In silico study to predict promiscuous peptides for immunodiagnosis of cystic echinococcosis.

Background: Cystic echinococcosis (CE), caused by Echinococcus granulosus, is a major zoonotic disease that causes significant human morbidity and mortality. This cosmopolitan disease is difficult to diagnose, treat, and control. So far, crude extracts of hydatid cyst fluid containing antigen B or antigen 5 have been used as the primary antigenic source for its immunodiagnosis. The main issue is that it reacts with sera from people infected with other helminths. There is currently no standard, specific, or sensitive test for disease diagnosis, and no human vaccine has been reported. Aims and Objectives: Considering the need for efficient immunization and/or immunodiagnosis, six E. granulosus antigens, antigen 5, antigen B, heat shock proteins such as Hsp-8 and Hsp-90, phosphoenolpyruvate carboxykinase, and tetraspanin-1, were chosen. Materials and Methods: Using various in silico tools, T cell and B cell epitopes (promiscuous peptides) were predicted by targeting antigen 5, antigen B, heat shock proteins such as Hsp-8 and Hsp-90, phosphoenolpyruvate carboxykinase, and tetraspanin-1. Results: There are twelve promiscuous peptides with overlapping human leukocyte antigen (HLA) class-I, class-II, and conformational B cell epitopes. Such immunodominant peptides could be useful as subunit vaccines. Furthermore, six peptides specific for E. granulosus were also discovered, which may prove to be important markers in the diagnosis of CE, potentially preventing misdiagnosis and mismanagement. Conclusion: These epitopes may be the most important vaccine targets in E. granulosus because they have the most promiscuous peptides and B cell epitopes, as well as the highest affinity for different alleles, as determined by docking scores. However, additional research using in vitro and in vivo models is undertaken.

A ricin-based peptide BRIP from Hordeum vulgare inhibits Mpro of SARS-CoV-2.

COVID-19 pandemic caused by SARS-CoV-2 led to the research aiming to find the inhibitors of this virus. Towards this world problem, an attempt was made to identify SARS-CoV-2 main protease (Mpro) inhibitory peptides from ricin domains. The ricin-based peptide from barley (BRIP) was able to inhibit Mpro in vitro with an IC50 of 0.52 nM. Its low and no cytotoxicity upto 50 µM suggested its therapeutic potential against SARS-CoV-2. The most favorable binding site on Mpro was identified by molecular docking and steered molecular dynamics (MD) simulations. The Mpro-BRIP interactions were further investigated by evaluating the trajectories for microsecond timescale MD simulations. The structural parameters of Mpro-BRIP complex were stable, and the presence of oppositely charged surfaces on the binding interface of BRIP and Mpro complex further contributed to the overall stability of the protein-peptide complex. Among the components of thermodynamic binding free energy, Van der Waals and electrostatic contributions were most favorable for complex formation. Our findings provide novel insight into the area of inhibitor development against COVID-19.

COVID-19: the impetus for change-sustaining healthcare team communication in times of social distancing.

The COVID-19 pandemic has challenged existing healthcare systems and has made prevention of healthcare personnel exposure a high priority. Essential healthcare services, including multi-disciplinary team (MDT) meetings that make medical decisions, are expected to continue uninterrupted in this time of social distancing. There are a multitude of virtual platforms available to enable remote MDT meetings, and the pandemic has accelerated their arrival into daily healthcare practice. While we deal with a pandemic crisis, we have comprehensively reviewed and reported on the popular platforms and services available for this purpose. While each platform has its own unique features and drawbacks, it is essential to liaise with information technology departments and data governance teams to understand the optimal platforms for use within each healthcare setting. Level of evidence: Not ratable.

Immuno-informatics approach to design a multi-epitope vaccine to combat cytomegalovirus infection.

