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1.
Rev Med Virol ; 34(3): e2541, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38743385

RESUMO

As the mankind counters the ongoing COVID-19 pandemic by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), it simultaneously witnesses the emergence of mpox virus (MPXV) that signals at global spread and could potentially lead to another pandemic. Although MPXV has existed for more than 50 years now with most of the human cases being reported from the endemic West and Central African regions, the disease is recently being reported in non-endemic regions too that affect more than 50 countries. Controlling the spread of MPXV is important due to its potential danger of a global spread, causing severe morbidity and mortality. The article highlights the transmission dynamics, zoonosis potential, complication and mitigation strategies for MPXV infection, and concludes with suggested 'one health' approach for better management, control and prevention. Bibliometric analyses of the data extend the understanding and provide leads on the research trends, the global spread, and the need to revamp the critical research and healthcare interventions. Globally published mpox-related literature does not align well with endemic areas/regions of occurrence which should ideally have been the scenario. Such demographic and geographic gaps between the location of the research work and the endemic epicentres of the disease need to be bridged for greater and effective translation of the research outputs to pubic healthcare systems, it is suggested.


Assuntos
Bibliometria , Humanos , Surtos de Doenças/prevenção & controle , Animais , Mpox/epidemiologia , Mpox/transmissão , Mpox/prevenção & controle , Mpox/virologia , COVID-19/transmissão , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/virologia , SARS-CoV-2 , Zoonoses/epidemiologia , Zoonoses/virologia , Zoonoses/transmissão , Zoonoses/prevenção & controle , Pandemias/prevenção & controle
2.
Funct Integr Genomics ; 24(1): 16, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38242999

RESUMO

This study investigates the performance of reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for the colorimetric detection of SARS-CoV-2 using fluorometric dye, namely, calcein. The detection limit (LoD) with the N-ID1 primer set resulted in superior performance, corresponding to ~ 2 copies/reaction or ~ 0.1 copies/µL of the RNA sample. The color development can be observed by the naked eye, using an ultraviolet (UV) transilluminator or a hand-UV light without the requirement of expensive devices. The average time-to-reaction (TTR) value was 26.2 min in high-copy number samples, while it was about 50 min in rRT-PCR. A mobile application was proposed to quantify the positive and negative results based on the three-color spaces (RGB, Lab, and HSB). Compared to rRT-PCR (n = 67), this assay allows fast and sensitive visual detection of SARS-CoV-2, with high sensitivity (90.9%), selectivity (100%), and accuracy (94.03%). Besides, the assay was sensitive regardless of variants. Since this assay uses a fluorescent dye for visual observation, it can be easily adapted in RT-LAMP assays with high sensitivity. Thus, it can be utilized in low-source centers and field testing such as conferences, sports meetings, refugee camps, companies, and schools.


Assuntos
COVID-19 , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Sensibilidade e Especificidade , Concentração de Íons de Hidrogênio , RNA Viral/genética
3.
Rev Med Virol ; 33(1): e2391, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36017597

RESUMO

Several nations have recently begun to relax their public health protocols, particularly regarding the use of face masks when engaging in outdoor activities. This is because there has been a general trend towards fewer cases of coronavirus disease 2019 (COVID-19). However, new Omicron sub-variants (designated BA.4 and BA.5) have recently emerged. These two subvariants are thought to be the cause of an increase in COVID-19 cases in South Africa, the United States, and Europe. They have also begun to spread throughout Asia. They evolved from the Omicron lineage with characteristics that make them even more contagious and which allow them to circumvent immunity from a previous infection or vaccination. This article reviews a number of scientific considerations about these new variants, including their apparently reduced clinical severity.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Ásia , Europa (Continente)/epidemiologia , Saúde Pública , África do Sul
4.
BMC Infect Dis ; 24(1): 992, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39289659

