Influenza A (H1N1) Virus Outbreak in the Districts of Chhattisgarh: A Cross-Sectional Study.

Background The H1N1 flu is a subtype of the influenza A virus, also known as the swine flu. An entirely new strain of the H1N1 virus started sickening people in the 2009-2010 flu season. It was a novel influenza virus combination that can infect humans, pigs, and birds. It was frequently referred to as the "swine flu." The virus may be able to spread for a little while longer in children and individuals with compromised immune systems. Objective The objective is to investigate the outbreaks of H1N1 among young adults in the Bastar District of Chhattisgarh. Methods Collection of the blood samples of 342 individuals between December 2015 and November 2017 was done. Thirty-one cases of Influenza A (H1N1) PDM09 virus infection were identified and confirmed. The molecular relationship between viruses is identified by the real-time polymerase chain reaction (RT-PCR) method. Result The majority of samples (n=13) were sourced from Raipur Medical College, followed by contributions from Durg District Hospital (n=5), Raigarh Medical College (n=4), Rajnandgaon District Hospital (n=3), Jagdalpur Medical College (n=2), Bilaspur Medical College (n=2), and smaller contributions from Dhamtari District Hospital and Gariyabandh Primary Health Care. Among these, 31 samples tested positive for Influenza A (H1N1) PDM 2009 virus, with a slightly higher prevalence among 19 female patients. Age-wise distribution revealed higher proportions of positive cases in the age groups of 0-10 years, 31-40 years, and 21-30 years. In the molecular analysis, 154 samples showed no target amplification, while 125 samples exhibited amplification of only Influenza A without subtype (H1) amplification. Remarkably, 31 patients who tested positive for Influenza A (H1N1) died from the virus; most of the deaths were in children under five and middle-aged adults. Conclusion The detection of Influenza A (H1N1) PDM 2009 virus, especially among females, indicates its persistent circulation. Positive cases were prevalent among younger and middle-aged individuals. Molecular analysis showed subtype variations, with significant fatalities observed in children under five and middle-aged adults, emphasizing the severity of the virus across different age groups. It is advised that in order to keep Indian influenza surveillance up to date and robust, more epidemiological data should be gathered, along with information on risk factors like immunization status, hospitalization, and mortality rates should be estimated, and influenza case subtyping should be improved.

Japanese Encephalitis Outbreak in Young Adults of Bastar District in Chhattisgarh: A Short Observational Study.

Background Instant infections in children due to acute encephalitis syndrome (AES) were reported in a tribal district of Bastar in Chattisgarh, India, between August 2018 and August 2019. Objective The study was conducted to explore the possibility of a viral cause indicating an outbreak. Methods Clinical surveys and serological investigation tests were conducted to identify the viral etiology. The Bastar area in Chhattisgarh reported factors such as paddy fields near homes, a high pig-to-cattle ratio, a significant presence of Culex vishnui mosquitoes, low socioeconomic status, and a lack of health awareness among the tribal people. Result This study, conducted at the Late Baliram Kashyap Memorial Government Medical College in Jagdalpur, Bastar, Chhattisgarh, India, analyzed 128 samples from fever cases out of 213 patients visiting the Japanese encephalitis virus (JEV) testing center. Among these samples, 71 cases exhibited AES, and subsequent JEV IgM ELISA testing identified 18 cases as JEV-positive, signifying recent JEV infections. Notably, the overwhelming majority (94.44%) of JEV-positive patients were under 16 years old, highlighting the heightened vulnerability of children to JEV illness in the Bastar region. Although male patients accounted for 61.11% of the JEV-positive cases compared to 38.88% of female patients, statistical analysis revealed that this gender disparity was not statistically significant (p-value = 0.18). Conclusion The study emphasizes the significance of identifying the etiology and delivering evidence-based care to patients with AES. Improved diagnosis and management of AES may result from a greater comprehension of the advantages and disadvantages associated with the application and administration of common laboratory and diagnostic algorithms.

Synthesis and inhibition studies towards the discovery of benzodiazepines as potential antimalarial compounds.

