Characterising information gains and losses when collecting multiple epidemic model outputs.

BACKGROUND: Collaborative comparisons and combinations of epidemic models are used as policy-relevant evidence during epidemic outbreaks. In the process of collecting multiple model projections, such collaborations may gain or lose relevant information. Typically, modellers contribute a probabilistic summary at each time-step. We compared this to directly collecting simulated trajectories. We aimed to explore information on key epidemic quantities; ensemble uncertainty; and performance against data, investigating potential to continuously gain information from a single cross-sectional collection of model results. METHODS: We compared projections from the European COVID-19 Scenario Modelling Hub. Five teams modelled incidence in Belgium, the Netherlands, and Spain. We compared July 2022 projections by incidence, peaks, and cumulative totals. We created a probabilistic ensemble drawn from all trajectories, and compared to ensembles from a median across each model's quantiles, or a linear opinion pool. We measured the predictive accuracy of individual trajectories against observations, using this in a weighted ensemble. We repeated this sequentially against increasing weeks of observed data. We evaluated these ensembles to reflect performance with varying observed data. RESULTS: By collecting modelled trajectories, we showed policy-relevant epidemic characteristics. Trajectories contained a right-skewed distribution well represented by an ensemble of trajectories or a linear opinion pool, but not models' quantile intervals. Ensembles weighted by performance typically retained the range of plausible incidence over time, and in some cases narrowed this by excluding some epidemic shapes. CONCLUSIONS: We observed several information gains from collecting modelled trajectories rather than quantile distributions, including potential for continuously updated information from a single model collection. The value of information gains and losses may vary with each collaborative effort's aims, depending on the needs of projection users. Understanding the differing information potential of methods to collect model projections can support the accuracy, sustainability, and communication of collaborative infectious disease modelling efforts.

Challenges of Secondary Glaucoma Management Following Congenital Cataract Surgery, Penetrating Keratoplasty and Vitreoretinal Surgery.

Glaucoma is one of the world's leading causes of irreversible vision loss. It is often asymptomatic until it reaches an advanced stage, which can have a significant impact on patients' daily lives. This paper describes the case of a 50-year-old female patient who presented with acute onset of ocular pain, photophobia, and loss of visual acuity in her right eye (RE). The patient's medical history includes congenital cataracts, surgical aphakia, nystagmus, strabismus, amblyopia, and secondary glaucoma. Ophthalmological examination showed BCVA RE-hand movement, left eye (LE)-0.08 with an intraocular pressure (IOP) of 30 mmHg in RE and 16 mmHg in LE. Biomicroscopic examination of RE showed corneal graft, epithelial and endothelial edema, endothelial precipitates, corneal neovascularization, aphakia, and Ahmed valve superotemporally. Despite maximal topical and systemic treatment, Ahmed valve, and trabeculectomy, secondary glaucoma in the right eye remained refractory. Reimplantation of an Ahmed valve was performed. This resulted in a favorable outcome with increased visual acuity and controlled intraocular pressure. The combination of aphakia, penetrating keratoplasty, and secondary glaucoma is a challenge for any surgeon. It is important that both the perioperative risks and the possible complications are carefully assessed in each patient, especially if associated pathology is present.

Particular Anatomy of the Hyperopic Eye and Potential Clinical Implications.

Background and Objectives: Hyperopia is a refractive error which affects cognitive and social development if uncorrected and raises the risk of primary angle-closure glaucoma (PACG). Materials and Methods: The study included only the right eye-40 hyperopic eyes in the study group (spherical equivalent (SE) under pharmacological cycloplegia over 0.50 D), 34 emmetropic eyes in the control group (SE between -0.50 D and +0.50 D). A complete ophthalmological evaluation was performed, including autorefractometry to measure SE, and additionally we performed Ocular Response Analyser: Corneal Hysteresis (CH), Corneal Resistance Factor (CRF); specular microscopy: Endothelial cell density (CD), Cell variability (CV), Hexagonality (Hex), Aladdin biometry: Anterior Chamber Depth (ACD), Axial Length (AL), Central Corneal Thickness (CCT). IBM SPSS 26 was used for statistical analysis. Results: The mean age of the entire cohort was 22.93 years (SD ± 12.069), 66.22% being female and 33.78% male. The hyperopic eyes had significantly lower AL, ACD, higher SE, CH, CRF. In the hyperopia group, there are significant, negative correlations between CH and AL (r -0.335), CRF and AL (r -0.334), SE-AL (r -0.593), ACD and CV (r -0.528), CV and CRF (r -0.438), CH (r -0.379), and positive correlations between CCT and CH (r 0.393) or CRF (r 0.435), CD and ACD (r 0.509) or CH (0.384). Age is significantly, negatively correlated with ACD (r -0.447), CH (r -0.544), CRF (r -0.539), CD (r -0.546) and positively with CV (r 0.470). Conclusions: Our study suggests a particular biomechanical behavior of the cornea in hyperopia, in relation with morphological and endothelial parameters. Moreover, the negative correlation between age and ACD suggests a shallower anterior chamber as patients age, increasing the risk for PACG.