RESUMO

BACKGROUND: Mpox is a severe viral zoonosis that has emerged as a public health concern due to its potential for human-to-human transmission and severe illness. Understanding its clinical manifestations is crucial for effective management and control. Several systematic reviews have assessed various manifestations of Mpox. This umbrella review synthesizes evidence on Mpox's manifestations across different organ systems. METHOD: We conducted an umbrella review, adhering to Joanna Briggs Institute (JBI) methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, focusing on systematic reviews of Mpox manifestations. We performed a literature search up to 25th September 2023, in databases like PubMed, Embase, and Web of Science. We included systematic reviews of observational studies, case reports, case series, or RCTs reporting any manifestations of Mpox in humans, focusing on a global scope. AMSTAR 2 was used to evaluate the quality of systematic reviews, and data has been synthesized in narrative and tabular manners. RESULTS: A total of 25 systematic reviews were included, uncovering diverse manifestations of Mpox, such as cutaneous, cardiovascular, oral, ophthalmic, gastrointestinal, respiratory, and pregnancy-related. Cutaneous manifestations (up to 100%) were the most prevalent, featuring lesions and rashes. Constitutional symptoms of viral illness were reported in ~ 60% to > 85% of the cases. Significant respiratory symptoms were present in ~ 50% of cases overall. Headaches were the leading neurological symptom present in > 30%. Symptoms of gastrointestinal involvement ranged from 39% (oral lesions) with decreasing frequency to low diarrhea at ~ 5%, with proctitis percentages ranging from high teens to mid-twenties. Ophthalmic manifestations (6% but with wide variations among studies). Many primary studies included in the systematic reviews consisted of case reports and case series. A wide range of manifestations across different organ systems was observed. Negative outcomes for pregnancies were reported, but evidence is limited. Adverse cardiovascular and neurological outcomes were identified, though only a few studies provided insights into these findings. CONCLUSION: Mpox exhibits diverse manifestations, impacting multiple organ systems, with substantial variations. The findings highlight the importance of ongoing, nuanced, and region-specific research and management strategies for Mpox. The reliance on case reports and series underscores the need for more high-quality, long-term studies to deepen our understanding and management of this significant public health concern.


Assuntos
Revisões Sistemáticas como Assunto , Humanos , Animais , Zoonoses/transmissão , Gravidez , Feminino
5.
BMC Infect Dis ; 24(1): 847, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39169304

RESUMO

BACKGROUND: Multisystem Inflammatory Syndrome in Children (MIS-C) associated with SARS-CoV-2 can lead to severe cardiovascular complications. Anakinra, an interleukin-1 receptor antagonist, is proposed to benefit the hyperinflammatory state of MIS-C, potentially improving cardiac function. This systematic review evaluated the effectiveness of early Anakinra administration on cardiac outcomes in children with MIS-C. METHODS: A comprehensive search across PubMed, Embase, and Web of Science until March 2024 identified studies using Anakinra to treat MIS-C with reported cardiac outcomes. Observational cohorts and clinical trials were included, with data extraction focusing on cardiac function metrics and inflammatory markers. Study quality was assessed using the Newcastle-Ottawa Scale. RESULTS: Six studies met the inclusion criteria, ranging from retrospective cohorts to prospective clinical studies, predominantly from the USA. Anakinra dosages ranged from 2.3 to 10 mg/kg based on disease severity. Several studies showed significant improvements in left ventricular ejection fraction and reductions in inflammatory markers like C-reactive protein, suggesting Anakinra's role in enhancing cardiac function and mitigating inflammation. However, findings on vasoactive support needs were mixed, and some studies did not report significant changes in acute cardiac support requirements. CONCLUSION: Early Anakinra administration shows potential for improving cardiac function and reducing inflammation in children with MIS-C, particularly those with severe manifestations. However, the existing evidence is limited by the observational nature of most studies and lacks randomized controlled trials (RCTs). Further high-quality RCTs are necessary to conclusively determine Anakinra's effectiveness and optimize its use in MIS-C management for better long-term cardiac outcomes and standardized treatment protocols.