The target-based discovery of therapeutics against apicoplast, an all-important organelle is an overriding perspective. MEP pathway, an accredited drug target provides an insight into the importance of apicoplast in the survival of the parasite. In this study, we present the rational design strategy employing sustainable catalysis for the synthesis of benzodiazepine (BDZ) conformers followed by their biological evaluation as prospective inhibitors against the potential target of the IPP pathway, 1-deoxy-D-xylulose-5-phosphatereductoisomerase (DXR). The study reported the inhibitory profile of 8c and 6d against the quintessential step of the only drug target in the erythrocytic stages of parasite development. The potential compounds were identified to represent a novel class of inhibitors that serve as the lead molecules to impede the pathway and further affect the survival of the parasite.

Relict plastidic metabolic process as a potential therapeutic target.

The alignment of the evolutionary history of parasites with that of plants provides a different panorama in the drug development process. The housing of different metabolic processes, essential for parasite survival, adds to the indispensability of the apicoplast. The different pathways responsible for fueling the apicoplast and parasite offer a myriad of proteins responsible for the apicoplast function. The studies emphasizing the target-based approaches might help in the discovery of antimalarials. The different putative drug targets and their roles are highlighted. In addition, the origin of the apicoplast and metabolic processes are reviewed and the different drugs acting upon the enzymes of the apicoplast are discussed.

Signaling Strategies of Malaria Parasite for Its Survival, Proliferation, and Infection during Erythrocytic Stage.

Irrespective of various efforts, malaria persist the most debilitating effect in terms of morbidity and mortality. Moreover, the existing drugs are also vulnerable to the emergence of drug resistance. To explore the potential targets for designing the most effective antimalarial therapies, it is required to focus on the facts of biochemical mechanism underlying the process of parasite survival and disease pathogenesis. This review is intended to bring out the existing knowledge about the functions and components of the major signaling pathways such as kinase signaling, calcium signaling, and cyclic nucleotide-based signaling, serving the various aspects of the parasitic asexual stage and highlighted the Toll-like receptors, glycosylphosphatidylinositol-mediated signaling, and molecular events in cytoadhesion, which elicit the host immune response. This discussion will facilitate a look over essential components for parasite survival and disease progression to be implemented in discovery of novel antimalarial drugs and vaccines.

Plasmodium falciparum apicoplast and its transcriptional regulation through calcium signaling.

Malaria has been present since ancient time and remains a major global health problem in developing countries. Plasmodium falciparum belongs to the phylum Apicomplexan, largely contain disease-causing parasites and characterized by the presence of apicoplast. It is a very essential organelle of P. falciparum responsible for the synthesis of key molecules required for the growth of the parasite. Indispensable nature of apicoplast makes it a potential drug target. Calcium signaling is important in the establishment of malaria parasite inside the host. It has been involved in invasion and egress of merozoites during the asexual life cycle of the parasite. Calcium signaling also regulates apicoplast metabolism. Therefore, in this review, we will focus on the role of apicoplast in malaria biology and its metabolic regulation through Ca++ signaling.

In-silico studies on DegP protein of Plasmodium falciparum in search of anti-malarials.

Despite encouraging progress over the past decade, malaria caused by the Plasmodium parasite continues to pose an enormous disease burden and is one of the major global health problems. The extreme challenge in malaria management is the resistance of parasites to traditional monochemotherapies like chloroquine and sulfadoxine-pyrimethamine. No vaccine is yet in sight, and the foregoing effective drugs are also losing ground against the disease due to the resistivity of parasites. New antimalarials with novel mechanisms of action are needed to circumvent existing or emerging drug resistance. DegP protein, secretory in nature has been shown to be involved in regulation of thermo-oxidative stress generated during asexual life cycle of Plasmodium, probably required for survival of parasite in host. Considering the significance of protein, in this study, we have generated a three-dimensional structure of PfDegP followed by validation of the modeled structure using several tools like RAMPAGE, ERRAT, and others. We also performed an in-silico screening of small molecule database against PfDegP using Glide. Furthermore, molecular dynamics simulation of protein and protein-ligand complex was carried out using GROMACS. This study substantiated potential drug-like molecules and provides the scope for development of novel antimalarial drugs.