Benzimidazole-Triazole Hybrids as Antimicrobial and Antiviral Agents: A Systematic Review.

Bacterial infections have attracted the attention of researchers in recent decades, especially due to the special problems they have faced, such as their increasing diversity and resistance to antibiotic treatment. The emergence and development of the SARS-CoV-2 infection stimulated even more research to find new structures with antimicrobial and antiviral properties. Among the heterocyclic compounds with remarkable therapeutic properties, benzimidazoles, and triazoles stand out, possessing antimicrobial, antiviral, antitumor, anti-Alzheimer, anti-inflammatory, analgesic, antidiabetic, or anti-ulcer activities. In addition, the literature of the last decade reports benzimidazole-triazole hybrids with improved biological properties compared to the properties of simple mono-heterocyclic compounds. This review aims to provide an update on the synthesis methods of these hybrids, along with their antimicrobial and antiviral activities, as well as the structure-activity relationship reported in the literature. It was found that the presence of certain groups grafted onto the benzimidazole and/or triazole nuclei (-F, -Cl, -Br, -CF3, -NO2, -CN, -CHO, -OH, OCH3, COOCH3), as well as the presence of some heterocycles (pyridine, pyrimidine, thiazole, indole, isoxazole, thiadiazole, coumarin) increases the antimicrobial activity of benzimidazole-triazole hybrids. Also, the presence of the oxygen or sulfur atom in the bridge connecting the benzimidazole and triazole rings generally increases the antimicrobial activity of the hybrids. The literature mentions only benzimidazole-1,2,3-triazole hybrids with antiviral properties. Both for antimicrobial and antiviral hybrids, the presence of an additional triazole ring increases their biological activity, which is in agreement with the three-dimensional binding mode of compounds. This review summarizes the advances of benzimidazole triazole derivatives as potential antimicrobial and antiviral agents covering articles published from 2000 to 2023.

Corrigendum: Simulation of COVID-19 propagation scenarios in the Madrid metropolitan area.

[This corrects the article DOI: 10.3389/fpubh.2021.636023.].

Synthesis, Characterization, DFT Study and Antifungal Activities of Some Novel 2-(Phenyldiazenyl)phenol Based Azo Dyes.

In recent decades, there has been an increased interest in azo compounds with special optical and biological properties. In this work, we report the preparation of novel azo-compounds with two and three -N=N- double bonds, using the classical method of synthesis, diazotization and coupling. The compounds were characterized by 1H-NMR, 13C-NMR, FTIR, UV-VIS and fluorescence spectra. DFT calculations were employed for determining the optical parameters, polarizability α, the total static dipole moment µtot, the quadrupole moment Q and the mean first polarizability ßtot. All azo derivatives show strong fluorescence emission in solutions. The antioxidant and antifungal activities were determined and the influence of the number of azo bonds was discussed. The synthesized compounds exhibit remarkable efficiency in the growth reduction of standard and clinical isolated Candida strains, suggesting future applications as novel antifungal.

New Pyrazolo-Benzimidazole Mannich Bases with Antimicrobial and Antibiofilm Activities.

