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OBJECTIVES: i) To compare the placental human papilloma virus (HPV) deoxynucleic acid (DNA) status of preterm deliveries with full term deliveries and to identify high risk (HR) genotypes (HPV 16 and 18); and ii) To compare the perinatal outcomes of HPV positive with HPV negative pregnant women. METHODS: A case control study was carried out on 100 antenatal women with singleton live pregnancies admitted in labor ward of a tertiary care teaching hospital from April 2017 to March 2018. The two study groups were i) spontaneous preterm deliveries between 24 and 36 + 6 weeks (n=50) and ii) full term deliveries ≥37 weeks (n=50). The placental tissue was analysed for HPV DNA and HR HPV genotypes were detected by type specific primers. A comparative analysis of perinatal outcomes between HPV positive and negative women was done. RESULTS: An overall placental tissue HPV prevalence of 12% (12/100) was observed in study cohort which was not significantly different between preterm and full term deliveries (16 vs. 8%, p=0.218). HPV 16 was significantly associated with preterm births (p=0.04). Both HPV affected and non-affected women were comparable in terms of mode of delivery and neonatal outcomes. However, a statistically significant association of preterm neonatal intensive care admissions with HR HPV 16 genotype was observed (p=0.04). CONCLUSIONS: Spontaneous preterm births can be attributed to placental HPV infection, specifically HR HPV 16 genotype. This association identifies a potentially preventable cause of prematurity and its associated complications, in wake of availability of an effective vaccine.
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Infecções por Papillomavirus , Nascimento Prematuro , Estudos de Casos e Controles , DNA , Feminino , Humanos , Recém-Nascido , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Placenta , Gravidez , Nascimento Prematuro/epidemiologia , Fatores de RiscoRESUMO
The present study provides the first multiepitope vaccine construct using the 3CL hydrolase protein of SARS-CoV-2. The coronavirus 3CL hydrolase (Mpro) enzyme is essential for proteolytic maturation of the virus. This study was based on immunoinformatics and structural vaccinology strategies. The design of the multiepitope vaccine was built using helper T-cell and cytotoxic T-cell epitopes from the 3CL hydrolase protein along with an adjuvant to enhance immune response; these are joined to each other by short peptide linkers. The vaccine also carries potential B-cell linear epitope regions, B-cell discontinuous epitopes, and interferon-γ-inducing epitopes. Epitopes of the constructed multiepitope vaccine were found to be antigenic, nonallergic, nontoxic, and covering large human populations worldwide. The vaccine construct was modeled, validated, and refined by different programs to achieve a high-quality three-dimensional structure. The resulting high-quality model was applied for conformational B-cell epitope selection and docking analyses with toll-like receptor-3 for understanding the capability of the vaccine to elicit an immune response. In silico cloning and codon adaptation were also performed with the pET-19b plasmid vector. The designed multiepitope peptide vaccine may prompt the development of a vaccine to control SARS-CoV-2 infection.
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Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Proteases 3C de Coronavírus/imunologia , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , SARS-CoV-2/imunologia , Receptor 3 Toll-Like/imunologia , Sequência de Aminoácidos , Sítios de Ligação , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19/genética , Clonagem Molecular/métodos , Biologia Computacional/métodos , Proteases 3C de Coronavírus/química , Proteases 3C de Coronavírus/genética , Epitopos de Linfócito B/química , Epitopos de Linfócito B/genética , Epitopos de Linfócito T/química , Epitopos de Linfócito T/genética , Vetores Genéticos/química , Vetores Genéticos/imunologia , Antígenos HLA/química , Antígenos HLA/genética , Antígenos HLA/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Imunogenicidade da Vacina , Interferon gama/genética , Interferon gama/imunologia , Simulação de Acoplamento Molecular , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidade , Linfócitos T Citotóxicos/química , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/virologia , Linfócitos T Auxiliares-Indutores/química , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/virologia , Receptor 3 Toll-Like/química , Receptor 3 Toll-Like/genética , Interface Usuário-Computador , Vacinas de Subunidades AntigênicasRESUMO
Since emergence of the Nipah virus (NiV) in 1998 from Malaysia, the NiV virus has reappeared on different occasions causing severe infections in human population associated with high rate of mortality. NiV has been placed along with Hendra virus in genus Henipavirus of family Paramyxoviridae. Fruit bats (Genus Pteropus) are known to be natural host and reservoir of NiV. During the outbreaks from Malaysia and Singapore, the roles of pigs as intermediate host were confirmed. The infection transmitted from bats to pigs and subsequently from pigs to humans. Severe encephalitis was reported in NiV infection often associated with neurological disorders. First NiV outbreak in India occurred in Siliguri district of West Bengal in 2001, where direct transmission of the NiV virus from bats-to-human and human-to-human was reported in contrast to the role of pigs in the Malaysian NiV outbreak. Regular NiV outbreaks have been reported from Bangladesh since 2001 to 2015. The latest outbreak of NiV has been recorded in May, 2018 from Kerala, India which resulted in the death of 17 individuals. Due to lack of vaccines and effective antivirals, Nipah encephalitis poses a great threat to public health. Routine surveillance studies in the infected areas can be useful in detecting early signs of infection and help in containment of these outbreaks.