Assuntos
COVID-19 , Proteína Antagonista do Receptor de Interleucina 1 , Síndrome de Resposta Inflamatória Sistêmica , Humanos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Criança , COVID-19/complicações , SARS-CoV-2/efeitos dos fármacos , Tratamento Farmacológico da COVID-19 , Resultado do Tratamento , Pré-Escolar
6.
BMC Infect Dis ; 24(1): 516, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783184

RESUMO

BACKGROUND: Human papillomavirus (HPV) is increasingly recognized as a significant risk factor in the development of head and neck cancers (HNCs), with varying prevalence and impact. This study aims to systematically review and analyze the prevalence of HPV in HNCs in India, providing insights into regional variations. METHODS: A comprehensive literature search was carried out using PubMed, Embase, and Web of Science up to November 10, 2023. Inclusion criteria focused on original research reporting HPV-positive cases among HNC patients in India. We used Nested-Knowledge software, for screening, and data extraction. The modified Newcastle-Ottawa Scale was used for quality assessment of included studies. We pooled the prevalence of HPV among HNC patients and performed a random-effects model meta-analysis using R software (version 4.3). RESULTS: The search yielded 33 studies, encompassing 4654 HNC patients. The pooled prevalence of HPV infection was found to be 33% (95% CI: 25.8-42.6), with notable heterogeneity (I² = 95%). Analysis of subgroups according to geographical location indicated varying prevalence rates. Specifically, the prevalence was 47% (95% CI: 32.2-62.4) in the eastern regions and 19.8% (95% CI: 10.8-33.4) in the western regions. No evidence of publication bias was detected. CONCLUSION: The observed considerable regional disparities on the prevalence of HPV in HNC patients in India emphasizes the need for integrated HPV vaccination and screening programs in public health strategies. The findings underline the necessity for further research to explore regional variations and treatment responses in HPV-associated HNCs, considering the impact of factors such as tobacco use and the potential benefits of HPV vaccination.


Assuntos
Neoplasias de Cabeça e Pescoço , Papillomavirus Humano , Infecções por Papillomavirus , Feminino , Humanos , Masculino , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/virologia , Papillomavirus Humano/genética , Papillomavirus Humano/isolamento & purificação , Índia/epidemiologia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Prevalência , Fatores de Risco
7.
Rev Med Virol ; 33(2): e2424, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36708022

RESUMO

Severe acute respiratory syndrome coronavirus 2 may inflict a post-viral condition known as post-COVID-19 syndrome (PCS) or long-COVID. Studies measuring levels of inflammatory and vascular biomarkers in blood, serum, or plasma of COVID-19 survivors with PCS versus non-PCS controls have produced mixed findings. Our review sought to meta-analyse those studies. A systematic literature search was performed across five databases until 25 June 2022, with an updated search on 1 November 2022. Data analyses were performed with Review Manager and R Studio statistical software. Twenty-four biomarkers from 23 studies were meta-analysed. Higher levels of C-reactive protein (Standardized mean difference (SMD) = 0.20; 95% CI: 0.02-0.39), D-dimer (SMD = 0.27; 95% CI: 0.09-0.46), lactate dehydrogenase (SMD = 0.30; 95% CI: 0.05-0.54), and leukocytes (SMD = 0.34; 95% CI: 0.02-0.66) were found in COVID-19 survivors with PCS than in those without PCS. After sensitivity analyses, lymphocytes (SMD = 0.30; 95% CI: 0.12-0.48) and interleukin-6 (SMD = 0.30; 95% CI: 0.12-0.49) were also significantly higher in PCS than non-PCS cases. No significant differences were noted in the remaining biomarkers investigated (e.g., ferritin, platelets, troponin, and fibrinogen). Subgroup analyses suggested the biomarker changes were mainly driven by PCS cases diagnosed via manifestation of organ abnormalities rather than symptomatic persistence, as well as PCS cases with duration of <6 than ≥6 months. In conclusion, our review pinpointed certain inflammatory and vascular biomarkers associated with PCS, which may shed light on potential new approaches to understanding, diagnosing, and treating PCS.


