scholarly journals The Serological Cross-Detection of Bat-Borne Hantaviruses: A Valid Strategy or Taking Chances?

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1188
Author(s):  
Renata Carvalho de Oliveira ◽  
Jorlan Fernandes ◽  
Elba Regina de Sampaio Lemos ◽  
Fernando de Paiva Conte ◽  
Rodrigo Nunes Rodrigues-da-Silva
Keyword(s):  
Public Health ◽  
In Silico ◽  
Data Bank ◽  
Distinct Species ◽  
Geographic Range ◽  
Ab Initio Methods ◽  
Success Rates ◽  
B Cell Epitopes ◽  
Crystallographic Structures ◽  
A Minor

Bats are hosts of a range of viruses, and their great diversity and unique characteristics that distinguish them from all other mammals have been related to the maintenance, evolution, and dissemination of these pathogens. Recently, very divergent hantaviruses have been discovered in distinct species of bats worldwide, but their association with human disease remains unclear. Considering the low success rates of detecting hantavirus RNA in bat tissues and that to date no hantaviruses have been isolated from bat samples, immunodiagnostic tools could be very helpful to understand pathogenesis, epidemiology, and geographic range of bat-borne hantaviruses. In this sense, we aimed to identify in silico immunogenic B-cell epitopes present on bat-borne hantaviruses nucleoprotein (NP) and verify if they are conserved among them and other selected members of Mammantavirinae, using a combination of (the three most used) different prediction algorithms, ELLIPRO, Discotope 2.0, and PEPITO server. To support our data, we in silico modeled 3D structures of NPs from representative members of bat-borne hantaviruses, using comparative and ab initio methods due to the absence of crystallographic structures of studied proteins or similar models in the Protein Data Bank. Our analysis demonstrated the antigenic complexity of the bat-borne hantaviruses group, showing a low sequence conservation of epitopes among members of its own group and a minor conservation degree in comparison to Orthohantavirus, with a recognized importance to public health. Our data suggest that the use of recombinant rodent-borne hantavirus NPs to cross-detect antibodies against bat- or shrew-borne viruses could underestimate the real impact of this virus in nature.

In silico Discovery of Resveratrol Analogues as Potential Agents in Treatment of Metabolic Disorders

2019 ◽  
Vol 25 (35) ◽  
pp. 3776-3783
Author(s):  
Nebojša Pavlović ◽  
Maja Đanić ◽  
Bojan Stanimirov ◽  
Svetlana Goločorbin-Kon ◽  
Karmen Stankov ◽  
...  
Keyword(s):  
In Silico ◽  
Metabolic Disorders ◽  
Partial Agonist ◽  
Aqueous Solubility ◽  
Structural Similarity ◽  
Data Bank ◽  
Docking Studies ◽  
Binding Energies ◽  
Molegro Virtual Docker ◽  
Ppar Γ

Background: Resveratrol was demonstrated to act as partial agonist of PPAR-γ receptor, which opens up the possibility for its use in the treatment of metabolic disorders. Considering the poor bioavailability of resveratrol, particularly due to its low aqueous solubility, we aimed to identify analogues of resveratrol with improved pharmacokinetic properties and higher binding affinities towards PPAR-γ. Methods: 3D structures of resveratrol and its analogues were retrieved from ZINC database, while PPAR-γ structure was obtained from Protein Data Bank. Docking studies were performed using Molegro Virtual Docker software. Molecular descriptors relevant to pharmacokinetics were calculated from ligand structures using VolSurf+ software. Results: Using structural similarity search method, 56 analogues of resveratrol were identified and subjected to docking analyses. Binding energies were ranged from -136.69 to -90.89 kcal/mol, with 16 analogues having higher affinities towards PPAR-γ in comparison to resveratrol. From the calculated values of SOLY descriptor, 23 studied compounds were shown to be more soluble in water than resveratrol. However, only two tetrahydroxy stilbene derivatives, piceatannol and oxyresveratrol, had both better solubility and affinity towards PPAR-γ. These compounds also had more favorable ADME profile, since they were shown to be more metabolically stable and wider distributed in body than resveratrol. Conclusion: Piceatannol and oxyresveratrol should be considered as potential lead compounds for further drug development. Although experimental validation of obtained in silico results is required, this work can be considered as a step toward the discovery of new natural and safe drugs in treatment of metabolic disorders.