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Infecções por Henipavirus/epidemiologia , Infecções por Henipavirus/veterinária , Vírus Nipah/isolamento & purificação , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/virologia , Zoonoses/epidemiologia , Zoonoses/virologia , Animais , Ásia/epidemiologia , Quirópteros , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/veterinária , Doenças Transmissíveis Emergentes/virologia , Surtos de Doenças , Transmissão de Doença Infecciosa , Monitoramento Epidemiológico , Infecções por Henipavirus/virologia , Humanos , Análise de Sobrevida , SuínosRESUMO
Zika virus (ZIKV) is a mosquito-borne virus that was first isolated from Zika forest, Uganda, in 1947. Since its inception, major and minor outbreaks have been documented from several parts of world. Aedes spp. mosquitoes are the primary vectors of ZIKV, but the virus can also be transmitted through sexual practices, materno-fetal transmission, and blood transfusion. The clinical presentations of symptomatic ZIKV infections are similar to dengue and chikungunya, including fever, headache, arthralgia, retro-orbital pain, conjunctivitis, and rash. ZIKV often causes mild illness in the majority of cases, but in some instances, it is linked with congenital microcephaly and autoimmune disorders like Guillain-Barré syndrome. The recent Indian ZIKV outbreak suggests that the virus is circulating in the South East Asian region and may cause new outbreaks in future. At present, no specific vaccines or antivirals are available to treat ZIKV, so management and control of ZIKV infections rely mostly on preventive measures.
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Aedes/virologia , Doenças Transmissíveis Emergentes/epidemiologia , Surtos de Doenças , Complicações Infecciosas na Gravidez/virologia , Infecção por Zika virus/epidemiologia , Zika virus/fisiologia , Animais , Sudeste Asiático/epidemiologia , Doenças Transmissíveis Emergentes/prevenção & controle , Doenças Transmissíveis Emergentes/transmissão , Doenças Transmissíveis Emergentes/virologia , Feminino , Saúde Global , Síndrome de Guillain-Barré , Humanos , Microcefalia , Mosquitos Vetores/virologia , Gravidez , Saúde Pública , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologiaRESUMO
The exploration of nanoscale materials for their therapeutic potential against emerging and re-emerging infections has been increased in recent years. Silver nanoparticles (AgNPs) are known to possess antimicrobial activities against different pathogens including viruses and provide an excellent opportunity to develop new antivirals. The present study focused on biological synthesis of AgNPs from Andrographis paniculata, Phyllanthus niruri, and Tinospora cordifolia and evaluation of their antiviral properties against chikungunya virus. Synthesized plants AgNPs were characterized to assess their formation, morphology, and stability. The cytotoxicity assays in Vero cells revealed that A. paniculata AgNPs were most cytotoxic with maximum non-toxic dose (MNTD) value of 31.25 µg/mL followed by P. niruri (MNTD, 125 µg/mL) and T. cordifolia AgNPs (MNTD, 250 µg/mL). In vitro antiviral assay of AgNPs based on degree of inhibition of cytopathic effect (CPE) showed that A. paniculata AgNPs were most effective, followed by T. cordifolia and P. niruri AgNPs. The results of antiviral assay were confirmed by cell viability test using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) dye, which revealed that A. paniculata AgNPs inhibited the virus to a maximum extent. The cell viability of CHIKV-infected cells significantly increased from 25.69% to 80.76 and 66.8%, when treated with A. paniculata AgNPs at MNTD and ½MNTD, respectively. These results indicated that use of plants AgNPs as antiviral agents is feasible and could provide alternative treatment options against viral diseases which have no specific antiviral or vaccines available yet.