Assuntos
COVID-19 , Humanos , Síndrome de COVID-19 Pós-Aguda , Biomarcadores , SARS-CoV-2 , Proteína C-Reativa
8.
Mol Divers ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652365

RESUMO

Monkeypox virus (MPXV) core cysteine proteinase (CCP) is one of the major drug targets used to examine the inhibitory action of chemical moieties. In this study, an in silico technique was applied to screen 1395 anti-infective compounds to find out the potential molecules against the MPXV-CCP. The top five hits were selected after screening and processed for exhaustive docking based on the docked score of ≤ -9.5 kcal/mol. Later, the top three hits based on the exhaustive-docking score and interaction profile were selected to perform MD simulations. The overall RMSD suggested that two compounds, SC75741 and ammonium glycyrrhizinate, showed a highly stable complex with a standard deviation of 0.18 and 0.23 nm, respectively. Later, the MM/GBSA binding free energies of complexes showed significant binding strength with ΔGTOTAL from -21.59 to -15 kcal/mol. This report reported the potential inhibitory activity of SC75741 and ammonium glycyrrhizinate against MPXV-CCP by competitively inhibiting the binding of the native substrate.

9.
Chem Biodivers ; : e202400895, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39082609

RESUMO

The emergence of the human monkeypox virus (MPXV) and the lack of effective medications have necessitated the exploration of various strategies to combat its infection. This study employs a network-based approach to drug discovery, utilizing the BLASTn and phylogenetic analysis to compare the MPXV genome with those of 18 related orthopoxviruses, revealing over 75% genomic similarity. Through a literature review, 160 human-host proteins linked to MPXV and its relatives were identified, leading to the construction of a human-host protein interactome. Analysis of this interactome highlighted 39 central hub proteins, which were then examined for potential drug targets. The process successfully revealed 15 targets already approved for use with medications. Additionally, the functional enrichment analysis provided insights into potential pathways and disorders connected with these targets. Four medications, namely Baricitinib, Infliximab, Adalimumab, and Etanercept, have been identified as potential candidates for repurposing to combat MPXV. In addition, the pharmacophore-based screening identified a molecule that is comparable to Baricitinib and has the potential to be effective against MPXV. The findings of the study suggest that ZINC22060520 is a promising medication for treating MPXV infection and proposes these medications as potential options for additional experimental and clinical assessment in the battle against MPXV.

10.
Mikrochim Acta ; 191(6): 339, 2024 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-38789855

RESUMO

Loop-mediated isothermal amplification (LAMP) is a molecular diagnosis technology with the advantages of isothermal reaction conditions and high sensitivity. However, the LAMP reactions are prone to producing false-positive results and thus are usually less reliable. This study demonstrates a gold nanoparticle (AuNP)-assisted colorimetric LAMP technique for diagnosing SARS-CoV-2, which aims to overcome the false-positive results. The AuNPs were functionalized with E gene probes, specifically tailored to bind to the amplified E-gene LAMP product, using the freezing method. Varied salt concentration and AuNP/probe combinations were tested for the highest visual performance. The experiments were conducted on synthetic SARS-CoV-2 RNA (Omicron variant), as well as on clinical samples. The assay showed an exceptional sensitivity of 8.05 fg of LAMP amplicon mixture (0.537 fg/µL). The average reaction time was ~ 30 min. In conclusion, AuNP-assisted LAMP detection will not identify any potential unspecific amplification, which helps to improve the efficiency and reliability of LAMP assays in point-of-care applications. The freezing method to functionalize the AuNPs with probes simplifies the assay, which can be utilized in further diagnostic studies.