A new series of pyrazolo-benzimidazole hybrid Mannich bases were synthesized, characterized by 1H-NMR, 13C-NMR, IR, UV-Vis, MS, and elemental analysis. In vitro cytotoxicity of the new compounds studied on fibroblast cells showed that the newly synthesized pyrazolo-benzimidazole hybrid derivatives were noncytotoxic until the concentration of 1 µM and two compounds presented a high degree of biocompatibility. The antibacterial and antibiofilm activity of the newly synthesized compounds was assayed on Gram-positive Staphylococcus aureus ATCC25923, Enterococcus faecalis ATCC29212, and Gram-negative Pseudomonas aeruginosa ATCC27853, Escherichia coli ATCC25922 strains. All synthesized compounds 5a-g are more active against all three tested bacterial strains Staphylococcus aureus ATCC25923, Enterococcus faecalis ATCC29212, and Escherichia coli ATCC25922 than reference drugs (Metronidazole, Nitrofurantoin), with the exception of compounds 5d and 5g, which are less active compared to Nitrofurantoin, and all synthesized compounds 5a-g are more active against Pseudomonas aeruginosa ATCC27853 compared to reference drugs (Metronidazole, Nitrofurantoin). Compound 5f showed the best activity against Staphylococcus aureus ATCC 25923, with a MIC of 150 µg/mL and has also inhibited the biofilm formed by all the bacterial strains, having an MBIC of 310 µg/mL compared to the reference drugs (Metronidazole, Nitrofurantoin).

Pyridine Compounds with Antimicrobial and Antiviral Activities.

In the context of the new life-threatening COVID-19 pandemic caused by the SARS-CoV-2 virus, finding new antiviral and antimicrobial compounds is a priority in current research. Pyridine is a privileged nucleus among heterocycles; its compounds have been noted for their therapeutic properties, such as antimicrobial, antiviral, antitumor, analgesic, anticonvulsant, anti-inflammatory, antioxidant, anti-Alzheimer's, anti-ulcer or antidiabetic. It is known that a pyridine compound, which also contains a heterocycle, has improved therapeutic properties. The singular presence of the pyridine nucleus, or its one together with one or more heterocycles, as well as a simple hydrocarbon linker, or grafted with organic groups, gives the key molecule a certain geometry, which determines an interaction with a specific protein, and defines the antimicrobial and antiviral selectivity for the target molecule. Moreover, an important role of pyridine in medicinal chemistry is to improve water solubility due to its poor basicity. In this article, we aim to review the methods of synthesis of pyridine compounds, their antimicrobial and antiviral activities, the correlation of pharmaceutical properties with various groups present in molecules as well as the binding mode from Molecular Docking Studies.

Corneal Biomechanics - an Emerging Ocular Property with a Significant Impact.

Corneal biomechanical properties reflect the capacity of the cornea to respond to applied mechanical forces. They are an increasingly important domain in ocular pathology, correlated to the diagnosis and evolution of eye diseases such as refractive errors, glaucoma or corneal ectasias. Refractive errors constitute a significant etiology of decreased vision worldwide, with a particular impact in children. Myopic eyes significantly differ from emmetropic eyes in terms of morphology and biomechanics, with differences being reported in both adults and children. In the latter, corneal hysteresis (CH) and the corneal resistance factor (CRF) are significantly lower in myopic individuals, and both biomechanical parameters correlate with the central corneal thickness and axial length. Glaucoma is a progressive optic neuropathy that leads to thinning of the nerve fiber layer and specific visual field loss, in which intraocular pressure (IOP) is an important risk factor. There is an inverse correlation between IOP and CH - a low hysteresis is associated with a high IOP. Furthermore, CH is on average lower in primary open angle glaucoma (POAG) compared to ocular hypertension (OHT) for the same IOP. Significant correlations between CH and the thickness of the ganglion cell layer (GCL) and retinal nerve fiber layer (RNFL), in both POAG and OHT, have been described. Keratoconus is the most frequent corneal ectasia, which leads to a progressive thinning and protruding of the cornea. Biomechanical parameters are severely affected in keratoconus - usually, both CH and CRF are lower compared to normal eyes. The biomechanical behavior of the cornea modulates the evolution of several ocular pathologies. As research is ongoing, more data will enable us to apply this knowledge in diagnosing disease more efficiently and targeting the right treatment for the right patient, including refractive surgery.

The pathophysiology of Sumatriptan induced non-arteritic anterior ischemic optic neuropathy.