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Antivirais/metabolismo , Antivirais/farmacologia , Vírus Chikungunya/efeitos dos fármacos , Química Verde/métodos , Nanopartículas Metálicas , Plantas Medicinais/metabolismo , Prata/metabolismo , Andrographis/metabolismo , Animais , Chlorocebus aethiops , Testes de Sensibilidade Microbiana , Phyllanthus/metabolismo , Prata/farmacologia , Tinospora/metabolismo , Células VeroRESUMO
Dengue is one of the fairly prevalent viral infections at the world level transmitted through mosquitoes (Aedes aegypti and Aedes albopictus). Due to various environmental factors, dengue cases surged rapidly at the global level in recent decades, with 193245 cases in 2021 and an increment of 110473 cases in 2022. There is no antidote available against dengue and other flaviviruses. In the absence of a dengue vaccine or specific antiviral, medicinal plants or their products can be the only choice for its effective management. Ocimum sanctum is known as ''The Incomparable One,'' ''Mother Medicine of Nature'' and ''Queen of Herbs'' in Ayurveda, and is considered an "elixir of life" supreme in both healthcare and spiritual terms. In present study eugenol was isolated in O.sanctum. Eugenol (1-hydroxy-2-methoxy-4-allylbenzene) has been substantially responsible for its therapeutic potential. High-performance thin-layer chromatography, Fourier transform infrared spectroscopy and ultraviolet-visible spectroscopy were applied to identify the compound. The Rf value of isolated compound was same in the chromatogram (0.69 + 0.05) with compare to standard. The safe dose of plant and eugenol were found as < 31.25 µg/ml and < 15.62 µg/ml. The anti-dengue activity was assessed in C6/36 cell lines, their effect was determined through Quantitative PCR. The NMR of the isolated eugenol showed similar properties as the commercial marker compound. The eugenol and SFE extract of O. sanctum showed the inhibition of 99.28% and completely against Dengue-2, respectively. Docking study exposed that the interaction of eugenol with NS1 and NS5 dengue protein showed the binding energy as - 5.33 and - 5.75 kcal/mol, respectively. The eugenol from the O. sanctum plant has the potential to be a good source of future treatment medications for dengue illness, as well as a valuable tool in its successful management.
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Hepatitis B virus (HBV) infections are highly prevalent globally, representing a serious public health problem. The diverse modes of transmission and the burden of the chronic carrier population pose challenges to the effective management of HBV. Vaccination is the most effective preventive measure available in the current scenario. Still, HBV is one of the significant health issues in various parts of the globe due to non-response to vaccines, the high number of concealed carriers, and the lack of access and awareness. Universal vaccination programs must be scaled up in neonates, especially in the developing parts of the world, to prevent new HBV infections. Novel treatments like combinational therapy, gene silencing, and new antivirals must be available for effective management. The prolonged infection of HBV, direct and indirect, can promote the growth of hepatocellular carcinoma (HCC). The present review emphasizes the problems and probable solutions for better managing HBV infections, causal risk factors of HCC, and mechanisms of HCC.
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Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite B , Neoplasias Hepáticas , Recém-Nascido , Humanos , Carcinoma Hepatocelular/epidemiologia , Vírus da Hepatite B/genética , Neoplasias Hepáticas/epidemiologia , Vacinas contra Hepatite B , Hepatite B/complicações , Hepatite B/epidemiologia , Hepatite B Crônica/epidemiologiaRESUMO
Several infections have emerged in humans, domestic animals, wildlife, and plant populations, causing a severe problem for humanity. Since the discovery of the Monkeypox virus (Mpox) in 1958 in Copenhagen, Denmark, it has resurfaced several times, producing severe infections in humans and resulting in a significant fatality rate. Mpox is an Orthopoxvirus of the Poxviridae family. This family contains various medically important viruses. The natural reservoir of Mpox is unknown yet. Mpox might be carried by African rodents and nonhuman primates (such as monkeys). The role of monkeys has been confirmed by its various outbreaks. The infection may be transferred from unidentified wild animals to monkeys, who can then spread it to humans by crossing species barriers. In close contact, human-to-human transmission is also possible. Mpox outbreaks have been documented regularly in Central and Western Africa, but recently in 2022, it has spread to over one hundred-six countries. There is no specific treatment for it, although the smallpox vaccine, antivirals, and vaccinia immune globulin help in the effective management of Mpox. In conclusion: Monkeypox poses a severe threat to public health due to the lack of specific vaccinations and effective antivirals. Surveillance studies in affected regions can assist in the early diagnosis of disease and help to control significant outbreaks. The present review provides information on epidemiology, clinical symptoms, risk factors, diagnosis, and preventive measures of Mpox.