Virtual Screening, Molecular docking and in-silico ADME-Tox analysis for identification of potential main protease (Mpro) enzyme inhibitors

2020 ◽  
Vol 18 ◽  
Author(s):  
Debadash Panigrahi ◽  
Ganesh Prasad Mishra
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
In Silico ◽  
Data Bank ◽  
Future Research ◽  
Reference Compound ◽  
Unexpected Death ◽  
Main Protease ◽  
In Silico Admet

Objective:: Recent pandemic caused by SARS-CoV-2 described in Wuhan China in December-2019 spread widely almost all the countries of the world. Corona virus (COVID-19) is causing the unexpected death of many peoples and severe economic loss in several countries. Virtual screening based on molecular docking, drug-likeness prediction, and in silico ADMET study has become an effective tool for the identification of small molecules as novel antiviral drugs to treat diseases. Methods:: In the current study, virtual screening was performed through molecular docking for identifying potent inhibitors against Mpro enzyme from the ZINC library for the possible treatment of COVID-19 pandemic. Interestingly, some compounds are identified as possible anti-covid-19 agents for future research. 350 compounds were screened based on their similarity score with reference compound X77 from ZINC data bank and were subjected to docking with crystal structure available of Mpro enzyme. These compounds were then filtered by their in silico ADME-Tox and drug-likeness prediction values. Result:: Out of these 350 screened compounds, 10 compounds were selected based on their docking score and best docked pose in comparison to the reference compound X77. In silico ADME-Tox and drug likeliness predictions of the top compounds were performed and found to be excellent results. All the 10 screened compounds showed significant binding pose with the target enzyme main protease (Mpro) enzyme and satisfactory pharmacokinetic and toxicological properties. Conclusion:: Based on results we can suggest that the identified compounds may be considered for therapeutic development against the COVID-19 virus and can be further evaluated for in vitro activity, preclinical, clinical studies and formulated in a suitable dosage form to maximize their bioavailability.

scholarly journals What makes a ‘successful’ collaborative research project between public health practitioners and academics? A mixed-methods review of funding applications submitted to a local intervention evaluation scheme

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Peter van der Graaf ◽  
Lindsay Blank ◽  
Eleanor Holding ◽  
Elizabeth Goyder
Keyword(s):  
Public Health ◽  
Health Research ◽  
Collaborative Research ◽  
Online Survey ◽  
Public Health Practice ◽  
Rapid Review ◽  
Success Rates ◽  
Evaluation Scheme ◽  
Health Practitioners ◽  
Public Health Practitioners

Abstract Background The national Public Health Practice Evaluation Scheme (PHPES) is a response-mode funded evaluation programme operated by the National Institute for Health Research School for Public Health Research (NIHR SPHR). The scheme enables public health professionals to work in partnership with SPHR researchers to conduct rigorous evaluations of their interventions. Our evaluation reviewed the learning from the first five years of PHPES (2013–2017) and how this was used to implement a revised scheme within the School. Methods We conducted a rapid review of applications and reports from 81 PHPES projects and sampled eight projects (including unfunded) to interview one researcher and one practitioner involved in each sampled project (n = 16) in order to identify factors that influence success of applications and effective delivery and dissemination of evaluations. Findings from the review and interviews were tested in an online survey with practitioners (applicants), researchers (principal investigators [PIs]) and PHPES panel members (n = 19) to explore the relative importance of these factors. Findings from the survey were synthesised and discussed for implications at a national workshop with wider stakeholders, including public members (n = 20). Results Strengths: PHPES provides much needed resources for evaluation which often are not available locally, and produces useful evidence to understand where a programme is not delivering, which can be used to formatively develop interventions. Weaknesses: Objectives of PHPES were too narrowly focused on (cost-)effectiveness of interventions, while practitioners also valued implementation studies and process evaluations. Opportunities: PHPES provided opportunities for novel/promising but less developed ideas. More funded time to develop a protocol and ensure feasibility of the intervention prior to application could increase intervention delivery success rates. Threats: There can be tensions between researchers and practitioners, for example, on the need to show the 'success’ of the intervention, on the use of existing research evidence, and the importance of generalisability of findings and of generating peer-reviewed publications. Conclusions The success of collaborative research projects between public health practitioners (PHP) and researchers can be improved by funders being mindful of tensions related to (1) the scope of collaborations, (2) local versus national impact, and (3) increasing inequalities in access to funding. Our study and comparisons with related funding schemes demonstrate how these tensions can be successfully resolved.