Recent Updates on DTD (D-Tyr-tRNA(Tyr) Deacylase): An Enzyme Essential for Fidelity and Quality of Protein Synthesis.

During protein synthesis, there are several checkpoints in the cell to ensure that the information encoded within genetic material is decoded correctly. Charging of tRNA with its cognate amino acid is one of the important steps in protein synthesis and is carried out by aminoacyl-tRNA synthetase (aaRS) with great accuracy. However, due to presence of D-amino acids in the cell, sometimes aaRS charges tRNA with D-amino acids resulting in the hampering of protein translational process, which is lethal to the cell. Every species has some mechanism in order to prevent the formation of D-amino acid-tRNA complex, for instance DTD (D-Tyr-tRNA deacylase) is an enzyme responsible for the cleavage of ester bond formed between D-amino acid and tRNA leading to error free translation process. In this review, structure, function, and enzymatic mechanism of DTD are discussed. The role of DTD as a drug target is also considered.

Plasmodium falciparum Secretome in Erythrocyte and Beyond.

Plasmodium falciparum is the causative agent of deadly malaria disease. It is an intracellular eukaryote and completes its multi-stage life cycle spanning the two hosts viz, mosquito and human. In order to habituate within host environment, parasite conform several strategies to evade host immune responses such as surface antigen polymorphism or modulation of host immune system and it is mediated by secretion of proteins from parasite to the host erythrocyte and beyond, collectively known as, malaria secretome. In this review, we will discuss about the deployment of parasitic secretory protein in mechanism implicated for immune evasion, protein trafficking, providing virulence, changing permeability and cyto-adherence of infected erythrocyte. We will be covering the possibilities of developing malaria secretome as a drug/vaccine target. This gathered information will be worthwhile in depicting a well-organized picture for host-pathogen interplay during the malaria infection and may also provide some clues for the development of novel anti-malarial therapies.

Structure-based binding between protein farnesyl transferase and PRL-PTP of malaria parasite: an interaction study of prenylation process in Plasmodium.

Protein prenylation is a post-translational modification critical for many cellular processes such as DNA replication, signaling, and trafficking. It is mediated by protein farnesyltransferase by recognizing 'CAAX' motif on protein substrate. Plasmodium falciparum also possesses many such proteins with 'CAAX' motif, involved in various pathways of the parasite. The interaction studies of PfPFT with its substrate were carried out using synthetic peptides but not with full protein. Therefore, in this study, we have modeled both PfPFT and its substrate protein tyrosine phosphatase (PfPRL-PTP) followed by interaction studies using protein-protein docking and molecular dynamics simulation. Our findings provided a clear picture of interactions at atomic level between prenyltransferase and its protein substrate. We are assured that this piece of information can be extended to many other proteins of parasite containing 'CAAX' motif and that it may also lead to the development of anti-malarials based on the inhibition of prenylation-dependent pathways of parasite..

Molecular modeling, in silico screening and molecular dynamics of PfPRL-PTP of P. falciparum for identification of potential anti-malarials.

Millions of deaths occur every year due to malaria. Growing resistance against existing drugs for treatment of malaria has exaggerated the problem further. There is an intense demand of identifying drug targets in malaria parasite. PfPRL-PTP protein is PRL group of phosphatase, and one of the interesting drug targets being involved in three important pathways of malaria parasite (secretion, phosphorylation, and prenylation). Therefore, in this study, we have modeled three-dimensional structure of PfPRL-PTP followed by validation of 3D structure using RAMPAGE, verify3D, and other structure validation tools. We could identify 12 potential inhibitory compounds using in silico screening of NCI library against PfPRL-PTP with Glide. The molecular dynamics simulation was also performed using GROMACS on PfPRL-PTP model alone and PfPRL-PTP-inhibitor complex. This study of identifying potential drug-like molecules would add up to the process of drug discovery against malaria parasite.