Anuja Krishnan

Dengue infection remains a major global public health challenge, with no specific antiviral therapy currently available. The dengue virus non-structural protein 1 (NS1) exists in both intracellular and secreted forms playing a pivotal role in viral replication, immune evasion, and pathogenesis, particularly by contributing to endothelial disruption and vascular leakage during severe disease, thereby making it a promising therapeutic target. In silico screening identified berberine, betulinic acid, and ursolic acid as top candidates, exhibiting high binding affinities and stable interactions within the NS1 binding pocket. These computational predictions were further validated by biophysical assays, which demonstrated strong and specific binding interactions between the purified NS1 protein and the selected compounds. All three compounds significantly reduced viral genome levels, with the highest inhibition observed for berberine (60%), and followed by betulinic acid (40%) and ursolic acid (28%). Consistently, berberine showed the most potent inhibition of both intracellular and extracellular NS1. Overall, these findings highlight the inhibitory potential of natural compounds against DENV NS1 and provide a strong foundation for the development of NS1-targeted antivirals as a novel therapeutic strategy against dengue infection.

Survivin, an anti-apoptotic protein, plays a pivotal role in cancer progression by disrupting the balance between cell division and apoptosis. We have developed and characterized an anti-Survivin vaccine designed as a triple fusion protein to enhance immunogenicity. In this study, we have evaluated the vaccine’s efficacy in reducing tumor growth using a Survivin expressing 4T1 pre-clinical mouse model of triple-negative breast cancer (TNBC), which is difficult to treat due to its heterogeneous microenvironment, aggressive nature, poor prognosis, and high relapse rates. The recombinant _DCSurvivin-LTB protein was purified, adsorbed onto alum, and formulated with Mycobacterium indicus pranii (MIP) before administration to Balb/c mice for dose optimization. The dose that maximized antibody production was selected for efficacy studies in 4T1 tumor-bearing mice in vivo. Vaccination elicited a strong anti-Survivin antibody response and significantly inhibited tumor growth compared with controls. Elevated Granzyme B levels in vaccinated mice indicated activation of the apoptotic pathway, contributing to tumor inhibition. IFN-γ, IL-2 and IL-12 levels were also higher after the vaccination which boosted the immune system to target the cancer cells. Histopathological analysis revealed no observable toxicity or adverse effects on major organs. Immunohistochemical analysis confirmed reduced expression of angiogenesis marker VEGF and increased expression of apoptotic marker Caspase 3. These findings highlight the potential of _DCSurvivin-LTB, in combination with MIP, as a promising immunotherapeutic approach for the treatment of metastatic TNBC expressing Survivin.

Clinical manifestation of dengue disease ranges from asymptomatic, febrile fever without warning sign (DOS) to serious outcome dengue with warning sign (DWS) and severe disease (SD) leading to shock syndrome and death. The role of antibody response in natural dengue infection is complex and not completely understood. Here, we aimed to assess serological marker for disease severity. Antibody response of dengue‐confirmed pediatric patients with acute secondary infection were evaluated against infecting virus, immature virus, and recombinant envelop protein. Immature virus antibody titers were significantly higher in DWS as compared to DOS (p = 0.0006). However, antibody titers against recombinant envelop protein were higher in DOS as compared to DWS, and antibody avidity was significantly higher against infecting virus in DOS. Serum samples of DOS patients displayed higher in vitro neutralization potential in plaque assay as compared to DWS, whereas DWS serum samples showed higher antibody‐dependent enhancement in the in vitro enhancement assays. Thus, antibodies targeting immature virus can predict disease severity and could be used in early forecast of disease outcome using an enzyme‐linked immunoassay assay system which is less laborious and cheaper than plaque assay system for correlates of protection and could help optimize medical care and resources.

Dengue is a tropical disease caused by the Dengue virus (DENV), a positive-sense, single stranded RNA virus of the family Flaviviridae, which is transmitted by Aedes mosquitoes. The occurrence of dengue has grown dramatically around the globe in recent decades, and it is rapidly becoming a global burden. Furthermore, all four DENV serotypes cocirculate and create a problematic hyperendemic situation. Characteristic symptoms range from being asymptomatic, dengue fever to life-threatening complications such as hemorrhagic fever and shock. Apart from the inherent virulence of the virus strain, a dysregulated host immune response makes the condition worse. Currently, there is no highly recommended vaccine or therapeutic agent against dengue. With the advent of virus strains resistant to antiviral agents, there is a constant need for new therapies to be developed. Since time immemorial, human civilization has utilized plants in traditional medicine to treat various diseases, including infectious viral diseases. With the advancement in molecular biology, cell biology techniques, and bioinformatics, recent studies have tried to provide scientific evidence and determine the mechanism of anti-dengue activity of various plant extracts and plant-derived agents. The current Review consolidates the studies on the last 20 years of in vitro and in vivo experiments on the ethnomedicinal plants used against the dengue virus. Several active phytoconstituents like quercetin, castanospermine, α-mangostin, schisandrin-A, hirsutin have been found to be promising to inhibition of all the four DENV serotypes. However, novel therapeutics need to be reassessed in relevant cells using high-throughput techniques. Further, in vivo dose optimization for the immunomodulatory and antiviral activity should be examined on a vast sample size. Such a Review should help take the knowledge forward, validate it, and use medicinal plants in different combinations targeting multiple stages of virus infection for more effective multipronged therapy against dengue infection.