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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 ( 1 HNMR). 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 (R f ) of A. paniculata extract at 0.74 ± 0.06 as similar to standard andrographolide R f 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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A 50-year-old male presented to us with features of diabetic ketoacidosis which was managed with adequate hydration and insulin therapy. His routine laboratory investigation revealed transaminitis, acute kidney injury and pancytopenia. Further evaluation for hematological and biochemical derangements uncovered positive dengue test (NS1 antigen and polymerase chain reaction assay). Patient distinctively reported no history of fever and remained afebrile during the course of illness. We report this case to highlight the possibility of afebrile dengue in endemic areas., (© Journal of the Association of Physicians of India 2011.)

Thrombocytopenia is common in patients with dengue virus (DENV) infections. With a focus on understanding the possible mechanism of thrombocytopenia in DENV infections we described a direct correlation between activation and depletion of platelets in patients. Our data showed a sharp decrease in platelet counts at day 4 of fever in patients. The high DENV genome copies in platelets correlated directly with the elevated platelet activation along with increased binding of complement factor C3 and IgG on their surface at day 4. Recovery in platelet count was observed on day 10 through day 6 and 8 with simultaneous decrease in platelet activation markers. Further, our in vitro data supported the above observations describing a concentration-dependent increase in platelet activation by DENV serotype-2. The high copy number of DENV2 genome in the platelet pellet correlated directly with platelet activation, microparticle generation and clot formation. Furthermore the DENV2-activated platelets were phagocytosed in large numbers by the monocytes. The DENV2-mediated lysis and clearance of platelets were abrogated in presence of platelet activation inhibitor, prostacyclin. These observations collectively suggest that platelet activation status is an important determinant of thrombocytopenia in dengue infections. A careful strategy of inactivation of platelets may rescue them from rapid destruction during DENV infections., Competing Interests: The authors declare no competing financial interests.

Dengue virus (DV) is the most widespread arbovirus, being endemic in over 100 countries, and is estimated to cause 50 million infections annually. Viral factors, such as the genetic composition of the virus strain can play a role in determining the virus virulence and subsequent clinical disease severity. Virus vector competence plays an integral role in virus transmission and is a critical factor in determining the severity and impact of DV outbreaks. Host genetic variations in immune-related genes, including the human leukocyte antigen, have also been shown to correlate with clinical disease and thus may play a role in regulating disease severity. The host's immune system, however, appears to be the primary factor in DV pathogenesis with the delicate interplay of innate and acquired immunity playing a crucial role. Although current research of DV pathogenesis has been limited by the lack of an appropriate animal model, the development of DV therapeutics has been a primary focus of research groups around the world. In the past decade advances in both the development of vaccines and anti-virals have increased in dramatically. This review summarises the current understanding of viral, vector and host factors which contribute to dengue virus pathogenesis and how this knowledge is critically important in the development of pharmaceutical interventions., (Copyright © 2012. Published by Elsevier Inc.)

Background: Co-circulation of multiple dengue virus serotypes has been reported from many parts of the world including India, however concurrent infection with more than one serotype of dengue viruses in the same individual is rarely documented. An outbreak of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) occurred in and around Delhi in 2006. This is the first report from India with high percentage of concurrent infections with different dengue virus serotypes circulating during one outbreak., Results: Acute phase sera from patients were tested for the presence of dengue virus RNA by RT-PCR assay. Of the 69 samples tested for dengue virus RNA, 48 (69.5%) were found to be positive. All the four dengue virus serotypes were found to be co-circulating in this outbreak with DENV-3 being the predominant serotype. In addition in 9 of 48 (19%) dengue virus positive samples, concurrent infection with more than one dengue virus serotype were identified., Conclusion: This is the first report in which concurrent infections with different dengue virus serotypes is being reported during an outbreak from India. Delhi is now truly hyperendemic for dengue.

Background Dengue is the most widespread arboviral disease globally. Serotyping of dengue viruses and their genotyping is important in tracing the epidemiology of the disease, monitoring trends and anticipating the possibility of outbreaks in a community. Methods This study is a retrospective analysis, based on data from a tertiary care center from Delhi, India and their correlation with reported literature on circulation and outbreaks of dengue in this region of north India since 1996, when the first virus isolation confirmed outbreak of dengue was reported by our virology laboratory (an Apex Laboratory of the National Vector Borne Disease Control Program, Government of India).Circulating serotypes of DENV were detected and identified from serum samples of suspected dengue patients with fever of 5 days duration or less, by virus isolation in cell culture and/or by real-time or conventional reverse transcription polymerase chain reaction (PCR). Representative serum samples of patients with suspected dengue with duration of fever <5 days were inoculated onto the C6/36 clone of Aedes albopictus cells, and the isolates were identified by indirect immunofluorescence using serotype-specific monoclonal antibodies. Sequencing was done for representative strains as required. Results The predominant serotypes identified were DENV 2 (1996), followed temporally by DENV 1 (1997–2002), DENV 3 (2003–2007), DENV 1 (2008–2012), DENV 2 (2013–2015), and DENV 3 (2016–2018). In 2003, Delhi became hyper-endemic for dengue, with all dengue serotypes co-circulating. Predominant serotypes continued to circulate for 3–6 years. Outbreaks occurred either in the year a serotype was re-introduced after a gap of a few years to become the predominant serotype, or in the following year; except in 2015, when there was a genotypic lineage change in a DENV 2 serotype which had been predominant since 2 years prior to the outbreak year. Conclusion Re-introduction of a dengue serotype which was out of circulation for a few years can precipitate an outbreak. Analysis of temporal patterns and close monitoring of circulating virus strains, particularly at either end of the transmission season, may help in early prediction of the trend for a given year, providing an opportunity to put in place control measures well in time. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]