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Viral infections are posing a great threat to humanity for the last few years. Among these, Chikungunya which is a mosquito-borne viral infection has produced enormous epidemics around the world after been rebounded. Although this infection shows a low mortality rate, patients suffer from fever, arthralgia, and maculopapular rashes, which reduce the quality of life for several weeks to years. The currently available treatments only provide symptomatic relief based on analgesics, antipyretics, and anti-inflammatory drugs which are nonspecific without satisfactory results. Medicinal plants are a widely accepted source of new molecules for the treatment of infectious diseases including viral infections. The scientific reports, primarily focusing on the anti-chikungunya activity of plant extracts, natural origin pure compounds, and their synthetic analog published from 2011 to 2021, were selected from PubMed, Google Scholar, and Scopus by using related keywords like anti-chikungunya plants, natural antivirals for Chikungunya. The present review decodes scientific reports on medicinal plants against chikungunya virus (CHIKV) infection and demystifies the potential phytoconstituents which reveals that the screening of flavonoids containing plants and phytochemicals showing efficacy against other arbovirus infections, may prove as a potential lead for drug development against CHIKV. The present article also outlines pathogenesis, clinical aspects, molecular virology, and diagnostic approaches of CHIKV infection.
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Antivirais/farmacologia , Febre de Chikungunya/tratamento farmacológico , Vírus Chikungunya/efeitos dos fármacos , Extratos Vegetais/farmacologia , Antivirais/uso terapêutico , Humanos , Fitoterapia , Extratos Vegetais/uso terapêutico , Plantas MedicinaisRESUMO
BACKGROUNDS: Leucas cephalotes is a common ethnomedicinal plant widely used by traditional healers for the treatment of Malaria and other types of fever. Oleanolic acid and its derivatives have been reported for various types of pharmacological activities, such as anti-inflammatory, antioxidant, anticancer, hepatoprotective, anti-HIV and anti-HCV activity. METHODS: L.cephalotes plant extracts were prepared by supercritical fluid extraction (SFE) method and oleanolic acid was isolated by preparatory thin-layer chromatography. The compound was identified and characterize by using ultraviolet-visible spectroscopy (UV-VIS), Fourier transform infra-Red spectroscopy (FT-IR) and high-performance thin-layer chromatography (HPTLC). The structure of the compound was elucidated by proton nuclear magnetic resonance (1HNMR) and carbon nuclear magnetic resonance (1CNMR) and the purity checked by differential scanning calorimetry (DSC). The MTT assay was used to determine the toxicity of plant extract and oleanolic acid using a microplate reader at 595 nm. The anti-dengue activity of plant extract and oleanolic acid was tested in vitro and in silico using real-time RT-PCR. RESULTS: The optimum yield of the extract was obtained at 40 °C temperature and 15Mpa pressure. The maximum non-toxic dose (MNTD) of plant extract and oleanolic acid were found as 46.87 µg/ml and 93.75 µg/ml, respectively in C6/36 cell lines. UV spectrophotometer curve of the isolated compound was overlapped with standard oleanolic acid at 232 nm. Superimposed FT-IR structure of the isolated compound was indicated the same spectra at 3433, 2939, 2871, 1690, 1500,1463, 1387, 1250, 1209, 1137 and 656 position as per marker compound. HPTLC analysis showed the retention factor of L. cephalotes extract was 0.19 + 0.06 as similar to the standard oleanolic acid chromatogram. The NMR structure of the isolated compound was identified as similar to the marker oleanolic acid structure. DSC analysis revealed the purity of isolated oleanolic acid was 98.27% with a melting point of 311.16 °C. Real-time RT PCR results revealed that L. cephalotes supercritical extract and isolated oleanolic acid showed 100 and 99.17% inhibition against the dengue - 2 virus when treated with MNTD value of plant extract (46.87 µg/ml) and the test compound (93.75 µg/ml), respectively. The molecular study demonstrated the binding energy of oleanolic acid with NS1and NS5 (non-structural protein) were - 9.42 & -8.32Kcal/mol, respectively. CONCLUSIONS: The SFE extract L. cephalotes and its active compound, oleanolic acid inhibiting the activity of dengue-2 serotype in the in vitro and in silico assays. Thus, the L.cephalotes plant could be an excellent source for drug design for the treatment of dengue infection.