Objective: To report a case of a non-arteritic anterior ischemic optic neuropathy (NAAION) in a patient treated with Sumatriptan. Materials and methods: NAAION represents a severe affection that frequently determines irreversible visual acuity damage. The exact cause is yet to be identified, but is usually connected to the systemic status of the patient. We presented the case of a 53-year-old female patient who complained of visual acuity loss in her right eye, associated with inferior visual field (VF) damage. Patient history revealed migraine attacks, raised arterial blood pressure (BP), mitral valve insufficiency and dyslipidemia. Systemic treatment included Sumatriptan for migraine attacks and Bisoprolol for arterial hypertension. Results: A complete ophthalmologic examination was performed, including a visual field examination and optic coherence tomography. Interdisciplinary consults, along with inflammatory biomarkers, brain scan and cardiovascular Doppler echography were used to establish the final diagnosis. Considering the patient's history, systemic medication, clinical picture, paraclinical findings and interdisciplinary check-ups, NAAION was established as a diagnosis. Discussion: NAAION occurs more frequently after the age of 50 years old and may be associated with systemic factors such as nocturnal hypotension, diabetes, atherosclerosis, sleep apnea. In the present case, the association of medically induced nocturnal hypotension and vasoconstriction led to optic nerve ischemia. Conclusions: In a patient with multiple pathology, we must consider the systemic therapy when performing any clinical examination. Abbreviations: AAION = arteritic anterior ischemic optic neuropathy, AION = anterior ischemic optic neuropathy, BCVA = best corrected visual acuity, BP = blood pressure, CS = corticosteroid, IOP = intraocular pressure, LE = left eye, MRI = magnetic resonance imaging, NAAION = non-arteritic anterior ischemic optic neuropathy, OCT = optical coherence tomography, ON = optic nerve, OU = both eyes, RE = right eye.

Evaluation of vaccination strategies for the metropolitan area of Madrid via agent-based simulation.

OBJECTIVE: We analyse the impact of different vaccination strategies on the propagation of COVID-19 within the Madrid metropolitan area, starting on 27 December 2020 and ending in Summer of 2021. MATERIALS AND METHODS: The predictions are based on simulation using EpiGraph, an agent-based COVID-19 simulator. We first summarise the different models implemented in the simulator, then provide a comprehensive description of the vaccination model and define different vaccination strategies. The simulator-including the vaccination model-is validated by comparing its results with real data from the metropolitan area of Madrid during the third COVID-19 wave. This work considers different COVID-19 propagation scenarios for a simulated population of about 5 million. RESULTS: The main result shows that the best strategy is to vaccinate first the elderly with the two doses spaced 56 days apart; this approach reduces the final infection rate by an additional 6% and the number of deaths by an additional 3% with respect to vaccinating first the elderly at the interval recommended by the vaccine producer. The reason is the increase in the number of vaccinated individuals at any time during the simulation. CONCLUSION: The existing level of detail and maturity of EpiGraph allowed us to evaluate complex scenarios and thus use it successfully to help guide the strategy for the COVID-19 vaccination campaign of the Spanish health authorities.

Assessing population-sampling strategies for reducing the COVID-19 incidence.

As long as critical levels of vaccination have not been reached to ensure heard immunity, and new SARS-CoV-2 strains are developing, the only realistic way to reduce the infection speed in a population is to track the infected individuals before they pass on the virus. Testing the population via sampling has shown good results in slowing the epidemic spread. Sampling can be implemented at different times during the epidemic and may be done either per individual or for combined groups of people at a time. The work we present here makes two main contributions. We first extend and refine our scalable agent-based COVID-19 simulator to incorporate an improved socio-demographic model which considers professions, as well as a more realistic population mixing model based on contact matrices per country. These extensions are necessary to develop and test various sampling strategies in a scenario including the 62 largest cities in Spain; this is our second contribution. As part of the evaluation, we also analyze the impact of different parameters, such as testing frequency, quarantine time, percentage of quarantine breakers, or group testing, on sampling efficacy. Our results show that the most effective strategies are pooling, rapid antigen test campaigns, and requiring negative testing for access to public areas. The effectiveness of all these strategies can be greatly increased by reducing the number of contacts for infected individual.

Biginelli Reaction Mediated Synthesis of Antimicrobial Pyrimidine Derivatives and Their Therapeutic Properties.

