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COVID-19 caused by the SARS-CoV-2 is a current global challenge and urgent discovery of potential drugs to combat this pandemic is a need of the hour. 3-chymotrypsin-like cysteine protease (3CLpro) enzyme is the vital molecular target against the SARS-CoV-2. Therefore, in the present study, 1528 anti-HIV1compounds were screened by sequence alignment between 3CLpro of SARS-CoV-2 and avian infectious bronchitis virus (avian coronavirus) followed by machine learning predictive model, drug-likeness screening and molecular docking, which resulted in 41 screened compounds. These 41 compounds were re-screened by deep learning model constructed considering the IC 50 values of known inhibitors which resulted in 22 hit compounds. Further, screening was done by structural activity relationship mapping which resulted in two structural clefts. Thereafter, functional group analysis was also done, where cluster 2 showed the presence of several essential functional groups having pharmacological importance. In the final stage, Cluster 2 compounds were re-docked with four different PDB structures of 3CLpro, and their depth interaction profile was analyzed followed by molecular dynamics simulation at 100 ns. Conclusively, 2 out of 1528 compounds were screened as potential hits against 3CLpro which could be further treated as an excellent drug against SARS-CoV-2.

In this study, we utilized an untargeted NMR metabolomics approach to identify the vector response in terms of metabolic profiling after temperature and insecticide exposure in comparison with the control. Clearly, temperature and insecticide exposure cause changes in the underlying metabolism, and the NMR metabolomic profile enables a direct examination of the immediate response of the vector to cope up with these changes. The present study was designed in four parts: A- Aedes aegypti were exposed to 40 °C for one-hour, DDT-4%, malathion-5%, and deltamethrin-0.05% separately and, part B-D; one-hour exposure at 35 °C and 40 °C temperatures followed by one-hour exposure to insecticide. The resultant metabolite profiles were compared with the control. In response to temperature and insecticide exposure, several metabolites and altered pathways were identified. Citrate, maltose, lipids, Nicotinate, Choline, Pyruvate and β-hydroxybutyrate were found as important components of major biological pathways such as tri-carboxylic acid cycle, branched amino acid degradation, glycolysis/gluconeogenesis, amino acid metabolism, lipid and carbohydrate metabolism, nucleotide PRPP pathway, and phospholipid metabolism. Furthermore, the results also suggest that the changes imposed by exposure to temperature and insecticides individually, are reversed with combined exposure, thus negating the impact of each other and posing a threat to the control of Aedes-borne diseases such as dengue, chikungunya, Zika and yellow fever.

Malaria has inflicted serious morbidity and mortality across the globe. The major brunt of the disease has been on African, South-East Asian and South American countries. Proportionally, malaria has attracted global research priorities and this is evident from the number of publications related to malaria from across the globe, irrespective of its endemicity. However, formal and exhaustive analyses of these ‘malaria publications’ are rarely reported. The systematic review and secondary data analyses were done to retrieve information on what has been published on malaria, where is it published, and which countries are major contributors to malaria research. The study presents malaria publications from 1945 to 2020 retrieved using three databases: Web of Science ™ , Embase ® and Scopus ® . Exported data were examined to determine the number of publications over time, their subject areas, contributions from various countries/organizations, and top publishing journals. The total number of published records on malaria ranged from 90,282 to 112,698 (due to three different databases). Based on the number of publications, USA, UK, France, and India were identified as the top four countries. Malaria Journal, American Journal of Tropical Medicine & Hygiene, and PLoS One were the most preferred journals, whereas the University of London (Institutions other than LSHTM), the National Institute of Health, the London School of Hygiene and Tropical Medicine, and the University of Oxford appeared to be the top contributing organization. A disproportional contribution to malaria research was observed with non-malaria endemic countries making the largest contribution. Databases differed in their output format and needed standardization to make the outputs comparable across databases.