In silico prediction of T‐cell and B‐cell epitopes of human papillomavirus type 16 L1 protein

2021 ◽  
Author(s):  
Shahab Mahmoudvand ◽  
Somayeh Shokri ◽  
Manoochehr Makvandi ◽  
Reza Taherkhani ◽  
Mohammad Rashno ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
T Cell ◽  
B Cell ◽  
In Silico ◽  
In Silico Prediction ◽  
B Cell Epitopes ◽  
Human Papillomavirus Type 16 ◽  
L1 Protein

Will Nurses’ Work Still be Valued after the COVID-19 Pandemic?

2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Pasquot L ◽  
◽  
Giorgetta S ◽  
Keyword(s):  
Public Health ◽  
Infection Rate ◽  
Health Sector ◽  
Risk Of Infection ◽  
Initial State ◽  
Public Places ◽  
The Public ◽  
High Infection ◽  
A Minor ◽  
Second Wave

Many are the aspects we should ponder on, after 17 months from the burst of the COVID-19 pandemic, especially as nurses. Due to the numerous cuts to the public health sector in the last decades in Italy, the sanitary emergency has been a great sacrifice for health professionals, as public health was completely unprepared to withstand it. The Italian government reacted to this lack of preparation with exceptionally urgent measures. Although, these measures were implemented long after the initial state of confusion and of inappropriate management, they brought about stability and led to a containment strategy for the spread of the virus across the nation [1]. The reduction in the number of COVID-19 diagnoses was mainly achieved through social distancing. At first this was only required to a small number of communities affected by high infection rates, but was eventually extended to the rest of the country from March 2020 [2]. The national lockdown during the first COVID-19 wave (from March to May 2020), was replaced by regional lockdowns in the second wave (from November 2020). As of now, regional lockdowns are integrated by the vaccine campaign and Green Pass enforcement. In November 2020 the Italian Prime Minister at the time, issued legislative measures to enforce regional lockdowns, limiting nonessential movements, cafes, restaurants and other public places opening hours. This legislation established to classify the national territory in different levels of restriction based on the infection rate: red zones - highest risk of infection, orange zones - medium high risk and yellow zones with a minor risk of infection. A later legislation introduced the white zone for territories with the lowest risk of infection (DPCM-14th January 2021). The infection rate has been important to establish a region’s tier status; however, it is not the defining parameter anymore. A new legislation from July 2021 (n.105 - 23rd July 2021), opted to classify a region’s tier status according to the hospital bed’s occupancy rate for COVID-19 patients in intensive care and other medical areas.

scholarly journals La acelerada búsqueda de candidatos terapéuticos contra SARS-CoV-2, métodos in silico: Revisión

2020 ◽  
Vol 7 (3) ◽  
pp. 347-362
Author(s):  
Oscar Cobar ◽  
Rodrigo J. Vargas
Keyword(s):  
Protein Data Bank ◽  
In Silico ◽  
Data Bank