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Antivirais/farmacologia , Antivirais/uso terapêutico , Dengue/tratamento farmacológico , Ácido Oleanólico/farmacologia , Ácido Oleanólico/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Simulação por Computador , Vírus da Dengue/efeitos dos fármacos , Humanos , Técnicas In Vitro , Lamiaceae/química , Plantas Medicinais/químicaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: About 2.5 billion peoples are at risk of dengue virus and the majority of people, use traditional plant-based medicines to combat dengue. The whole plant of Andrographis paniculata used traditionally over past decades for health promotion. Andrographolide isolated from Andrographis paniculata is used as natural remedy for the treatment of various diseases in different parts of the world. Andrographolide has been reported to have antiviral activity against hepatitis B virus, hepatitis C virus, herpes simplex virus, influenza virus, chikungunya virus, dengue virus 2 and 4. AIM OF THE STUDY: The aim of the present study to isolate the andrographolide from the A. paniculata by supercritical fluid extraction technique and to characterize the isolated compound along with it anti-dengue activity against DENV-2 in vitro and in silico methods. MATERIALS AND METHODS: Supercritical extraction condition for A. paniculata was standardised to isolate andrographolide compound at definite temperature and pressure on the basis of previous study. The andrographolide was identified by using Ultraviolet-Visible Spectroscopy (UV-VIS), Fourier-Transform Infrared Spectroscopy (FT-IR) and High Performance Thin Layer Chromatography (HPTLC) and Proton Nuclear Magnetic Resonance (1HNMR). The maximum non-toxic dose of isolated andrographolide was detected by MTT assay using a micro plate reader at 595 nm. One hundred (100) copies/ml of the DENV-2 virus was used for antiviral assay in C6/36 cells lines and inhibition of virus due to andrographolide was determined by real-time PCR assay. The purity of isolated andrographolide was determined by Differential Scanning Calorimetry (DSC). The dengue NS5 receptor protein was docked with andrographolide and evaluated on the basis of the total energy and binding affinity score by Auto Dock (V4.2.6) software. RESULTS: Andrographolide, a diterpene lactone was isolated from the A. paniculata supercritical extract at 40 °C temperature and 15 Mpa pressure. UV spectrophotometer analysis revealed that the curve of andrographolide plant extract was overlapped with reference compound at 228 nm and the similar bands were detected from FT-IR spectroscopy analysis at 3315, 2917, 2849, 1673, 1462 and 1454 cm-1 in isolated and standard andrographolide. HPTLC analysis shows the retention factor (Rf) of A. paniculata extract at 0.74 ± 0.06 as similar to standard andrographolide Rf values. The purity of isolated andrographolide was 99.76%. The maximum non-toxic dose of isolated andrographolide was found as 15.62 µg/ml on the C6/36 cell line calculated by using MTT assay. The andrographolide showed the 97.23% anti-dengue activity against the dengue-2 virus in C6/36 cell lines. Results of molecular docking showed that the interaction between andrographolide and NS5 of dengue protein with the maximum binding energy as -7.35 kcal/mol. CONCLUSIONS: It is concluded that isolated andrographolide from the A. paniculata possess anti-dengue activity against dengue-2 virus as revealed from in vitro and in silico method. Due to lack of the vaccine and anti-viral agents, andrographolide extracted from A. paniculata play a major role to inhibit the dengue replication. Hence, it could be a source for drug design and help to reduce the dengue infection.
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Andrographis , Antivirais/farmacologia , Vírus da Dengue/efeitos dos fármacos , Dengue/prevenção & controle , Diterpenos/farmacologia , Inibidores Enzimáticos/farmacologia , Simulação de Acoplamento Molecular , Extratos Vegetais/farmacologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Aedes , Andrographis/química , Animais , Antivirais/química , Antivirais/isolamento & purificação , Linhagem Celular , Dengue/virologia , Vírus da Dengue/enzimologia , Vírus da Dengue/crescimento & desenvolvimento , Diterpenos/química , Diterpenos/isolamento & purificação , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Ligação Proteica , Conformação Proteica , Relação Estrutura-Atividade , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/metabolismoRESUMO
The newly emerging and re-emerging of viral contagion in the present scenario are of more extensive health concern. After a long calm of many years, an unexpected eruption of the Cat Que Virus in China is a source of our concern. Cat Que Virus is an Arbovirus and belongs to the Simbu serogroup of the Orthobunyavirus genus of the Bunyaviridae family. The Simbu serogroup is an extremely diverse group of Arbovirus. The arboviruses are causing the infection in multiple hosts including humans and various livestock. They can cause mild to life-threatening infections. Arboviruses expand their spectrum and are more observable in recent times. Human actions have the most significant geophysical impact on the environment. Changes in rainfall patterns, floods, and the risk of extreme weather events are all consequences of climate change. These events may be connected to the extension of permissive vectors, geographic ranges, and therefore provide more chance of growth and spread of potential vector. Arboviruses are responsible for the health hazard to millions of people globally. It is critical to concentrate research and surveillance on these emerging and re-emerging viruses, particularly arthropod-borne viral infections. The appropriate research and surveillance on them will help us for the development of effective control and treatment strategies and also reduce health problems. The present review summarizes the current broad outline of discovery, evolution and dispersal of this unknown virus.
