scholarly journals Identification of vaccine and drug targets in Shigella dysenteriae sd197 using reverse vaccinology approach

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Khurshid Jalal ◽  
Tareq Abu-Izneid ◽  
Kanwal Khan ◽  
Muhammad Abbas ◽  
Ajmal Hayat ◽  
...  
Keyword(s):  
Drug Targets ◽  
Diarrheal Disease ◽  
Vaccine Candidate ◽  
Shigella Dysenteriae ◽  
Reverse Vaccinology ◽  
World Health ◽  
Vaccine Candidates ◽  
Subtractive Genomics ◽  
Health Organization ◽  
Chimeric Vaccine

AbstractShigellosis is characterized as diarrheal disease that causes a high mortality rate especially in children, elderly and immunocompromised patients. More recently, the World Health Organization advised safe vaccine designing against shigellosis due to the emergence of Shigella dysenteriae resistant strains. Therefore, the aim of this study is to identify novel drug targets as well as the design of the potential vaccine candidates and chimeric vaccine models against Shigella dysenteriae. A computational based Reverse Vaccinology along with subtractive genomics analysis is one of the robust approaches used for the prioritization of drug targets and vaccine candidates through direct screening of genome sequence assemblies. Herein, a successfully designed peptide-based novel highly antigenic chimeric vaccine candidate against Shigella dysenteriae sd197 strain is proposed. The study resulted in six epitopes from outer membrane WP_000188255.1 (Fe (3+) dicitrate transport protein FecA) that ultimately leads to the construction of twelve vaccine models. Moreover, V9 construct was found to be highly immunogenic, non-toxic, non-allergenic, highly antigenic, and most stable in terms of molecular docking and simulation studies against six HLAs and TLRS/MD complex. So far, this protein and multiepitope have never been characterized as vaccine targets against Shigella dysenteriae. The current study proposed that V9 could be a significant vaccine candidate against shigellosis and to ascertain that further experiments may be applied by the scientific community focused on shigellosis.

scholarly journals SCREENING OF PUTATIVE THERAPEUTIC CANDIDATES IN SUPERBUG (STAPHYLOCOCCUS AUREUS): A SYSTEMATIC IN SILICO APPROACH

2016 ◽  
pp. 283 ◽  
Author(s):  
Kiranmayi Patnala ◽  
Kunal Zaveri
Keyword(s):  
Staphylococcus Aureus ◽  
In Silico ◽  
Structure Prediction ◽  
Drug Targets ◽  
Vaccine Candidate ◽  
Antigenic Property ◽  
Optimal Treatment ◽  
Reverse Vaccinology ◽  
Antibiotic Resistant ◽  
Vaccine Candidates

<p>ABSTRACT<br />Objective: Staphylococcus aureus, a superbug and antibiotic resistant pathogen, is one of the most infection causing organism, ranging from skin<br />allergies to severe lethal conditions. The prolonged use of different antibiotics and lack of optimal treatment over the antibiotic resistant species, led<br />to the identification of new, better and promising therapeutic candidates. <br />Methods: A systematic in silico filtration process was employed, which includes subtractive channels and reverse vaccinology techniques. <br />Results: Here, we report 12 possible drug targets and two vaccine candidates based on essentiality, non-human homolog, virulent and localization,<br />commonly in all the strains. Further characterization studies such as pathway analysis, chokepoint and structure prediction revealed, two proteins<br />as the best drug targets one being novel and the other druggable. Only one protein has shown the characteristic feature of vaccine candidate, having<br />antigenic property and an IgG binding domain. <br />Conclusion: Two best drug targets were commonly identified in all the strains of S. aureus namely UDP-N-acetylmuramoyl-L-alanyl-D-glutamate--L-lysine<br />ligase (MurE) and cell division protein FtsA, whereas the best common vaccine candidate includes Peptidoglycan binding protein. The therapeutic candidates<br />reported in the present study might facilitate screening of new and better antimicrobial compounds, for an optimal treatment of S. aureus infections.<br />Keywords: Staphylococcus aureus, Drug target, Vaccine candidates, Subtractive proteomics, Reverse vaccinology.</p>

An Insight into the Current Perspective and Potential Drug Targets for Visceral Leishmaniasis (VL)

2020 ◽  
Vol 21 (11) ◽  
pp. 1105-1129
Author(s):  
Rani Mansuri ◽  
Jagbir Singh ◽  
Anupama Diwan
Keyword(s):  
Drug Targets ◽  
Redox Homeostasis ◽  
World Health ◽  
Metabolism Pathway ◽  
Thiol Metabolism ◽  
Development Of Resistance ◽  
Current Perspective ◽  
Fatal Form ◽  
Novel Target ◽  
Health Organization