Visceral leishmaniasis (VL) is a vector-borne disease caused by the digenetic protozoan parasite Leishmania donovani complex. So far there is no effective vaccine available against VL. The DDX3 DEAD-box RNA Helicase ( Hel67 ) is 67 kDa protein which is quite essential for RNA metabolism, amastigote differentiation, and infectivity in L. major and L. infantum . To investigate the role of Hel67 in the L. donovani , we created L. donovani deficient in the Hel67 . Helicase67 null mutants ( LdHel67 −/− ) were not able to differentiate as axenic amastigotes and were unable to infect the hamster. So, we have analyzed the prophylactic efficacy of the LdHel67 −/− null mutant in hamsters. The LdHel67 −/− null mutant based candidate vaccine exhibited immunogenic response and a higher degree of protection against L. donovani in comparison to the infected control group. Further, the candidate vaccine displayed antigen-specific delayed-type hypersensitivity (DTH) as well as strong antibody response and NO production which strongly correlates to long term protection of candidate vaccine against the infection. This study confirms the potential of LdHel67 −/− null mutant as a safe and protective live attenuated vaccine candidate against visceral leishmaniasis.

Malaria is still a public health challenge across many regions of the world. With significant efforts, it has become a target for elimination in near future. However, elimination requires early and accurate diagnosis and despite the fact that malaria elimination is nearing in several countries, specific and sensitive diagnosis of malaria and its causative species remains inadequate in many near-elimination settings, including India. With the advent and increasing usage of nucleic acid-based detection of infection, the diagnostic limitations of microscopy, including errors in species identification, have become more prominent. The purpose of this study was to determine the magnitude of species misidentification by microscopy in India based on previously published reports that performed microscopy and PCR to the same samples. A total of 2706 microscopy-PCR pairs were extracted from 16 different locations across 11 Indian states. Region-specific and species-wise misidentification rates were also estimated. The analyses revealed 15% misidentification rate (408/2706). Surprisingly, microscopy misidentified >98% of mixed-infections (400/405) as mono-infections (almost all as mono-infections). The study identifies Jharkhand and Madhya Pradesh as major contributors (>20%) to species misidentification by microscopy. These findings suggest that we are overestimating burden, potentially wasting elimination resources, and underestimating non-falciparum species. The study also addresses an important issue concerning analysis of misidentification and sub-microscopic infection data. It proposes an analysis approach that is expected to help in deciphering misidentification and sub-microscopic infections in a more granular manner, generating actionable data for countries targeting malaria elimination.

Despite clinical and pathological distinctions between malaria and hypertension, accumulated epidemiological and evolutionary evidence indicate the need of deeper understanding how severe malaria contributes to elevated hypertension risk. Malaria is said to exert strong selection pressure on the host genome, thus selecting certain genetic polymorphisms. Few candidate polymorphisms have also been reported in the RAS (ACE I/D and ACE2 rs2106809) that are shown to increase angiotensin II (ang II) levels in a combinatorial manner. The raised ang II has some antiplasmodial actions in addition to protecting against severe/cerebral malaria. It is hypothesized that RAS polymorphisms may have been naturally selected over time in the malaria-endemic areas in such a way that hypertension, or the risk thereof, is higher in such areas as compared to non-malaria endemic areas. The purpose of this review is to gain deeper insights into various sparse evidence linking malaria and hypertension and suggesting a way forward.

Nipah virus (NiV) is an emerging zoonotic virus that caused several serious outbreaks in the south asian region with high mortality rates ranging from 40 to 90% since 2001. NiV infection causes lethal encephalitis and respiratory disease with the symptom of endothelial cell-cell fusion. No specific and effective vaccine has yet been reported against NiV. To address the urgent need for a specific and effective vaccine against NiV infection, in the present study, we have designed two Multi-Epitope Vaccines (MEVs) composed of 33 Cytotoxic T lymphocyte (CTL) epitopes and 38 Helper T lymphocyte (HTL) epitopes. Out of those CTL and HTL combined 71 epitopes, 61 novel epitopes targeting nine different NiV proteins were not used before for vaccine design. Codon optimization for the cDNA of both the designed MEVs might ensure high expression potential in the human cell line as stable proteins. Both MEVs carry potential B cell linear epitope overlapping regions, B cell discontinuous epitopes as well as IFN-γ inducing epitopes. Additional criteria such as sequence consensus amongst CTL, HTL and B Cell epitopes was implemented for the design of final constructs constituting MEVs. Hence, the designed MEVs carry the potential to elicit cell-mediated as well as humoral immune response. Selected overlapping CTL and HTL epitopes were validated for their stable molecular interactions with HLA class I and II alleles and in case of CTL epitopes with human Transporter Associated with antigen Processing (TAP) cavity. The structure based epitope cross validation for interaction with TAP cavity was used as another criteria choosing final epitopes for NiV MEVs. Finally, human Beta-defensin 2 and Beta-defensin 3 were used as adjuvants to enhance the immune response of both the MEVs. Molecular dynamics simulation studies of MEVs-TLR3 ectodomain (Human Toll-Like Receptor 3) complex indicated the stable molecular interaction. We conclude that the MEVs designed and in silico validated here could be highly potential vaccine candidates to combat NiV infections, with great effectiveness, high specificity and large human population coverage worldwide.