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Chikungunya is a notorious viral infection, which affects a large segment of world populations in absence of vaccines and antivirals. The current study evaluates of anti-chikungunya activities of Psidium guajava leaves extract and their green synthesized silver nanoparticles. Green synthesized nanoparticles were well characterized for their size and stability by dynamic light scattering (DLS), zeta potential, scanning electron microscopy (SEM) and their functional groups were analyzed by FTIR. Maximum non-toxic doses (MNTD) of extracts and nanoparticles were analysed by using Vero cell-lines. Anti-chikungunya activities of extracts and nano-particles were determined on Vero cells and their effects on cell viability were measured by MTT assay. The P. guajava nano-particles and extracts revealed the anti-chikungunya activities in the Vero cell. The cells viability was increased by 40% and 60% as compared to the virus control, when these cells were treated with MNTD of P. guajava nano-particles and extracts, respectively. To know the reason for antiviral activity, molecular docking of phytochemicals was done against a replication essential cysteine protease (nsP2) of Chikungunya. It was found that phytochemicals; Longifollen and Quercetin showed the minimum binding energy with nsP2. P. guajava extracts can be exploited to develop an effective anti-chikungunya agent. In the absence of CHIKV vaccines and antivirals, P. guajava may be used to develop rapid, responsive, specific, and cost-effective anti-chikungunya agents. Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-021-00685-4.
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Aim: Diagnosis of osteoarticular tuberculosis (OATB) is quite challenging and there is an urgent need to design a prompt and precise diagnostic test. Methods: We developed a multi-targeted loop-mediated isothermal amplification (LAMP) assay using mpt64 (Rv1980c) and pstS1 (Rv0934) targets for the detection of Mycobacterium tuberculosis in OATB patients. Results: The sensitivities of 100 and 82.4% were obtained in confirmed (n = 10) and suspected (n = 57) OATB cases, respectively by multi-targeted LAMP with a specificity of 96.9% (n = 33). Moreover, the sensitivities attained by multi-targeted LAMP in total OATB cases were significantly higher (p < 0.05-0.01) than multiplex PCR (mpt64 + pstS1) and GeneXpert assay. Conclusion: Our LAMP is simple, reliable and cost-effective method, which may develop into an attractive diagnostic kit for early detection of OATB cases.
Lay abstract Diagnosis of osteoarticular tuberculosis (OATB) or bone and joint TB caused by Mycobacterium tuberculosis (Mtb) is quite difficult owing to the low bacterial load present in OATB specimens, and difficulty of obtaining specimens since Mtb bacilli are only present deep inside the tissues. Mostly, diagnosis of OATB relies on clinical findings and imaging, which often mimic other pus-producing microbial infections and inflammatory arthritis, while the conventional bacteriological tests (smear/culture) almost fail. Therefore, we developed a multi-targeted loop-mediated isothermal amplification (LAMP) assay for early detection of OATB cases, which showed superiority over multiplex PCR and GeneXpert assay. Overall, our LAMP is straightforward, accurate and low-cost assay that may lead to the development of a diagnostic kit for routine use.