Leishmaniasis is one of the six entities on the list of most important diseases of the World Health Organization/Tropical Disease Research (WHO/TDR). After Malaria, it is one of the most prevalent and lethal parasitic diseases. VL is the fatal form of this disease, especially if left untreated. The drugs that are currently available for the treatment of VL are expensive, toxic, or no longer effective, especially in endemic regions. Currently, no vaccine has been developed to immunize humans against VL. The major problems with the current drugs are the development of resistance and their adverse effects. Therefore, there is a strong urge to research and design drugs that have better efficacies and low toxicities as compared to current chemotherapeutic drugs. Leishmania has various enzymes involved in its metabolic pathways, which are unique to either the same genus or trypanosomatids, making them a very suitable, attractive and novel target sites for drug development. One of the significant pathways unique to trypanosomatids is the thiol metabolism pathway, which is involved in the maintenance of redox homeostasis as well as protection of the parasite in the macrophage from oxidative stress-induced damage. In this review the several pathways, their essential enzymes as well as the proposed changes in the parasites due to drug resistance have been discussed to help to understand the most suitable drug target. The thiol metabolism pathway is discussed in detail, providing evidence of this pathway being the most favorable choice for drug targeting in VL.

Outbreak of coronavirus disease 2019 (COVID-19) and its manifestation

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Bikash Debnath ◽  
Waikhom Somraj Singh ◽  
Kuntal Manna
Keyword(s):  
Antiviral Drug ◽  
World Health ◽  
Family Welfare ◽  
Pregnant Mother ◽  
Vaccine Candidates ◽  
The World ◽  
Mode Of Transmission ◽  
Health Organization ◽  
Effective Drugs ◽  
Respiratory Droplets

: The coronavirus disease 2019 (COVID-19) first outbreak in Wuhan, China, and the infection is intense worldwide. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for COVID-19. The World Health Organization (WHO) confirmed total deaths had noted 4.20% globally (March 21, 2020). Between the intervals of four months (July 21, 2020), confirmed total deaths had recorded 4.17%, globally. In India, 909 confirmed cases and 19 deaths were reported by Health and Family Welfare, Government of India, March 28, 2020. Between the intervals of 123 days In India, 1638870 confirmed cases and 35684 deaths. COVID-19 can potentially spread from person to person through direct contact or respiratory droplets from coughing and sneezing. The most common symptoms are fever, dry cough, difficulty in breathing, and fatigue. A pregnant mother with COVID-19 has fewer chances to transfer this infection of her newborn babies. Children have less affected than an adult. A specific antiviral drug or vaccine has not been developed to cure the disease. Chloroquine, hydroxychloroquine, lopinavir, ritonavir, nafamostat, nitazoxanide, and remdesivir have effective drugs to treat COVID-19. Many vaccine candidates are under pre-clinical and clinical studies. In this review, we highlight the epidemiology, sign-symptoms, pathogenesis, mode of transmission, and effects of a pregnant mother with newborns, children, prevention, and drugs affective to COVID-19.

scholarly journals Two Live Attenuated Vaccines against Recent Low–and Highly Pathogenic H7N9 Influenza Viruses Are Safe and Immunogenic in Ferrets

Vaccines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 74 ◽  
Author(s):  
Larisa Rudenko ◽  
Irina Kiseleva ◽  
Elena Krutikova ◽  
Ekaterina Stepanova ◽  
Irina Isakova-Sivak ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Reverse Genetics ◽  
Vaccine Candidate ◽  
Clinical Signs ◽  
Influenza Viruses ◽  
Phase I Clinical Trial ◽  
World Health ◽  
Histological Data ◽  
Health Organization

Influenza H7N9 virus is a potentially pandemic subtype to which most people are immunologically naïve. To be better prepared for the potential occurrence of an H7N9 pandemic, in 2017 the World Health Organization recommended developing candidate vaccine viruses from two new H7N9 viruses, A/Guangdong/17SF003/2016 (A/GD) and A/Hong Kong/125/2017 (A/HK). This report describes the development of live attenuated influenza vaccine (LAIV) candidates against A/GD and A/HK viruses and study of their safety and immunogenicity in the ferret model in order to choose the most promising one for a phase I clinical trial. The A/HK-based vaccine candidate (A/17/HK) was developed by classical reassortment in eggs. The A/GD-based vaccine candidate (A/17/GD) was generated by reverse genetics. Ferrets were vaccinated with two doses of LAIV or phosphate-buffered saline. Both H7N9 LAIVs tested were safe for ferrets, as shown by absence of clinical signs, and by virological and histological data; they were immunogenic after a single vaccination. These results provide a compelling argument for further testing of these vaccines in volunteers. Since the A/HK virus represents the cluster that has caused the majority of human cases, and because the A/HK-based LAIV candidate was developed by classical reassortment, this is the preferred candidate for a phase I clinical trial.