Second Internal Transcribed Spacer (ITS2) ribosomal DNA (rDNA) sequence is a widely used molecular marker for species-identification or -delimitation due to observed concerted evolution which is believed to homogenize rDNA copies in an interbreeding population. However, intra-specific differences in ITS2 of Anopheles stephensi have been reported. This study reports the presence of intragenomic sequence variation in the ITS2-rDNA of An . stephensi and hypothesizes that observed intra-specific differences in this species may have resulted due to ambiguous DNA sequence-chromatogram resulting from intragenomic heterogeneity. Anopheles stephensi collected from different parts of India were sequenced for complete ITS2 and the variable region of 28S-rDNA (d1-d3 domains). Intragenomic variations were found in ITS2 region of all An . stephensi sequenced, but no such variation was observed in d1 to d3 domains of 28S-rDNA. Cloning and sequencing of ITS2 through the d3 domain of the 28S region of rDNA from representative samples from northern, central, and southern India confirmed the presence of intragenomic variation in ITS2 due to transitions at three loci and two bp indel in a di-nucleotide microsatellite locus. Multiple haplotypes were observed in ITS2 raised from such variations. Due to the absence of detectable intragenomic sequence variation in the d1 to d3 domain of 28S rDNA of An . stephensi , this region can serve as an ideal reference sequence for taxonomic and phylogenetic studies. The presence of intragenomic variation in rDNA should be carefully examined before using this as a molecular marker for species delimitation or phylogenetic analyses.

The present study uses a systematic approach to explore the phytochemical composition of medicinal plants from Uttarakhand, Western Himalaya. The phytochemical composition of medicinal plants was analyzed based on (i) the presence of different chemical groups and (ii) bioactive compounds. The Generalized Additive Model ( GAM) analysis was used to predict the occurrence of chemical groups and active compounds across different eco-climatic zones and the elevation in Uttarakhand. A total of 789 medicinal plants represented by 144 taxonomic families were screened to explore the phytochemical diversity of the medicinal plants of Uttarakhand. These medicinal plant species are signified in different life forms such as herbs (58.86%), shrubs (18.24%), trees (17.48%), ferns (2.38%), and climbers (2.13%). The probability of occurrence of the chemical groups found in tropical, sub-tropical, and warm temperate eco-climatic zones, whereas active compounds have a high Probability towards alpine, sub-alpine, and cool temperate zones. The GAM predicted that the occurrence of species with active compounds was declining significantly (p < 0.01), while total active compounds increased across elevation (1000 m). While the occurrence of species with the chemical group increased, total chemical groups were indicated to decline with increasing elevation from 1000 m (p < 0.000). The current study is overwhelmed to predict the distribution of phytochemicals in different eco-climatic zones and elevations using secondary information, which offers to discover bioactive compounds of the species occurring in the different eco-climatic habitats of the region and setting the priority of conservation concerns. However, the study encourages the various commercial sectors, such as pharmaceutical, nutraceutical, chemical, food, and cosmetics, to utilize unexplored species. In addition, the study suggests that prioritizing eco-climatic zones and elevation based on phytochemical diversity should be a factor of concern in the Himalayan region, especially under the climate change scenario.