El reposicionamiento de fármacos como la derivatización química, que se han aplicado en los estudios de descubrimiento y diseño de fármacos contra el SARS-CoV-2, dependen del ciclo de vida del virus, las dianas moleculares identificadas y un diseño basado en su estructura e interacciones moleculares. Se realizó una revisión extensa en las bases de datos públicas e institucionales RSCB-Protein Data Bank, ZINC, NCBI (PubMed, PMC), PubChem, Science Direct e instituciones como CDC, NIH y revistas científicas especializadas sobre los avances en la búsqueda de nuevas moléculas contra el nuevo coronavirus basadas en estudios in silico, detectándose más de 40,000 publicaciones sobre SARS-CoV-2 y cerca de 200 relacionadas a dichos estudios, las consideradas más relevantes fueron analizadas e incluidas en este artículo. Su análisis evidencia el avance acelerado de las herramientas computacionales y fortaleza del diseño de fármacos asistido por computadora (in silico approach) para la generación de nuevas moléculas con posibilidad de ser activas contra COVID-19 y presenta las principales dianas moleculares sobre la que actúan estos agentes con potencial antiviral.

scholarly journals IN SILICO ANTIMALARIAL TARGET SELECTION CONSERVED IN FOUR PLASMODIUM SPECIES

2020 ◽  
Author(s):  
Oladoja AWofisayo
Keyword(s):  
Comparative Genomics ◽  
Peer Review ◽  
In Silico ◽  
Drug Targets ◽  
Homo Sapiens ◽  
Mammalian Species ◽  
Target Selection ◽  
Plasmodium Species ◽  
Data Bank ◽  
Sequence Motifs

Objectives: The need for new antimalarials drugs and drug targets is pertinent due to the emergence of drug resistant strains of the parasites. Improper target selection has resulted in therapeutic failure. The genomic/post genomic era has made possible the deciphering of the 3D crystal structures of proteins and DNA which are drug targets and are deposited in the protein data bank. Methods: Novel antimalarial targets obtained from evolutionary conserved short sequence motifs are utilised and are essential in transcription processes in the parasite. The motifs TGCATGCA, GTGCAC and GTGCGTGC were curated from experimental work, validated and analysed via phylogenomics genomics and comparative genomics. PlasmoDB blastn was applied to determine their similarity in Plasmodium vivax, knowlesi, Ovale and yoeli. The complete genome of Plasmodium falciparum vivax, knowlesi, Ovale and yoeli was downloaded from the plasmoDB and their positions determined. Results: The targets are essential, conserved in rodent and mammalian species via phylogenomics with percentage identity and similarity greater than 80%, have no similar genes in the same genome and also found to be selective in the parasites vis-à-vis the Homo sapiens via comparative genomics with 0% identity and similarity in the human genome. Conclusion: The targets reveal at the molecular and biochemical level, the vulnerable regions in the parasite while safe in human hence their choices in subsequent rationale drug discovery and design protocols. Peer Review History: Received: 18 July 2020; Revised: 1 October; Accepted: 12 October, Available online: 15 November 2020 UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewer(s) detail: Dr. Tamer ELHABIBI, ERU University, Egypt, [email protected] Dr. Soroush Sardari, Biotech Pasteur Institute of Iran, Tehran, Iran, [email protected] Comments of reviewer(s): Similar Articles: IN SILICO LIGAND-BASED 2D PHARMACOPHORE GENERATION FOR H+/K+ ATPASE INHIBITORS

scholarly journals Pharmacovigilance in Pakistan: A Peek into the Future Prospects

2021 ◽  
Vol 4 (2) ◽  
Author(s):  
Sarwat Jahan ◽  
Shumaila Zahid ◽  
Naseer Ahmed
Keyword(s):  
Public Health ◽  
Drug Monitoring ◽  
Work Force ◽  
Data Bank ◽  
National Database ◽  
Uppsala Monitoring Centre ◽  
Pharmacovigilance System ◽  
Isosorbide Mononitrate ◽  
Pharmacovigilance Centre ◽  
Drug Reactions