Assuntos
COVID-19 , Colorimetria , Ouro , Nanopartículas Metálicas , Técnicas de Amplificação de Ácido Nucleico , RNA Viral , SARS-CoV-2 , Ouro/química , Nanopartículas Metálicas/química , Colorimetria/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , SARS-CoV-2/genética , Humanos , COVID-19/diagnóstico , COVID-19/virologia , RNA Viral/genética , RNA Viral/análise , Congelamento , Técnicas de Diagnóstico Molecular/métodos , Limite de Detecção
11.
Arch Pharm (Weinheim) ; 357(1): e2300422, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37861276

RESUMO

Pineapple has been recognized for its potential to enhance health and well-being. This study aimed to gain molecular insights into the anti-inflammatory properties of fermented pineapple juice using multimodal computational studies. In this study, pineapple juice was fermented using Lactobacillus paracasei, and the solution underwent liquid chromatography-mass spectrometry analysis. Network pharmacology was applied to investigate compound interactions and targets. In silico methods assessed compound bioactivities. Protein-protein interactions, network topology, and enrichment analysis identified key compounds. Molecular docking explored compound-receptor interactions in inflammation regulation. Molecular dynamics simulations were conducted to confirm the stability of interactions between the identified crucial compounds and their respective receptors. The study revealed several compounds including short-chain fatty acids, peptides, dihydroxyeicosatrienoic acids, and glycerides that exhibited promising anti-inflammatory properties. Leucyl-leucyl-norleucine and Leu-Leu-Tyr exhibited robust and stable interactions with mitogen-activated protein kinase 14 and IκB kinase ß, respectively, indicating their potential as promising therapeutic agents for inflammation modulation. This proposition is grounded in the pivotal involvement of these two proteins in inflammatory signaling pathways. These findings provide valuable insights into the anti-inflammatory potential of these compounds, serving as a foundation for further experimental validation and exploration. Future studies can build upon these results to advance the development of these compounds as effective anti-inflammatory agents.


Assuntos
Ananas , Ananas/química , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Anti-Inflamatórios/farmacologia , Inflamação
12.
J Med Virol ; 95(1): e28306, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36372558

RESUMO

Monkeypox is a rare zoonotic disease caused by infection with the monkeypox virus. The disease can result in flu-like symptoms, fever, and a persistent rash. The disease is currently spreading throughout the world and prevention and treatment efforts are being intensified. Although there is no treatment that has been specifically approved for monkeypox virus infection, infected patients may benefit from using certain antiviral medications that are typically prescribed for the treatment of smallpox. The drugs are tecovirimat, brincidofovir, and cidofovir, all of which are currently in short supply due to the spread of the monkeypox virus. Resistance is also a concern, as widespread replication of the monkeypox virus can lead to mutations that produce monkeypox viruses that are resistant to the currently available treatments. This article discusses monkeypox disease, potential drug targets, and management strategies to overcome monkeypox disease. With the discovery of new drugs, it is hoped that the problem of insufficient drugs will be resolved, and it is not anticipated that drug resistance will become a major issue in the near future.


Assuntos
Mpox , Humanos , Mpox/tratamento farmacológico , Mpox/epidemiologia , Monkeypox virus/genética , Cidofovir/uso terapêutico , Antivirais/farmacologia , Antivirais/uso terapêutico , Surtos de Doenças
13.
Mol Divers ; 2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37925643

