Platelet activation determines the severity of thrombocytopenia in dengue infection

Ojha, Amrita; Nandi, Dipika; Batra, Harish; Singhal, Rashi; Annarapu, Gowtham K.; Bhattacharyya, Sankar; Seth, Tulika; Dar, Lalit; Medigeshi, Guruprasad R.; Vrati, Sudhanshu; Vikram, Naval K.; Guchhait, Prasenjit

doi:10.1038/srep41697

Cited by 145 publications

(143 citation statements)

References 32 publications

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“…Here, A129 male mice were infected with 1 ϫ 10 3 PFU of a clinical isolate of DENV-2 (strain 05K3295), resulting in elevated viral loads in serum, spleen, liver, and brain, as observed in the vehicle-treated control group, consistent with previous reports ( Fig. 7A to D) (19,(21)(22)(23). Treatment with compound 10 (10 mg/kg, intraperitoneally [i.p.…”

Section: Zandi Et Al Antimicrobial Agents and Chemotherapysupporting

confidence: 90%

Nucleoside Analogs with Selective Antiviral Activity against Dengue Fever and Japanese Encephalitis Viruses

Zandi

Bassit

Amblard

et al. 2019

Antimicrob Agents Chemother

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Dengue virus (DENV) and Japanese encephalitis virus (JEV) are important arthropod-borne viruses from the Flaviviridae family. DENV is a global public health problem with significant social and economic impacts, especially in tropical and subtropical areas. JEV is a neurotropic arbovirus endemic to east and southeast Asia. There are no U.S. FDA-approved antiviral drugs available to treat or to prevent DENV and JEV infections, leaving nearly one-third of the world's population at risk for infection. Therefore, it is crucial to discover potent antiviral agents against these viruses. Nucleoside analogs, as a class, are widely used for the treatment of viral infections. In this study, we discovered nucleoside analogs that possess potent and selective anti-JEV and anti-DENV activities across all serotypes in cell-based assay systems. Both viruses were susceptible to sugar-substituted 2=-C-methyl analogs with either cytosine or 7-deaza-7-fluoro-adenine nucleobases. Mouse studies confirmed the anti-DENV activity of these nucleoside analogs. Molecular models were assembled for DENV serotype 2 (DENV-2) and JEV RNA-dependent RNA polymerase replication complexes bound to nucleotide inhibitors. These models show similarities between JEV and DENV-2, which recognize the same nucleotide inhibitors. Collectively, our findings provide promising compounds and a structural rationale for the development of direct-acting antiviral agents with dual activity against JEV and DENV infections.KEYWORDS Dengue virus, Japanese encephalitis virus, antiviral agents, nucleoside analogs D engue virus (DENV) and Japanese encephalitis virus (JEV) are members of the genus Flavivirus, belonging to the family Flaviviridae. Many flaviviruses are arthropod borne and cause severe infections in humans and vertebrate animals. DENV has four serotypes (DENV-1 to DENV-4), which collectively pose a health threat to 2.5 billion people worldwide, with 50 million to 100 million human infections and 500,000 cases of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) annually (1-3). JEV is one of the most important neurotropic flaviviruses that causes encephalitis in humans. Symptoms range from mild febrile illness to mortal illness, especially in children, with about 67,900 cases each year (4). JEV is endemic in eastern and southern Asia (including China, Indonesia, Nepal, Thailand, Saipan Island, Pakistan, and the Torres Strait) and Australia, with fatality rates of 20% to 30% and life-long neurological impairments and sequelae among one-half of the survivors (5-8). Despite a licensed vaccine to prevent JEV infection, infections occur annually due to a lack of complete coverage and access (9). A tetravalent DENV vaccine also exists but remains partially on July 10, 2020 by guest http://aac.asm.org/ Downloaded fromArg474. The triphosphate group forms electrostatic interactions with Arg474, Lys694, and two active site Mn 2ϩ ions.Nucleoside inhibitors of DENV. The same 14 nucleoside analogs were assayed against DENV using a BHK-21 cell line harboring the...

