Tracing down the Updates on Dengue Virus-Molecular Biology, Antivirals, and Vaccine Strategies.

BACKGROUND: Nearly half of the world is at risk of developing dengue infection. Dengue virus is the causative agent behind this public healthcare concern. Millions of dengue cases are reported every year, leading to thousands of deaths. The scientific community is working to develop effective therapeutic strategies in the form of vaccines and antiviral drugs against dengue. METHODS: In this review, a methodological approach has been used to gather data from the past five years to include the latest developments against the dengue virus. RESULTS: Different therapeutics and antiviral targets against the dengue virus are at different stages of development, but none have been approved by the FDA. Moreover, various vaccination strategies have also been discussed, including attenuated virus vaccines, recombinant subunit vaccines, viral vector vaccines, DNA vaccines, nanotechnology, and plant-based vaccines, which are used to develop effective vaccines for the dengue virus. Many dengue vaccines pass the initial phases of evaluation, but only two vaccines have been approved for public use. DENGVAXIA is the only FDA-approved vaccine against all four stereotypes of the dengue virus, but it is licensed for use only in individuals 6-16 years of age with laboratory-confirmed previous dengue infection and living in endemic countries. Takeda is the second vaccine approved for use in the European Union, the United Kingdom, Brazil, Argentina, Indonesia, and Thailand. It produced sustained antibody responses against all four serotypes of dengue virus, regardless of previous exposure and dosing schedule. Other dengue vaccine candidates at different stages of development are TV-003/005, TDENV PIV, V180, and some DNA vaccines. CONCLUSION: There is a need to put more effort into developing effective vaccines and therapeutics for dengue, as already approved vaccines and therapeutics have limitations. DENGVAXIA is approved for use in children and teenagers who are 6-16 years of age and have confirmed dengue infection, while Takeda is approved for use in certain countries, and it has withdrawn its application for FDA approval.

Monkeypox Virus: A Comprehensive Overview of Viral Pathology, Immune Response, and Antiviral Strategies.

BACKGROUND: The years 2022-2023 witnessed a monkeypox virus (mpox) outbreak in some countries worldwide, where it exists in an endemic form. However, the number of infectious cases is continuously on the rise, and there has been an unexpected, drastic increase in cases that result from sustained transmission in non-endemic regions of the world. Under this scenario, it is pertinent for the world to be aware of healthcare threats to mpox infection. This review aimed to compile advanced data regarding the different aspects of mpox disease. METHODS: A comprehensive strategy for the compilation of recent data was adopted to add data regarding mpox, biology, viral pathology, immune response, and brief details on the antiviral strategies under trial; the search was limited to 2016-2023. The aim is to make the scientific community aware of diverse aspects of mpox. RESULTS: Consequently, detailed insights have been drawn with regard to the nature, epidemiology, etiology, and biological nature of mpox. Additionally, its host interaction and viral infectious cycle and immune interventions have been briefly elaborated. This comprehensively drawn literature review delivers brief insights into the biological nature, immune responses, and clinical developments in the form of therapeutics against mpox. This study will help scientists understand the biological nature and responses in hosts, which will further help clinicians with therapeutic handling, diagnosis, and treatment options. CONCLUSIONS: This study will provide updated information on mpox's pathology, immune responses, and antiviral strategies. Moreover, it will also help the public to become educated on the healthcare-associated threat and take timely mitigation measures against expected mpox outbreaks in the future.

Recent Developments in Mpox Prevention and Treatment Options.

Human mpox is an emerging epidemic in the world. The monkey pox virus (MPXV) belongs to the same family of zoonotic Orthopoxviridae as that of the smallpox virus and exhibits similar clinical symptomology. Information regarding its diagnostics, disease epidemiology, surveillance, preventive methods, and treatment strategies are being collated with time. The purpose of this review is to trace the recent events in the scientific platform that have defined new preventive and treatment strategies against mpox. A methodological approach has been used to gather data from the latest literature to comprehensively overview the emerging treatment options. The results portion will cover details regarding the prevention of mpox. It will also shed light on a brief description of contemporary vaccines and antiviral agents that have been evaluated for their treatment potential since the emergence of the mpox threat. These treatment options are setting the pace for controlling the widespread monkeypox infection. However, the limitations attached to these treatment strategies need to be tackled quickly to increase their efficacy so that they can be deployed on a large scale for the prevention of this epidemic becoming another pandemic in this decade.