Antimicrobial resistance was one of the top priorities for global public health before the start of the 2019 coronavirus pandemic (COVID-19). Moreover, in this changing medical landscape due to COVID-19, finding new organic structures with antimicrobial and antiviral properties is a priority in current research. The Biginelli synthesis that mediates the production of pyrimidine compounds has been intensively studied in recent decades, especially due to the therapeutic properties of the resulting compounds, such as calcium channel blockers, anticancer, antiviral, antimicrobial, anti-inflammatory or antioxidant compounds. In this review we aim to review the Biginelli syntheses reported recently in the literature that mediates the synthesis of antimicrobial compounds, the spectrum of their medicinal properties, and the structure-activity relationship in the studied compounds.

Synthesis of Antimicrobial Benzimidazole-Pyrazole Compounds and Their Biological Activities.

The synthesis of new compounds with antimicrobial and antiviral properties is a central objective today in the context of the COVID-19 pandemic. Benzimidazole and pyrazole compounds have remarkable biological properties, such as antimicrobial, antiviral, antitumor, analgesic, anti-inflammatory, anti-Alzheimer's, antiulcer, antidiabetic. Moreover, recent literature mentions the syntheses and antimicrobial properties of some benzimidazole-pyrazole hybrids, as well as other biological properties thereof. In this review, we aim to review the methods of synthesis of these hybrids, the antimicrobial activities of the compounds, their correlation with various groups present on the molecule, as well as their pharmaceutical properties.

Ten simple rules for making a vocabulary FAIR.

We present ten simple rules that support converting a legacy vocabulary-a list of terms available in a print-based glossary or in a table not accessible using web standards-into a FAIR vocabulary. Various pathways may be followed to publish the FAIR vocabulary, but we emphasise particularly the goal of providing a globally unique resolvable identifier for each term or concept. A standard representation of the concept should be returned when the individual web identifier is resolved, using SKOS or OWL serialised in an RDF-based representation for machine-interchange and in a web-page for human consumption. Guidelines for vocabulary and term metadata are provided, as well as development and maintenance considerations. The rules are arranged as a stepwise recipe for creating a FAIR vocabulary based on the legacy vocabulary. By following these rules you can achieve the outcome of converting a legacy vocabulary into a standalone FAIR vocabulary, which can be used for unambiguous data annotation. In turn, this increases data interoperability and enables data integration.

Antibacterial and Photocatalytic Properties of ZnO Nanoparticles Obtained from Chemical versus Saponaria officinalis Extract-Mediated Synthesis.

In the present work, the properties of ZnO nanoparticles obtained using an eco-friendly synthesis (biomediated methods in microwave irradiation) were studied. Saponaria officinalis extracts were used as both reducing and capping agents in the green nanochemistry synthesis of ZnO. Inorganic zinc oxide nanopowders were successfully prepared by a modified hydrothermal method and plant extract-mediated method. The influence of microwave irradiation was studied in both cases. The size, composition, crystallinity and morphology of inorganic nanoparticles (NPs) were investigated using dynamic light scattering (DLS), powder X-ray diffraction (XRD), SEM-EDX microscopy. Tunings of the nanochemistry reaction conditions (Zn precursor, structuring agent), ZnO NPs with various shapes were obtained, from quasi-spherical to flower-like. The optical properties and photocatalytic activity (degradation of methylene blue as model compound) were also investigated. ZnO nanopowders' antibacterial activity was tested against Gram-positive and Gram-negative bacterial strains to evidence the influence of the vegetal extract-mediated synthesis on the biological activity.

Simulation of COVID-19 Propagation Scenarios in the Madrid Metropolitan Area.

This work presents simulation results for different mitigation and confinement scenarios for the propagation of COVID-19 in the metropolitan area of Madrid. These scenarios were implemented and tested using EpiGraph, an epidemic simulator which has been extended to simulate COVID-19 propagation. EpiGraph implements a social interaction model, which realistically captures a large number of characteristics of individuals and groups, as well as their individual interconnections, which are extracted from connection patterns in social networks. Besides the epidemiological and social interaction components, it also models people's short and long-distance movements as part of a transportation model. These features, together with the capacity to simulate scenarios with millions of individuals and apply different contention and mitigation measures, gives EpiGraph the potential to reproduce the COVID-19 evolution and study medium-term effects of the virus when applying mitigation methods. EpiGraph, obtains closely aligned infected and death curves related to the first wave in the Madrid metropolitan area, achieving similar seroprevalence values. We also show that selective lockdown for people over 60 would reduce the number of deaths. In addition, evaluate the effect of the use of face masks after the first wave, which shows that the percentage of people that comply with mask use is a crucial factor for mitigating the infection's spread.

