaciones psiquiátricas prolongadas en el Hospital "José A. Estéves" de la Provincia de Buenos Aires, Argentina, acerca de su inclusión en el mercado laboral, a partir de su externación. Materiales y métodos: Estudio descriptivo de  tipo mixto, tomando como caso al grupo de mujeres que eran acompañadas por el Programa de Rehabilitación y Externación Asistida del Hospital "José A. Estéves", en el año 2018. Se analizaron datos cuantitativos de todo el grupo (n=69) y se realizaron entrevistas semiestructuradas con nueve señoras. Resultados: El 74% de las mujeres realizó algún trabajo desde su externación, aunque al momento del estudio, solo el 33% lo hacía. Los trabajos que desarrollaban correspondían a niveles ocupacionales elementales o de bajo nivel de competencia, mayoritariamente en un programa asistido de trabajo. Después de la internación, los trabajos obtenidos fueron menos calificados, más informales y menos expuestos al público que los desempeñados antes de la internación. Discusión y resultados: La internación psiquiátrica prolongada constituye un corte significativo en la trayectoria laboral de las personas. Pese al valor de las experiencias laborales de quienes logran conseguir un trabajo tras la internación, tales experiencias no implican, mayoritariamente, avances sobre el mercado formal.

The Role of Spike Protein Mutations in the Infectious Power of SARS-COV-2 Variants: A Molecular Interaction Perspective.

Specific S477N, N501Y, K417N, K417T, E484K mutations in the receptor binding domain (RBD) of the spike protein in the wild type SARS-COV-2 virus have resulted, among others, in the following variants: B.1.160 (20A or EU2, first reported in continental Europe), B1.1.7 (α or 20I501Y.V1, first reported in the United Kingdom), B.1.351 (ß or 20H/501Y.V2, first reported in South Africa), B.1.1.28.1 (γ or P.1 or 20J/501Y.V3, first reported in Brazil), and B.1.1.28.2 (ζ, or P.2 or 20B/S484K, also first reported in Brazil). From the analysis of a set of bonding descriptors firmly rooted in the formalism of quantum mechanics, including Natural Bond Orbitals (NBO), Quantum Theory of Atoms In Molecules (QTAIM) and highly correlated energies within the Domain Based Local Pair Natural Orbital Coupled Cluster Method (DLPNO-CCSD(T)), and from a set of computed electronic spectral patterns with environmental effects, we show that the new variants improve their ability to recognize available sites to either hydrogen bond or to form salt bridges with residues in the ACE2 receptor of the host cells. This results in significantly improved initial virus⋅⋅⋅cell molecular recognition and attachment at the microscopic level, which trigger the infectious cycle.

Initial Recognition and Attachment of the Zika Virus to Host Cells: A Molecular Dynamics and Quantum Interaction Approach.

The zika virus (ZIKV), transmitted to humans from the bites of Aedes Aegypti and Aedes Albopictus mosquitoes produces Zika fever and neurodegenerative disorders that despite affecting millions of people, most recently in Africa and the Americas, has been declared a neglected tropical disease by the World Health Organization. In this work, atomistic molecular dynamics simulations followed by rigorous analysis of the intermolecular interactions reveal crucial aspects of the initial virus⋯cell molecular recognition and attachment, events that trigger the infectious cycle. Previous experimental studies have shown that Dermatan Sulfate (DS) and Chondroitin Sulfate A (CSA), two glycosaminoglycans which are actually epimers to each other and that are structural constituents of receptors expressed in cell membranes, are the preferred anchorage sites, with a marked preference for DS. Our calculations rationalize this preference from a molecular perspective as follows: when free of the virus, DS has one sulfate group that does not participate in intramolecular strong hydrogen bonds, thus, it is readily available to interact with the envelope protein of the virus (Zika-E), then, after formation of the complexes, Zika-E⋯DS exhibits ten strong salt brides connecting the two fragments against only six salt bridges and two hydrogen bonds in Zika-E⋯CSA. Our results complement the current view of the interaction between the virus and the receptor glycosoaminoglycans revealing that the negatively charged carboxylate groups in CSA and DS are just as important as the sulfates because of the formation of equally strong salt bridges with the positively charged Arginine and Lysine aminoacids in the envelope protein of the virus.