scholarly journals Mycobacterial cell wall biosynthesis: a multifaceted antibiotic target

Parasitology ◽  
2016 ◽  
Vol 145 (2) ◽  
pp. 116-133 ◽  
Author(s):  
KATHERINE A. ABRAHAMS ◽  
GURDYAL S. BESRA
Keyword(s):  
Cell Wall ◽  
Drug Targets ◽  
Complex Structure ◽  
Supporting Cell ◽  
Chemotherapeutic Agents ◽  
World Health ◽  
Mycobacterial Cell ◽  
Clinical Drugs ◽  
Health Organization ◽  
Mycobacterial Cell Wall

SUMMARYMycobacterium tuberculosis(Mtb), the etiological agent of tuberculosis (TB), is recognized as a global health emergency as promoted by the World Health Organization. Over 1 million deathsperyear, along with the emergence of multi- and extensively-drug resistant strains ofMtb, have triggered intensive research into the pathogenicity and biochemistry of this microorganism, guiding the development of anti-TB chemotherapeutic agents. The essential mycobacterial cell wall, sharing some common features with all bacteria, represents an apparent ‘Achilles heel’ that has been targeted by TB chemotherapy since the advent of TB treatment. This complex structure composed of three distinct layers, peptidoglycan, arabinogalactan and mycolic acids, is vital in supporting cell growth, virulence and providing a barrier to antibiotics. The fundamental nature of cell wall synthesis and assembly has rendered the mycobacterial cell wall as the most widely exploited target of anti-TB drugs. This review provides an overview of the biosynthesis of the prominent cell wall components, highlighting the inhibitory mechanisms of existing clinical drugs and illustrating the potential of other unexploited enzymes as future drug targets.

scholarly journals Breast Feeding versus Formula Feeding and Diarrheal Diseases in Infants and Children- A Review

2014 ◽  
Vol 32 (1) ◽  
pp. 26-30 ◽  
Author(s):  
MUH Begum
Keyword(s):  
Breast Feeding ◽  
Exclusive Breastfeeding ◽  
Diarrheal Disease ◽  
Formula Feeding ◽  
Infants And Children ◽  
World Health ◽  
Human Breast Milk ◽  
Diarrheal Diseases ◽  
Health Organization ◽  
In Infants And Children

The World Health Organization (WHO) and the American Academy of Pediatrics (AAP) emphasize the value of breastfeeding for mothers as well as children. Both recommend exclusive breastfeeding for the first six months of life. Human breast milk is the healthiest form of milk for babies. Breastfeeding promotes health and helps to prevent diseases including diarrheal diseases. It contains all nutrients including antibodies (IgA),and lactoferrin, that potentially prevent infection and diarrhea in infants and children. Studies conducted in both developed and under developed nations have found that breast feeding is associated with significantly ( upto 64%) less diarrheal disease and the protective effect of breast feeding does not persist beyond two months after breast feeding is stopped. On the other hand, formula fed infants are found an upto 80% increased in the risk of developing diarrhea compared to breast fed infants and there is significantly more diarrheal disease in formula fed infants. Infection may be attributable to contamination of bottles, teats, milk, and food in infants who are not exclusively breastfed. Exclusive breastfeeding for the first six months of life and there after complementary feedings while breastfeeding continues for up to two years of age or beyond, enthusiastic support and involvement from clinicians, obstetricians and pediatricians, are essential in “breastfeeding vs formula feeding” issue and to reduce incidence of diarrheal diseases in infants and children. DOI: http://dx.doi.org/10.3329/jbcps.v32i1.21033 J Bangladesh Coll Phys Surg 2014; 32: 26-30

scholarly journals Surveillance of Antimicrobial Resistance in Salmonella, Shigella, andVirvio choleraein Latin America and the Caribbean: A Collaborative Project

2000 ◽  
Vol 11 (4) ◽  
pp. 181-185 ◽  
Author(s):  
David L Woodward ◽  
Frank G Rodgers
Keyword(s):  
Antimicrobial Resistance ◽  
Latin American ◽  
Diarrheal Disease ◽  
Health Care Systems ◽  
Public Health Care ◽  
World Health ◽  
Major Health Problem ◽  
Local Public Health ◽  
Health Organization ◽  
The Impact