Human cytomegalovirus (HCMV) poses a serious public health problem causing morbidity and mortality in transplant recipients, immunocompromised patients, and congenitally infected newborns. Considering the recent reports of emergence of Ganciclovir drug resistance, vaccine development is the need of an hour. In the present study, a multi-epitope vaccine was constructed targeting the major hotspot- the pentavalent complex of glycoproteins (H/L/UL128-UL130-UL131) of HCMV, and other important target proteins- gB and pp65. The vaccine designed was composed of series of epitopes belonging to CD4, CD8 and B cells. As an immunobooster, the CpG motifs was linked to the vaccine which severed as an adjuvant. The affinity, stability and flexibility of the vaccine construct with the immune receptor- Toll like receptor -9 (TLR-9) was investigated by molecular docking and molecular dynamics simulations. The in-silico immune simulations of the vaccine sequence were also carried out to determine its ability to stimulate different immune components. Further, an in-silico cloning of the vaccine construct was performed to analyze the feasibility of its expression and translation efficiency in pET-28a (+) vector. The overall results obtained indicated the vaccine to be immunogenic, non-allergic, had high population coverage, high affinity and stability with the immune receptor, had efficient expression in host E. coli and was effective in stimulating different immune cell types like T helper, T cytotoxic, B cells, dendritic cells, macrophages and interleukins. The proposed vaccine construct is expected to be highly efficacious and needs to be carried forward by the vaccinologists to test its efficacy in lab settings.

Designing a multi-epitope based vaccine to combat Kaposi Sarcoma utilizing immunoinformatics approach.

Kaposi's sarcoma-associated herpesvirus (KSHV) responsible for causing Kaposi sarcoma (KS), an opportunistic angioproliferative neoplasm is emerging rapidly. Despite this there is no permanent cure for this disease. The present study was aimed to design a multi-epitope based vaccine targeting the major glycoproteins of KSHV which plays an important role in the virus entry. After the application of rigorous immunoinformatics analysis and several immune filters, the multi-epitope vaccine was constructed, consisting of CD4, CD8 and IFN-γ inducing epitopes. Several physiochemical characteristics, allergenicity and antigenicity of the multi-epitope vaccine were analyzed in order to ensure its safety and immunogenicity. Further, the binding affinity and stability of the vaccine with Toll like receptor -9 (TLR-9) was analyzed by molecular docking and dynamics simulation studies. In addition, an in silico cloning was performed to ensure the expression and translation efficiency of the vaccine, utilizing pET-28a (+) vector. Such T-cell-based immunotherapies which leverage this mechanism could prove their potential against cancer. Further, the authors propose to test the present findings in the lab settings to ensure the safety, immunogenicity and efficacy of the presented vaccine which may help in controlling KSHV infection.

Plaster Burn: Challenge to Plastic Surgeon.

BACKGROUND: The thermal burn is accidental and also is the hidden and worst complication of medical plaster application. This study evaluated clinical and aetiological profile and severity of plaster burns. METHODS: In Department of Burns, Plastic and Reconstructive Surgery from 1st August 2014 to 31st December 2015, six patients with plaster burn were assessed for total body surface area and depth of burn. The wounds were cultured and dressed with moist dressings daily till the surgical procedure and satisfactory healing. RESULTS: The youngest patient was 10 and oldest 65 years (mean age: 40.20±6.67 years, 4 males and two females with ratio of 2:1). Three patients sustained plaster burn injury accidentally at home and 3 developed burn after medical application of plaster. The hands burns were observed commonly in accidental plaster burns, while ankle was often involved in iatrogenic plaster burns. The iatrogenic burns were mostly deep in thickness varying 2nd to 4th degree, while accidental burns were often 2nd degree. Superficial 2nd degree burns were managed conservatively, and deep 2nd degree burns were skin grafted. Fourth degree burn was managed with reverse sural flap alone and another with vacuum-assisted closure followed by reverse sural flap and skin grafting. CONCLUSION: Plaster burn is still a challenge to plastic surgeon and it is advised for applying casts to utilize all available means to limit the amount of casting material provided. It can be accomplished without compromising the cast strength to minimize the risk of thermal injury when applying plaster or composite casts.