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Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Tuberculose Osteoarticular , Humanos , Reação em Cadeia da Polimerase Multiplex , Sensibilidade e Especificidade , Tuberculose Osteoarticular/diagnósticoRESUMO
OBJECTIVE: To undertake a genome-wide association study (GWAS) to identify genetic variants for stroke in an Indian population. METHODS: In a hospital-based case-control study, 8 teaching hospitals in India recruited 4,088 participants, including 1,609 stroke cases. Imputed genetic variants were tested for association with stroke subtypes using both single-marker and gene-based tests. Association with vascular risk factors was performed with logistic regression. Various databases were searched for replication, functional annotation, and association with related traits. Status of candidate genes previously reported in the Indian population was also checked. RESULTS: Associations of vascular risk factors with stroke were similar to previous reports and show modifiable risk factors such as hypertension, smoking, and alcohol consumption as having the highest effect. Single-marker-based association revealed 2 loci for cardioembolic stroke (1p21 and 16q24), 2 for small vessel disease stroke (3p26 and 16p13), and 4 for hemorrhagic stroke (3q24, 5q33, 6q13, and 19q13) at p < 5 × 10-8. The index single nucleotide polymorphism of 1p21 is an expression quantitative trait locus (p lowest = 1.74 × 10-58) for RWDD3 involved in SUMOylation and is associated with platelet distribution width (1.15 × 10-9) and 18-carbon fatty acid metabolism (p = 7.36 × 10-12). In gene-based analysis, we identified 3 genes (SLC17A2, FAM73A, and OR52L1) at p < 2.7 × 10-6. Eleven of 32 candidate gene loci studied in an Indian population replicated (p < 0.05), and 21 of 32 loci identified through previous GWAS replicated according to directionality of effect. CONCLUSIONS: This GWAS of stroke in an Indian population identified novel loci and replicated previously known loci. Genetic variants in the SUMOylation pathway, which has been implicated in brain ischemia, were identified for association with stroke.
Assuntos
Isquemia Encefálica/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/genética , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Feminino , Estudo de Associação Genômica Ampla , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Fenótipo , Locos de Características Quantitativas , Fatores de Risco , SumoilaçãoRESUMO
"SARS-CoV2", a previously unknown strain of coronaviruses caused a severe respiratory disease called Coronavirus disease (COVID-19) which emerged from Wuhan city of China on 30 December 2019, and declared as Global health problem by World Health Organisation within a month. In less than two and half months (11 March, 2020) it was declared as a pandemic disease due to its rapid spreading ability, it covered more than 211 countries infecting around 1.7 million persons and claiming around 1.1 lakhs lives within merely 100 days of its emergence. Containment of the infection of this virus is the only available measure to control the disease as no vaccine or specific antiviral treatment is available. Confirmed detection of the virus followed by isolation of the infected person at the earliest possible is the only measure to prevent this disease. Although there are number of methods available for detection of virus and to combat this disease in the present pandemic situation, but these available diagnostic methods have their own limitations. The speedy and exponential global spread of this disease strongly urges the fast and economic diagnostics tools. Additional to the available diagnostic methods, there is a sudden surge for development of various of methods and platforms to diagnose the COVID-19. The review summarized the advantage and disadvantage of various diagnostic approaches being used presently for COVID-19, newer detection methods in developmental stage and the feasibility of advanced platforms like newer nano-sensor based on-the-spot detection technologies.
RESUMO
The emerging infection of COVID-19 was initiated from Wuhan, China, have been spread to more than 210 countries around the globe including India. The clinical symptoms of COVID-19 are very similar to other respiratory viruses. The number of laboratory-confirmed cases and associated deaths are increasing regularly in various parts of the World. Seven coronaviruses (229E, NL63, OC43, HKU1, SARS, MERS and, COVID-19) can naturally infect human beings. Out of these four (229E-CoV, NL63-CoV, OC43-CoV, HKU1-CoV) are responsible for mild upper respiratory infections, while SARS-CoV, MERS-CoV, and COVID-19 are well known for their high mortality. Few mild strains of coronaviruses are circulating in India but there is no evidence of SARS and MERS outbreaks. The COVID-19 is an emerging viral infection responsible for pandemics. Fortunately, the mortality of COVID-19 is low as compared with SARS and MERS, the majority of its cases are recovered. The death toll of COVID-19 is high even after its low mortality because COVID-19 causes a pandemic while SARS-CoV and MERS-CoV cause epidemics only. COVID-19 influenced the large segments of the world population, which led to a public health emergency of international concern, putting all health organizations on high alert. COVID-19 is the first coronavirus after Spanish Flu 1918-1919, who has extremely influenced the health system, economy, and psychology of India. The present study review is on the general continent, virology, pathogenesis, global epidemiology, clinical presentation, diagnosis, treatment and control of COVID-19 with the reference to India.