The dire need for drug monitoring and surveillance principles are practices governing the safety profiles of the medicines arose following the 1960’s Thalidomide disaster that resulted in phocomelia in thousands of new born babies [1]. Since then Pharmacovigilance centers have been established in the member countries, which report all the untoward drug reactions to Uppsala Monitoring Centre (UMC) that is designated to perform further investigations and global dissemination of the necessary information [2]. Currently 134 countries that are collaborating with UMC of which 96% are developed while 27% are developing countries which are lagging behind as per the unavailability of infrastructure and resources [3]. Pakistan National Pharmacovigilance Centre (PNPC) Ministry of health initiated pharmacovigilance activities in Pakistan in 1994; however a stable system could not be established owing to the unavailability of human resources as well as the infrastructure [4]. Later the suggestion for the establishment of Pakistan National Pharmacovigilance center (PNPC) was mentioned by the national drug policy in 2003 [5], however, the launch of the centre took place in 2012 following the tragic death of around 200 cardiac patients in Lahore as a result of an accidental mixing of Isosorbide mononitrate with Pyrimethamine that resulted in severe deficiency of folic acid, destroying the platelets and causing profuse internal bleeding [6,7]. In the view of the gravity of the situation, an independent authority for drug regulation (Drug regulatory authority of Pakistan – DRAP) was founded under the orders of the Pakistan Supreme Court in 2018. This authority was established for ensuring availability and safety of the medications. In order to devise an infrastructure for the post-marketing drug surveillance, DRAP in collaboration with the Pharmacopoeia of US established PNPC in the year 2017 and by 2018 Pakistan was included as a member in the UMC [8]. The centre has laid down protocols and practices for the international and national coordination and has added Pakistan 134th on the drug monitoring WHO program. Currently the PNPC is being governed by the 2012 Act of DRAP for developing, promoting and regulating the pharmacovigilance system in the country and coordination with provincial sectors to empower the hospitals to establish their own pharmacovigilance centers [9]. Future Perspectives of PNPC PNPC has come a long way still being in infancy and is setting up future goals towards development. Proper guidelines have been formed and an organized system was established by PNPC till 2018 for reporting Adverse Drug Reactions (ADRs) online. Training workshops for the members are regularly carried out to keep the work force ready and updated about the regulatory and management aspects. A regional centre of PNPC was announced to be established in Islamabad in November, 2019 [10]. PNPC has also upgraded its recording, monitoring and reporting system for ADRs via affiliation with the VigiFlow database of the country permitting maximum control locally effectively managing and analyzing the country-wide data [11]. The provincial, market authority and public health stakeholders are called for regular meetings. PNPC has composed comprehensive guidelines and legislation regarding pharmacovigilance protocols that are meant to provide legal surveillance of the activities. In the long run, the PNPC is planning for the establishment of provincial pharmacovigilance centers in each province, and the sub-regional centers and integrating them into the national database. Good practices of pharmacovigilance will utilize the obtained data to bring about safety protocols. However, a number of hurdles are still in the way. There are constraints related to logistics and legal matters as well as finances. There is a requirement of a collaborated effort by all the stake holders in the country. Healthcare professionals have a limited awareness about PNPC protocols and a reluctance to report the adverse events. The main issue is getting the healthcare workers and public normalized and used to with the reporting and surveillance system in order to cope up with the reluctance to report and awareness about the protocols. The success of this system is actually two way and it depends on the response from the reporting stake holders as much as it does on the system of the organization itself. The public health programs, hospitals and healthcare units need to be encouraged to participate in the PNPC system for proper reporting and detection of serious ADRs. Training and awareness sessions need to be conducted to form and normalize a reporting culture among heath care workers in Pakistan. Methods for assessment of severity, detection of cause and preventability of the reported ADRs, need further standardization. Furthermore, the international collaboration is still deficient as the WHO data bank does not have any adverse effect reported data from Pakistan; therefore, the gap needs to be filled as a priority. Although a lot still needs to be don e, a clear  progress has been noted in the past couple of years. With the introduction of new guidelines and strategies; route to further progress is clearly marked but the effort has to involve all the stake holders which will start by the realization and understanding of the significance and need for a properly functional pharmacovigilance system in the country.

scholarly journals BUSCA DE MOLÉCULAS COM ATIVIDADE BRONCODILATADORA NA ESPÉCIE MIKANIA GLOMERATA SPRENG EMPREGANDO FERRAMENTAS IN SILICO