Diarrheal disease is recognized as the most frequent cause of morbidity and mortality in children worldwide (1). Current estimates indicate that at least 3.5 million children under the age of five years die each year due to diarrhea (1). Indeed, the World Health Organization (WHO) and the Pan American Health Organization (PAHO) have identified acute gastroenteritis as a major health problem in all Latin American countries (2). Mortality associated with acute diarrhea is highest among infants younger than one year of age, and death rates average 20/1000 children born (2). The impact of lives lost, together with the high costs to local public health care systems associated with treatment of those afflicted, make prevention and control of diarrheal disease a priority health issue (2). Over the past decade, these concerns have been further reinforced by the emergence of antimicrobial resistance among the major groups of enteric pathogens causing disease.

scholarly journals Perspectives on RNA Vaccine Candidates for COVID-19

2021 ◽  
Vol 8 ◽  
Author(s):  
Pobitra Borah ◽  
Pran Kishore Deb ◽  
Nizar A. Al-Shar’i ◽  
Lina A. Dahabiyeh ◽  
Katharigatta N. Venugopala ◽  
...  
Keyword(s):  
Viral Vectors ◽  
Vaccine Development ◽  
Lessons Learned ◽  
Public Health Care ◽  
World Health ◽  
Genetic Sequencing ◽  
Vaccine Candidates ◽  
Clinical Investigations ◽  
Current Outbreak ◽  
Health Organization

With the current outbreak caused by SARS-CoV-2, vaccination is acclaimed as a public health care priority. Rapid genetic sequencing of SARS-CoV-2 has triggered the scientific community to search for effective vaccines. Collaborative approaches from research institutes and biotech companies have acknowledged the use of viral proteins as potential vaccine candidates against COVID-19. Nucleic acid (DNA or RNA) vaccines are considered the next generation vaccines as they can be rapidly designed to encode any desirable viral sequence including the highly conserved antigen sequences. RNA vaccines being less prone to host genome integration (cons of DNA vaccines) and anti-vector immunity (a compromising factor of viral vectors) offer great potential as front-runners for universal COVID-19 vaccine. The proof of concept for RNA-based vaccines has already been proven in humans, and the prospects for commercialization are very encouraging as well. With the emergence of COVID-19, mRNA-1273, an mRNA vaccine developed by Moderna, Inc. was the first to enter human trials, with the first volunteer receiving the dose within 10 weeks after SARS-CoV-2 genetic sequencing. The recent interest in mRNA vaccines has been fueled by the state of the art technologies that enhance mRNA stability and improve vaccine delivery. Interestingly, as per the “Draft landscape of COVID-19 candidate vaccines” published by the World Health Organization (WHO) on December 29, 2020, seven potential RNA based COVID-19 vaccines are in different stages of clinical trials; of them, two candidates already received emergency use authorization, and another 22 potential candidates are undergoing pre-clinical investigations. This review will shed light on the rationality of RNA as a platform for vaccine development against COVID-19, highlighting the possible pros and cons, lessons learned from the past, and the future prospects.

scholarly journals Nano COVID-19 Vaccines: the firsts RNA lipid nanoparticle vaccines being approved from history - Review

2020 ◽  
Vol 9 (12) ◽  
pp. e20191211123
Author(s):  
Thyago José Arruda Pacheco ◽  
Victor Carlos Mello da Silva ◽  
Danielle Galdino de Souza
Keyword(s):  
World Health ◽  
World Population ◽  
Phase 3 ◽  
Vaccine Candidates ◽  
The Third ◽  
The World ◽  
Proven Efficacy ◽  
Pros And Cons ◽  
Health Organization ◽  
Collaborative Efforts

A new coronavirus, identified in Wuhan, China, has spread globally, infecting millions of people and causing significant morbidity and mortality. The pandemic state, declared by the World Health Organization on March 11, 2020, transformed the world and made people adapt to social distance to control the spread of the virus. The race against time in search of therapeutic solutions has become essential, and nanotechnology may be able to make vaccines available in record time to stimulate the immunization of individuals. Since the beginning of 2020, scientists and companies are rapidly advancing to make vaccine candidates available at a different rate compared to other pandemics that have existed. This review briefly presents the pros and cons of the third generation vaccines, Moderna / NIAID and Pfizer - BioNTech, which are in phase 3 tests, based on lipid RNA nanoparticles. Great collaborative efforts are being invested so that soon the world population will receive doses of vaccines with proven efficacy and enable increased survival, since the pandemic has already caused many irreversible losses.

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