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Section: Zandi Et Al Antimicrobial Agents and Chemotherapysupporting

confidence: 90%

Nucleoside Analogs with Selective Antiviral Activity against Dengue Fever and Japanese Encephalitis Viruses

Zandi

Bassit

Amblard

et al. 2019

Antimicrob Agents Chemother

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“…Numerous studies have shown that platelets and megakaryocytes can be infected in vitro and also that active infection of platelets has been shown to occur in patients with acute dengue . Such infection of platelets may lead to thrombocytopenia and cytokine production, and so potentially contribute to severe clinical disease …”

Section: Introductionmentioning

confidence: 99%

Pathogenesis of vascular leak in dengue virus infection

2017

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SummaryEndothelial dysfunction leading to vascular leak is the hallmark of severe dengue. Vascular leak typically becomes clinically evident 3-6 days after the onset of illness, which is known as the critical phase. This critical phase follows the period of peak viraemia, and lasts for 24-48 hr and usually shows rapid and complete reversal, suggesting that it is likely to occur as a result of inflammatory mediators, rather than infection of the endothelium. Cytokines such as tumour necrosis factor-a, which are known to be elevated in the critical phase of dengue, are likely to be contributing factors. Dengue NS1, a soluble viral protein, has also been shown to disrupt the endothelial glycocalyx and thus contribute to vascular leak, although there appears to be a discordance between the timing of NS1 antigenaemia and occurrence of vascular leak. In addition, many inflammatory lipid mediators are elevated in acute dengue viral infection such as platelet activating factor (PAF) and leukotrienes. Furthermore, many other inflammatory mediators such as vascular endothelial growth factor and angiopoietin-2 have been shown to be elevated in patients with dengue haemorrhagic fever, exerting their action in part by inducing the activity of phospholipases, which have diverse inflammatory effects including generation of PAF. Platelets have also been shown to significantly contribute to endothelial dysfunction by production of interleukin-1b through activation of the NLRP3 inflammasome and also by inducing production of inflammatory cytokines by monocytes. Drugs that block down-stream immunological mediator pathways such as PAF may also be beneficial in the treatment of severe disease.

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“…Migraine is normal to severe aching pain in head with symptoms of nausea, vomiting, sensitivity to sound (phonophobia), sensitivity to light (photophobia) and head movements. Migraines is one of the most frequently found pathologies of the central nervous system (CNS) which leads to decreased work productivity, performance and affect one Peron out of ten [50]. A new classification of migraines by the Headache Classification Committee of International Headache Society (IHS) in 2004 called "migraines with aura.'…”

Section: Ginger In Treatment Of Migrainementioning

confidence: 99%

Advancement and Future Directions towards Herbal Treatment for Various Diseases

Ghani¹,

Batool²,

Rafeeq³

et al. 2019

SJMPS

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The purpose of review article is to find herbal drug for treatment of some diseases. Several side effects came from chemical drugs. Use of non-chemical, non-invasive natural remedies have no major adverse effect because contain naturally active biological components, therefore they have paying much attention within recent years. Possible usage of leaf extract of Papaya for treatment of dengue fever promising cure for dengue patients. Pomegranate contains high level of antioxidants which make it one of the best fruits for boosting blood count. Phenolic compound extraction from extra virgin olive oil has immune modulatory and anti-inflammatory effects in Systemic lupus erythematosus (SLE) patients. Wound healing properties are exerted from aloe Vera gel. Fenugreek seed best natural remedy for Poly ovarian cyst syndrome (POCS). Garlic and ginger are organosulfur compounds consisting upon its bio actives having an important role in cardiovascular diseases and cancer respectively.Nigella sativa recently demonstrates the role in diabetes mellitus. Allium cepa. L (Onion) contain phytochemicals that have antidiabetic, anticarcinogenic, anti-inflammatory, antibiotic, antioxidant, antimicrobial and antiplatelet effects on the human health.

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Platelet activation determines the severity of thrombocytopenia in dengue infection

Cited by 145 publications

References 32 publications

Nucleoside Analogs with Selective Antiviral Activity against Dengue Fever and Japanese Encephalitis Viruses

Nucleoside Analogs with Selective Antiviral Activity against Dengue Fever and Japanese Encephalitis Viruses

Pathogenesis of vascular leak in dengue virus infection

Advancement and Future Directions towards Herbal Treatment for Various Diseases

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