Insights into the Novel Therapeutics and Vaccines against Herpes Simplex Virus.

Herpes simplex virus (HSV) is a great concern of the global health community due to its linked infection of inconspicuous nature and resultant serious medical consequences. Seropositive patients may develop ocular disease or genital herpes as characteristic infectious outcomes. Moreover, the infectious nature of HSV is so complex that the available therapeutic options have been modified in certain ways to cure it. However, no permanent and highly effective cure has been discovered. This review generates insights into the available prophylactic and therapeutic interventions against HSV. A methodological research approach is used for study design and data complication. Only the latest data from publications are acquired to shed light on updated therapeutic approaches. These studies indicate that the current antiviral therapeutics can suppress the symptoms and control viral transmission up to a certain level, but cannot eradicate the natural HSV infection and latency outcomes. Most trials that have entered the clinical phase are made part of this review to understand what is new within the field. Some vaccination approaches are also discussed. Moreover, some novel therapeutic options that are currently in research annals are given due consideration for future development. The data can enable the scientific community to direct their efforts to fill the gaps that remain unfilled in terms of therapies for HSV. The need is to integrate scientific efforts to produce a proper cure against HSV to control the virus spread, resistance, and mutation in future disease management.

Comparison Of Efficacy Of High Dose Dexamethasone With Conventional Prednisolone In The Treatment Of Newly Diagnosed Adult Patients Of Immunthrombocytopenic Purpura.

BACKGROUND: Immune thrombocytopenic purpura with multimodal incidence having peaks in each age groups is a chronic clinical syndrome in adults, with disease more predominant in females in adults. The aim of the study was to compare the efficacy (response rate) of high dose dexamethasone with conventional prednisolone in the treatment of newly diagnosed adult patients of Immune thrombocytopenic purpura. It was a prospective quasi-experimental study, conducted at the Department of Medicine of a tertiary care hospital from Jan to Dec 2019. METHODS: The sample population comprised of 130 cases of newly diagnosed ITP patients, having platelet count <30,000/ul with or without bleeding symptoms who received either dexamethasone (40 mg/day for 04 days) or prednisolone (0.5-1 mg/kg PSL for 01 week). Treatment response was measured at day 7. RESULTS: Out of 130 patients 65 patients were treated with dexamethasone and 65 patients with prednisolone .83.08% (n=54) cases in Group-A and 33.85% (n=22) in Group-B had response while remaining 16.92% (n=11) in Group-A and 66.15% (n=43) in Group-B had no response. The p value was calculated as 0.000 which shows a significant difference. CONCLUSIONS: We concluded that high dose of dexamethasone shows a significantly higher response when compared with conventional prednisolone in the treatment of newly diagnosed adult patients of Immune thrombocytopenia purpura.

Immunoinformatics-Based Proteome Mining to Develop a Next-Generation Vaccine Design against Borrelia burgdorferi: The Cause of Lyme Borreliosis.

The tick-borne bacterium, Borrelia burgdorferi has been implicated in Lyme disease-a deadly infection, formerly confined to North America, but currently widespread across Europe and Asia. Despite the severity of this disease, there is still no human Lyme disease vaccine available. A reliable immunoinformatic approach is urgently needed for designing a therapeutic vaccine against this Gram-negative pathogen. Through this research, we explored the immunodominant proteins of B. burgdorferi and developed a novel and reliable vaccine design with great immunological predictability as well as low contamination and autoimmunity risks. Our initial analysis involved proteome-wide analysis to filter out proteins on the basis of their redundancy, homology to humans, virulence, immunogenicity, and size. Following the selection of proteins, immunoinformatic tools were employed to identify MHC class I & II epitopes and B-cell epitopes, which were subsequently subjected to a rigorous screening procedure. In the final formulation, ten common MHC-I and II epitopes were used together with a suitable adjuvant. We predicted that the final chimeric multi-epitope vaccine could invoke B-cell responses and IFN-gamma-mediated immunity as well as being stable and non-allergenic. The dynamics simulations predicted the stable folding of the designed molecule, after which the molecular docking predicted the stability of the interaction between the potential antigenic epitopes and human immune receptors. Our studies have shown that the designed next-generation vaccine stimulates desirable immune responses, thus potentially providing a viable way to prevent Lyme disease. Nevertheless, further experimental studies in a wet lab are needed in order to validate the results.

An in silico study to unveil potential drugs and vaccine chimera for HBV capsid assembly protein: combined molecular docking and dynamics simulation approach.