Synthesis, density functional theory study and in vitro antimicrobial evaluation of new benzimidazole Mannich bases.

The tri-component synthesis of novel chiral benzimidazole Mannich bases, by reaction between benzimidazole, aqueous 30% formaldehyde and an amine, the biological evaluation and DFT studies of the new compounds are reported here. The 1H-NMR, 13C-NMR, FTIR spectra and elemental analysis confirm the structures of the new compounds. All synthesized compounds were screened by qualitative and quantitative methods for their in vitro antibacterial activity against 4 bacterial strains. DFT studies were accomplished using GAMESS 2012 software and HOMO-LUMO analysis allowed the calculation of electronic and structural parameters of the chiral Mannich bases. The geometry of 1-methylpiperazine, the cumulated Mullikan atomic charges of the two heteroatoms and of the methyl, and the value of the global electrophilicity index (ω = 0.0527) of the M-1 molecule is correlated with its good antimicrobial activity. It was found that the presence of saturated heterocycles from the amine molecule, 1-methyl piperazine and morpholine, respectively, contributes to an increased biological activity, compared to aromatic amino analogs, diphenylamino-, 4-nitroamino- and 4-aminobenzoic acid. The planarity of the molecules, specific bond lengths and localization of HOMO-LUMO orbitals is responsible for the best biological activities of the compounds.

Evaluating the impact of the weather conditions on the influenza propagation.

BACKGROUND: Predicting the details of how an epidemic evolves is highly valuable as health institutions need to better plan towards limiting the infection propagation effects and optimizing their prediction and response capabilities. Simulation is a cost- and time-effective way of predicting the evolution of the infection as the joint influence of many different factors: interaction patterns, personal characteristics, travel patterns, meteorological conditions, previous vaccination, etc. The work presented in this paper extends EpiGraph, our influenza epidemic simulator, by introducing a meteorological model as a modular component that interacts with the rest of EpiGraph's modules to refine our previous simulation results. Our goal is to estimate the effects of changes in temperature and relative humidity on the patterns of epidemic influenza based on data provided by the Spanish Influenza Sentinel Surveillance System (SISSS) and the Spanish Meteorological Agency (AEMET). METHODS: Our meteorological model is based on the regression model developed by AB and JS, and it is tuned with influenza surveillance data obtained from SISSS. After pre-processing this data to clean it and reconstruct missing samples, we obtain new values for the reproduction number of each urban region in Spain, every 10 minutes during 2011. We simulate the propagation of the influenza by setting the date of the epidemic onset and the initial influenza-illness rates for each urban region. RESULTS: We show that the simulation results have the same propagation shape as the weekly influenza rates as recorded by SISSS. We perform experiments for a realistic scenario based on actual meteorological data from 2010-2011, and for synthetic values assumed under simplified predicted climate change conditions. Results show that a diminishing relative humidity of 10% produces an increment of about 1.6% in the final infection rate. The effect of temperature changes on the infection spread is also noticeable, with a decrease of 1.1% per extra degree. CONCLUSIONS: Using a tool like ours could help predict the shape of developing epidemics and its peaks, and would permit to quickly run scenarios to determine the evolution of the epidemic under different conditions. We make EpiGraph source code and epidemic data publicly available.

Recent advances in the use of benzimidazoles as corrosion inhibitors.

BACKGROUND: Benzimidazole, a key heterocycle in therapeutic chemistry, and its derivatives, are recently mentioned in the literature as corrosion inhibitors for steels (CS, MS), pure metals (Fe, Al, Cu, Zn) and alloys. Benzimidazoles are good corrosion inhibitors for extremely aggressive, corrosive acidic media such as 1 M HCl, 1 M HNO3, 1.5 M H2SO4, basic media, 0.1 M NaOH or salt solutions. Benzimidazole derivatives act as mixed type inhibitors, exhibiting stronger inhibitive effect on the cathodic reaction than on the anodic one. CONCLUSION: These review highlights recent research in the field of benzimidazole compounds that their role as corrosion inhibitors, the structure of the compounds, electrochemical studies, the experimental conditions, the proposed mechanisms as well as the quantum theoretical studies that predict the structure of the compounds with inhibition properties.