RESUMO

Marburg virus disease (MVD) is caused by the Marburg virus, a one-of-a-kind zoonotic RNA virus from the genus Filovirus. Thus, this current study employed AI-based QSAR and molecular docking-based virtual screening for identifying potential binders against the target protein (nucleoprotein (NP)) of the Marburg virus. A total of 2727 phytochemicals were used for screening, out of which the top three compounds (74977521, 90470472, and 11953909) were identified based on their predicted bioactivity (pIC50) and binding score (< - 7.4 kcal/mol). Later, MD simulation in triplicates and trajectory analysis were performed which showed that 11953909 and 74977521 had the most stable and consistent complex formations and had the most significant interactions with the highest number of hydrogen bonds. PCA (principal component analysis) and FEL (free energy landscape) analysis indicated that these compounds had favourable energy states for most of the conformations. The total binding free energy of the compounds using the MM/GBSA technique showed that 11953909 (ΔGTOTAL = - 30.78 kcal/mol) and 74977521 (ΔGTOTAL = - 30 kcal/mol) had the highest binding affinity with the protein. Overall, this in silico pipeline proposed that the phytochemicals 11953909 and 74977521 could be the possible binders of NP. This study aimed to find phytochemicals inhibiting the protein's function and potentially treating MVD.

14.
Mol Divers ; 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37531040

RESUMO

One of the emerging epidemic concerns is Monkeypox disease which is spreading globally. This disease is caused by the monkeypox virus (MPXV), with an increasing global incidence with an outbreak in 2022. One of the novel targets for monkeypox disease is thymidylate kinase, which is involved in pyrimidine metabolism. In this study, docking-based virtual screening and molecular dynamics techniques were employed in addition to the machine learning (ML) model to investigate the potential anti-viral natural small compounds to inhibit thymidylate kinase of MPXV. Several potential hits were identified through high-throughput virtual screening, and further top three candidates were selected, which ranked using the ML model. These three compounds were then examined under molecular dynamics simulation and MM/GBSA-binding free energy analysis. Among these, Chlorhexidine HCl showed high potential for binding to the thymidylate kinase with stable and consistent conformation with RMSD < 0.3 nm. The MM/GBSA analysis also showed the minimum binding free energy (ΔGTOTAL) of -62.41 kcal/mol for this compound. Overall, this study used structure-based drug design complemented by machine learning-guided ligand-based drug design to screen potential hit compounds from the anti-viral natural compound database.

15.
Mol Divers ; 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37578620

RESUMO

Tuberculosis (TB) is a global burden to humanity due to its adverse effects on health and society since time is not clearly defined. The existence of drug-resistant strains and the potential threat posed by latent tuberculosis act as strong impetuses for developing novel anti-tuberculosis drugs. In this study, various flavonoids were tested against the Mycobacterium tuberculosis (Mtb) Isocitrate Lyase (ICL), which has been identified as an authorised therapeutic target for treating Mtb infection. Using in silico drug discovery approach, a library of 241 flavonoid compounds was virtually screened against the binding pocket of the crystalline ligand, the VGX inhibitor, in the Mtb ICL protein. As a result, the top four flavonoids were selected based on binding score and were further considered for redocking and intermolecular contact profiling analysis. The global and local fluctuations in the protein and ligand structure were analysed using their root mean square deviation (RMSD) and root mean square fluctuation (RMSF) values obtained from the GROMACS generated 100 ns molecular dynamics (MD) simulation trajectories. The end-state binding free energy was also calculated using the MMPBSA approach for all the respective docked complexes. All four selected compounds exhibited considerable stability and affinity compared to control ligands, i.e. VGX inhibitor; however, Vaccarin showed the highest stability and affinity against the Mtb ICL protein active site, followed by the Genistin, Glabridin, and Corylin. Therefore, this study recommends selected flavonoids for in vitro and in vivo experimental studies to check their potency and efficacy against Mtb.