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Our health and wealth are highly influenced by a number of viruses. Dengue is one of them having a global influence in absence of vaccines and antiviral. WHO suggested that the morbidity of dengue is increasing more than 6 times from 0.5 million in 2010 to over 3.34 million in 2016, following a sharp increase in 2019. The aim of the present study is to check the in vitro and in silico anti-dengue activity of Cyamopsis tetragonoloba supercritical extract in cell lines. The optimum yield of supercritical extract was obtained 0.13 g/10 g (1.3% w/w) at 40 °C temp and 15 MPa pressure and further characterized by GC-MS. The antiviral assay was performed on C6/36 cell lines with 100 copies of dengue-2 virus and maximum non-toxic dose (31.25 µg/ml) of supercritical extract and their effect was detected by real-time RT-PCR. This study revealed that C. tetragonoloba supercritical extract inhibited the dengue-2 virus (99.9%). GC-MS analysis of C. tetragonoloba supercritical extract showed the presence of 10 compounds. The major compounds identified were Hexadecanoic acid, 15-methyl-methyl ester (24.498%); 9,12-octadecadienoyl chloride, (z,z)- (23.718%); methyl dodecanoic acid (13.228%); methyl-stearate (8.696%); Tridecanoic acid, 12-methyl-, methyl-ester (8.426%), dodecanoic acid (6.102%). The study reveals that C. tetragonoloba can be exploited to develop an effective, inexpensive, and specific anti-dengue. The molecular docking study demonstrated the binding energy of 1,2-benzenedicarboxylic acid, bis(2-methylpropyl) ester (- 4.1 kcal/mol), 9,12-octadecadienoyl chloride (z,z) (- 4.0 kcal/mol) ligands were higher than others. It is concluded that C. tetragonoloba can play a major role to inhibit dengue-2 virus.
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Chikungunya is one of the highly infectious viral disease without vaccine and anti-viral. Aim of present study is to check the anti-chikungunya activities of Zingiber officinale (Ginger) in the animal cell culture model. The medicinal plant extract was prepared from Z. officinale rhizome. Median tissue culture infective dose (TCID50) of Chikungunya virus (CHIKV) and Maximum non-toxic dose (MNTD) of Z. officinale extract was determined in Vero cell-line on the basis of cell viability followed by MTT assay. In vitro anti-chikungunya activity was performed in Vero cell-line with MNTD and half of MNTD of Z. officinale medicinal plant extract. The anti-viral effect of Z. officinale was studied by observing the cytopathic effects and cell viability measured by MTT assay. Maximum non-toxic dose of Z. officinale plant extract was found 62.5 µg/ml. During anti-chikungunya experimentation, cell viability increased to 51.05% and 35.10%, when Vero cells were pre-treated with MNTD and half of MNTD of Z. officinale extract respectively. Similarly, in co-treatment, when MNTD, half of MNTD of Z. officinale and Median tissue culture infective dose CHIKV were inoculated simultaneously, then the viability of Vero cell-line was increases by 52.90% and 49.02% respectively. The rhizome extracts of Z. officinale have high potential to treat CHIKV. Medicinal plants and their metabolites are most important sources of antimicrobial and can be utilized for the development of new drugs. In view of the rapid expansion of CHIKV at the global level, there is an urgent need to develop newer anti-chikungunya drugs.
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BACKGROUND: Acute lower respiratory tract infections (ALRI) are the major cause of morbidity and mortality in young children worldwide. Information on viral etiology in ALRI from India is limited. The aim of the present study was to develop a simple, sensitive, specific and cost effective multiplex PCR (mPCR) assay without post PCR hybridization or nested PCR steps for the detection of respiratory syncytial virus (RSV), influenza viruses, parainfluenza viruses (PIV1-3) and human metapneumovirus (hMPV). Nasopharyngeal aspirates (NPAs) were collected from children with ALRI < or = 5 years of age. The sensitivity and specificity of mPCR was compared to virus isolation by centrifugation enhanced culture (CEC) followed by indirect immunofluorescence (IIF). RESULTS: From April 2005-March 2007, 301 NPAs were collected from children attending the outpatient department or admitted to the ward of All India Institute of Medical Sciences hospital at New Delhi, India. Multiplex PCR detected respiratory viruses in 106 (35.2%) of 301 samples with 130 viruses of which RSV was detected in 61, PIV3 in 22, PIV2 in 17, hMPV in 11, PIV1 in 10 and influenza A in 9 children. CEC-IIF detected 79 viruses only. The sensitivity of mPCR was 0.1TCID50 for RSV and influenza A and 1TCID50 for hMPV, PIV1, PIV2, PIV3 and Influenza B. Mixed infections were detected in 18.8% of the children with viral infections, none detected by CEC-IIF. Bronchiolitis was significantly associated with both total viral infections and RSV infection (p < 0.05). History of ARI in family predisposed children to acquire viral infection (p > 0.05). CONCLUSION: Multiplex PCR offers a rapid, sensitive and reasonably priced diagnostic method for common respiratory viruses.