Humans are a major reservoir of the hepatitis B virus (HBV), therefore promising treatment and control vaccination strategies are needed to eradicate the virus. Though promising drugs and vaccines are available against HBV, still efforts are required to enrich the therapy options. Herein, the HBV assembly protein was explored to identify novel targets for future use against HBV. Computer-aided drug designing and immune-informatics techniques were employed for the identification of putative inhibitors and vaccine ensemble against HBV using capsid assembly protein. The identified drug molecule binds with high affinity to the active pocket of the protein, and several epitopes are scanned in the protein sequence. The drug molecule, besides being a good putative inhibitor, has acceptable drug-like properties. A multi-epitope vaccine is also constructed to overcome the limitations of weakly immunogenic epitopes. In contrast to the MHC II level, the set of predicted epitopes has been recognized to interact with significant numbers of HLA alleles of MHC I. Selected epitopes are extremely virulent, antigenic, nontoxic, nonallergic, have suitable affinity to bind with the prevailing DRB*0101 allele, and also spectacle 86% mediocre population coverage. A multi-epitope peptide-based vaccine chimera having 73 amino acids was designed. It emerged as substantially immunogenic, thermally stable, robust in producing cellular as well as humoral immune responses, and had competent physicochemical properties to analyze in vitro and in vivo studies. The capsid assembly protein is a in more stable nature in the presence of the drug molecule compared to the TLR3 receptor in the vaccine presence. These particulars were confirmed by exposing the docked molecules to absolute and relative binding free energy approaches of MMGBSA/PBSA. The purpose to investigate the interactions between the vaccine and a representative TLR3 immune receptor can reveal the intermolecular affinity and possible presentation mechanism of the vaccine by TLR3 to the host immune system. It was revealed that the vaccine is showing a very good affinity of binding for the TLR3 and forming a network of hydrophobic and hydrophilic interactions. Overall, the findings of this study are promising and might be useful for further experimental validations.

Computational Evaluation of Abrogation of HBx-Bcl-xL Complex with High-Affinity Carbon Nanotubes (Fullerene) to Halt the Hepatitis B Virus Replication.

Hepatitis B virus (HBV) is the world's most prevalent chronic viral infection. More than 350 million individuals are chronic carriers of the virus, with an estimated 2 billion infected persons. For instance, the role of HBx protein in attachment and infection is very obvious and consequently deemed as an important druggable target. Targeting the interface and discovering novel drugs greatly advanced the field of therapeutics development. Therefore, in the current study, HBx to Bcl-xL is abrogated on high-affinity carbon nanotubes using computational structural biology tools. Our analysis revealed that among the total 62 carbon fullerenes, only 13 compounds exhibited inhibitory activity against HBx, which was further confirmed through IFD-based rescoring. Structural dynamics investigation revealed stable binding, compactness, and hydrogen bonds reprogramming. Moreover, the binding free energy calculation results revealed that the top hits1-4 possess the total binding energy of -54.36 kcal/mol (hit1), -50.81 kcal/mol (hit2), -47.09 kcal/mol (hit3), and -45.59 kcal/mol for hit4. In addition, the predicted KD values and bioactivity scores further validated the inhibitory potential of these top hits. The identified compounds need further in vitro and in vivo validation to aid the treatment process of HBV.

Familial clustering of hepatitis C virus in a Pakistani population.

Pakistan has the second-highest burden of hepatitis C patients in the world. A total of 683 individuals, who visited the Liver Clinic during the study period, were screened for the presence of hepatitis C virus (HCV) infection. A total of 534 individuals who showed positive HCV infection were grouped into the case group and 149 individuals with HCV negative status were grouped into the control group. A detailed questionnaire was used to collect demographic, clinical, HCV risk factor, and familial clustering data. HCV familial clustering was found in 30.1% in the case group compared with 17.4% in the control group. We also found 17% of patients had spouses who were also infected with HCV compared to 4% spouse infection in the control group. Only 3.7% of patients had HCV positive mothers. These results were further expanded by regression analysis that showed that family history and sexual history are independent risk factors for transmission of hepatitis C infection and mother's history has no significance as a risk factor for transmission. The major risk factor for getting HCV infection are dental procedures, unsafe injections, surgery, and blood transfusions. There is a strong need to increase awareness about HCV transmission routes among positive patients to reduce the chances of HCV familial clustering.