16.
Mol Divers ; 2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-36964456

RESUMO

Tuberculosis (TB), an infectious disease caused by the Mycobacterium tuberculosis (Mtb), has been responsible for the deaths of millions of individuals around the globe. A vital protein in viral pathogenesis known as resuscitation promoting factor (RpfB) has been identified as a potential therapeutic target of anti-tuberculosis drugs. This study offered an in silico process to examine possible RpfB inhibitors employing a computational drug design pipeline. In this study, a total of 1228 phytomolecules were virtually tested against the RpfB of Mtb. These phytomolecules were sourced from the NP-lib database of the MTi-OpenScreen server, and five top hits (ZINC000044404209, ZINC000059779788, ZINC000001562130, ZINC000014766825, and ZINC000043552589) were prioritized for compute intensive docking with dock score ≤ - 8.5 kcal/mole. Later, molecular dynamics (MD) simulation and principal component analysis (PCA) were used to validate these top five hits. In the list of these top five hits, the ligands ZINC000044404209, ZINC000059779788, and ZINC000043552589 showed hydrogen bond formation with the functional residue Glu292 of the RpfB protein suggesting biological significance of the binding. The RMSD study showed stable protein-ligand complexes and higher conformational consistency for the ligands ZINC000014766825, and ZINC000043552589 with RMSD 3-4 Å during 100 ns MD simulation. The overall analysis performed in the study suggested promising binding of these compounds with the RpfB protein of the Mtb at its functional site, further experimental investigation is needed to validate the computational finding.

17.
Global Health ; 19(1): 9, 2023 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-36747262

RESUMO

BACKGROUND: ASEAN (Association of Southeast Asian Nations) is composed of ten Southeast Asian countries bound by socio-cultural ties that promote regional peace and stability. South Asia, located in the southern subregion of Asia, includes nine countries sharing similarities in geographical and ethno-cultural factors. Chikungunya is one of the most significant problems in Southeast and South Asian countries. Much of the current chikungunya epidemic in Southeast Asia is caused by the emergence of a virus strain that originated in Africa and spread to Southeast Asia. Meanwhile, in South Asia, three confirmed lineages are in circulation. Given the positive correlation between research activity and the improvement of the clinical framework of biomedical research, this article aimed to examine the growth of chikungunya virus-related research in ASEAN and South Asian countries. METHODS: The Scopus database was used for this bibliometric analysis. The retrieved publications were subjected to a number of analyses, including those for the most prolific countries, journals, authors, institutions, and articles. Co-occurrence mapping of terms and keywords was used to determine the current state, emerging topics, and future prospects of chikungunya virus-related research. Bibliometrix and VOSviewer were used to analyze the data and visualize the collaboration network mapping. RESULTS: The Scopus search engine identified 1280 chikungunya-related documents published by ASEAN and South Asian countries between 1967 and 2022. According to our findings, India was the most productive country in South Asia, and Thailand was the most productive country in Southeast Asia. In the early stages of the study, researchers investigated the vectors and outbreaks of the chikungunya virus. In recent years, the development of antivirus agents has emerged as a prominent topic. CONCLUSIONS: Our study is the first to present the growth of chikungunya virus-related research in ASEAN and South Asian countries from 1967 to 2022. In this study, the evaluation of the comprehensive profile of research on chikungunya can serve as a guide for future studies. In addition, a bibliometric analysis may serve as a resource for healthcare policymakers.


Assuntos
Febre de Chikungunya , Vírus Chikungunya , Humanos , Febre de Chikungunya/epidemiologia , Sudeste Asiático/epidemiologia , Tailândia , Bibliometria , Índia
18.
Molecules ; 28(3)2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36770594

RESUMO

Despite their remarkable biosynthetic potential, Bacillus subtilis have been widely overlooked. However, their capability to withstand harsh conditions (extreme temperature, Ultraviolet (UV) and γ-radiation, and dehydration) and the promiscuous metabolites they synthesize have created increased commercial interest in them as a therapeutic agent, a food preservative, and a plant-pathogen control agent. Nevertheless, the commercial-scale availability of these metabolites is constrained due to challenges in their accessibility via synthesis and low fermentation yields. In the context of this rising in interest, we comprehensively visualized the antimicrobial peptides produced by B. subtilis and highlighted their prospective applications in various industries. Moreover, we proposed and classified these metabolites produced by the B. subtilis group based on their biosynthetic pathways and chemical structures. The biosynthetic pathway, bioactivity, and chemical structure are discussed in detail for each class. We believe that this review will spark a renewed interest in the often disregarded B. subtilis and its remarkable biosynthetic capabilities.