2020 ◽  
Vol 6 (15) ◽  
Author(s):  
Letícia Fernandes Fraga ◽  
Leonardo Luiz Borges
Keyword(s):  
Protein Data Bank ◽  
In Silico ◽  
Data Bank ◽  
Mikania Glomerata

Este estudo tem por objetivo avaliar os principais compostos que expliquem a atividade broncodilatadora da Mikania glomerata Spreng, empregando ferramentas in silico. Os metabólitos do guaco foram levantados bibliograficamente e a codificação das moléculas para a realização das predições foi obtida no site Pubchem. Realizou-se então triagem de bioatividade com os programas SwissADME, ProToxII, PASS e Molinspiration e pesquisa de alvos, com os servidores SuperPred Webserver. Após a identificação do alvo, a estrutura selecionada foi obtida pelo site Protein Data Bank (PDB) para o docking molecular com o programa GOLD. Os metabólitos da Mikania glomerata Spreng tiveram suas propriedades físico-químicas e biológicas analisadas. Os alvos para o docking molecular foram identificados e verificados para cada composto, com suas respectivas estruturas cristalografadas no Protein Data Bank (PDB). A molécula de cumarina foi selecionada pois apresentou predição de interação com o receptor muscarínico M3 (ID: 4DAJ). O docking revelou interação da cumarina com o receptor M3, o que poderia auxiliar na explicação para os efeitos broncodilatadores desta espécie vegetal. O estudo in silico do guaco, abordado neste trabalho, elegeu a cumarina como principal metabólito ativo com possível atividade broncodilatadora presente na Mikania glomerata Spreng. O docking da cumarina mostrou ancoragem desta molécula no sítio ativo do receptor muscarínico M3 devido as atividades desta espécie, assim, este marcador poderia atuar como antagonista desse receptor, apresentando possível atividade parassimpatolítica e, portanto, broncodilatadora.

scholarly journals Oral manifestations and histopathology of minor salivary gland from patients with Sjögren's Syndrome and its diagnosis in a public health system

2016 ◽  
Vol 73 (4) ◽  
pp. 297
Author(s):  
Elizângela Cristina Barbosa ◽  
Jéssica Bruna Corrêa Lindoso ◽  
Nikeila Chacon de Oliveira Conde ◽  
Luiz Fernando Souza Passos ◽  
Sandra Lúcia Euzébio Ribeiro ◽  
...  
Keyword(s):  
Public Health ◽  
Health System ◽  
Public Health System ◽  
Minor Salivary Gland ◽  
Signs And Symptoms ◽  
Salivary Flow ◽  
Sjögren Syndrome ◽  
Sjogren Syndrome ◽  
Oral Manifestations ◽  
A Minor

Objective: to analyze the oral manifestations, sialometry and the histopathology of the minor salivary glands of patients with Sjögren Syndrome (SS) treated in a public health system and diagnosed according to European American Consensus Group (EACG) criteria. Material and Methods: the 32 patients were submitted to Shirmer test, oral cavity exam, unstimulated and stimulated salivary flow measurement and, in some cases, to the serological testing. For certain patients a minor salivary gland biopsy was carried out. Results: 10 patients were diagnosed with Sjögren Syndrome (SS), among whom: 40% were diagnosed with primary (pSS) and 60% with secondary Sjögren Syndrome (sSS). All patients diagnosed with this condition complained of xerostomia and xeropthalmia. Besides xerostomia, the most frequent oral manifestations were difficulty in swallowing, dry lips, hyperemic gums and atrophic change in tongue papillae. The average scores of the Schirmer and salivary flow tests were lower in patients with sSS. Conclusion: the oral signs and symptoms are extremely important in the multisystem involvement of the SS, which emphasizes the dental surgeon responsibility in managing these patients. The establishment of multidisciplinary diagnostic centers is of utmost importance, as well as the ability to offer more objective exams in the public health system aiming at increasing the accuracy of Sjögren Syndrome diagnosis.

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