Assuntos
Bacillus , Bacillus subtilis/metabolismo
19.
Medicina (Kaunas) ; 59(4)2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-37109628

RESUMO

Background and Objectives. Multiple studies have evaluated the presence of bacterial contamination on cell phones in clinical settings; however, the presence and transmission of antibiotic-resistant bacteria on cell phones in the community have not been adequately elucidated. Material and Methods. A cross-sectional study was carried out to determine the presence of bacteria resistant to antibiotics on the cell phones of vendors in a Peruvian market and the associated factors. A sample of 127 vendors was obtained through stratified probabilistic sampling using a data collection form validated by experts. Cell phone samples were cultured using a standard technique, and antibiotic sensitivity was determined using the Kirby-Bauer technique. Chi-squared and Mann-Whitney U tests were used to determine factors associated with resistance in cell phone cultures. Results. Among the cell phones, 92.1% showed bacterial growth, predominantly Gram-positive bacteria (coagulase-negative staphylococci and Staphylococcus aureus), and 17% of the cultures showed resistance to at least three antibiotics evaluated. Two strains fell into the category of methicillin-resistant S. aureus, and three strains of E. coli had resistance to carbapenems. Conclusions. A short distance between customers and vendors, lack of a cell phone case, and having a cell phone with touchscreen are factors associated with antibiotic-resistant bacteria on cell phones.


Assuntos
Telefone Celular , Staphylococcus aureus Resistente à Meticilina , Humanos , Antibacterianos/farmacologia , Estudos Transversais , Escherichia coli , Peru , Bactérias
20.
Medicina (Kaunas) ; 59(6)2023 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-37374245

RESUMO

The multidrug-resistant (MDR) human immunodeficiency virus 1 (HIV-1) infection is an unmet medical need. HIV-1 capsid plays an important role at different stages of the HIV-1 replication cycle and is an attractive drug target for developing therapies against MDR HIV-1 infection. Lenacapavir (LEN) is the first-in-class HIV-1 capsid inhibitor approved by the USFDA, EMA, and Health Canada for treating MDR HIV-1 infection. This article highlights the development, pharmaceutical aspects, clinical studies, patent literature, and future directions on LEN-based therapies. The literature for this review was collected from PubMed, authentic websites (USFDA, EMA, Health Canada, Gilead, and NIH), and the free patent database (Espacenet, USPTO, and Patent scope). LEN has been developed by Gilead and is marketed as Sunlenca (tablet and subcutaneous injection). The long-acting and patient-compliant LEN demonstrated a low level of drug-related mutations, is active against MDR HIV-1 infection, and does not reveal cross-resistance to other anti-HIV drugs. LEN is also an excellent drug for patients having difficult or limited access to healthcare facilities. The literature has established additive/synergistic effects of combining LEN with rilpivirine, cabotegravir, islatravir, bictegravir, and tenofovir. HIV-1 infection may be accompanied by opportunistic infections such as tuberculosis (TB). The associated diseases make HIV treatment complex and warrant drug interaction studies (drug-drug, drug-food, and drug-disease interaction). Many inventions on different aspects of LEN have been claimed in patent literature. However, there is a great scope for developing more inventions related to the drug combination of LEN with anti-HIV/anti-TB drugs in a single dosage form, new formulations, and methods of treating HIV and TB co-infection. Additional research may provide more LEN-based treatments with favorable pharmacokinetic parameters for MDR HIV-1 infections and associated opportunistic infections such as TB.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Infecções Oportunistas , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Humanos , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Capsídeo , Antituberculosos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
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