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The Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in outbreak of global pandemic, fatal pneumonia in human referred as Coronavirus Disease-2019 (Covid-19). Ayurveda, the age old practice of treating human ailments in India, can be considered against SARS-CoV-2. Attempt was made to provide preliminary evidences for interaction of 35 phytochemicals from two plants (Phyllanthus amarus and Andrographis paniculata used in Ayurveda) with SARS-CoV-2 proteins (open & closed state S protein, 3CLpro, PLpro and RdRp) through in silico docking analysis. The nucleotide analogue remdesivir, being used in treatment of SARS-CoV-2, was used as a positive control. The results revealed that 18 phytochemicals from P. amarus and 14 phytochemicals from A. paniculata shown binding energy affinity/dock score < − 6.0 kcal/mol, which is considered as minimum threshold for any compound to be used for drug development. Phytochemicals used for docking studies in the current study from P. amarus and A. paniculata showed binding affinity up to − 9.10 kcal/mol and − 10.60 kcal/mol, respectively. There was no significant difference in the binding affinities of these compounds with closed and open state S protein. Further, flavonoids (astragalin, kaempferol, quercetin, quercetin-3-O-glucoside and quercetin) and tannins (corilagin, furosin and geraniin) present in P. amarus have shown more binding affinity (up to − 10.60 kcal/mol) than remdesivir (up to − 9.50 kcal/mol). The pharmacokinetic predictions suggest that compounds from the two plants species studied in the current study are found to be non-carcinogenic, water soluble and biologically safe. The phytochemicals present in the extracts of P. amarus and A. paniculata might have synergistic effect with action on multiple target sites of SARS-CoV-2. The information generated here might serve as preliminary evidence for anti SARS-CoV-2 activity of phytochemicals present from P. amarus and A. paniculata and the potential of Ayurveda medicine in combating the virus. [ABSTRACT FROM AUTHOR]

Corona virus pandemic outbreak also known as COVID-19 has created an imbalance in this world. Scientists have adopted the use of natural or alternative medicines which are consumed mostly as dietary supplements to boost the immune system as herbal remedies. India is famous for traditional medicinal formulations which includes 'Trikadu'-a combination of three acrids, namely Zingiber officinale, Piper nigrum and Piper longum which have antioxidant properties that boost our immune system hence acting as a strong preventive measure. In this study, AutoDock 4.0 was used to study interaction between the phytocompounds of Trikadu with RNA-dependent polymerase protein and enveloped protein of the SARS-CoV-2 virus. Analysis of the results showed that coumarin, coumaperine and bisdemethoxycurcumin showed strong bonding interactions with both the proteins. We can conclude that Trikadu has the potential molecules; hence, it can be incorporated in the diet to boost the immune system as a preventive measure against the virus., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The present study evaluates the vulnerability of the lake system (Deepor Beel) due to the combined exposure of toxic metals, major ions and mineral dissociation. The hydro-chemistry of the Deepor Beel lake reveals the dominance of carbonate weathering with strong evidences of ion-exchange reaction occurring throughout the monsoon season of 2014 and 2015. Through an integrated application of multivariate analysis, the occurrence of albite weathering was confirmed, although as an isolated incidence only, along-with substantial evidence of waste water intrusion from fertilizer industries. The moderate cation exchange capacity (CEC) of the soil, indicates the presence of illite, chlorite and kaolinite which provides a strong buffering action in terms of phosphorous and nutrient retention. However, occurrences of chemical waste in the form of bleaching powder (Ca(OCl) 2 ) are causing acidification of lake soil, which will trigger the release of phosphorous and may enhance the eutrophication level in near future. Through the simulations of Biotic Ligand (BL) model on ceriodaphnia dubia, it is being revealed, that the free availability of Ca 2+ in the lake water, provides a higher adsorptive competition for labile metal species especially for Cu and Zn. Additionally, the risk among children from drinking lake water, has increased by three to seven times in a duration of just one year. The present study is a pioneering work, which has evaluated the vulnerability of Deepor Beel lake by adopting a sequential assessment strategy of lake internal as well as external ecology. Our proposed methodology can be a used as a scientific basis for future assessment of the lake health., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Reticulocyte binding protein-like homologs (RHs) are currently being evaluated as anti-erythrocytic stage vaccine targets against Plasmodium falciparum malaria. Present study explores the possible evolutionary drivers shaping the genetic organization of Pfrhs in Indian parasite population. It simultaneously evaluates a putative gain-of-function variant of PfRH5, a keystone member of PfRH family., Methods: Receptor binding regions of Pfrh1, Pfrh2a/b, Pfrh4 and whole Pfrh5 were amplified using blood samples of P. falciparum malaria patients from Chhattisgarh and West Bengal and sequenced. Assembled sequences were analysed using MEGA7 and DnaSPv6. Binding affinities of recombinant PfRH5 proteins with basigin (BSG) were compared using in silico (CHARMM and AUTODOCK) and in vitro (Circular dichroism, fluorescence spectroscopy and isothermal titration calorimetry) methods., Results: Pfrh1 (0.5), Pfrh2a/b (0.875), Pfrh4 (0.667) and Pfrh5 (0.778) sequence changes corresponded to low frequency (< 0.05) variants which resulted in an overall negative Tajima's D. Since mismatch distribution of none of the Pfrh loci corroborated with the model of demographic expansion, a possible role of natural selection formulating Pfrh sequence diversity was investigated. Among the 5 members, Pfrh5 displayed very high dN/dS (5.7) ratio. Nevertheless, the model of selective sweep due to presence of any advantageous substitutions could not be invoked as polymorphic nonsynonymous sites (17/18) for Pfrh5 exceeded significantly over the divergent (62/86) ones (p = 0.0436). The majority of extant PfRH5 sequences (52/83) differed from the reference Pf3D7 allele by a single amino acid mismatch (C203Y). This non-conservative alteration was predicted to lower the total interaction energy of that PfRH5 variant with BSG, compared to PfRH5 3D7 . Biophysical evidences validated the proposition that PfRH5 variant formed a more stable complex with BSG. Thermodynamic association constant for interaction of BSG with PfRH5 variant was also found to be higher (Ka variant  = 3.63E6 ± 2.02E6 M -1 and Ka 3D7  = 1.31E6 ± 1.21E6 M -1 )., Conclusions: Together, the study indicates that the genetic architecture of Pfrhs is principally shaped by purifying selection. The most abundant and ubiquitous PfRH5 variant harbouring 203Y, exhibits a greater affinity for BSG compared to PfRH5 3D7 possessing 203C allele. The study underscores the importance of selecting the functional allele that best represents circulating strains in natural parasite populations as vaccine targets.

The G-quadruplex (GQ) motifs are considered as potential drug-target sites for several human pathogenic viruses such as Zika, Hepatitis, Ebola, and Human Herpesviruses. The recent outbreaks of Nipah virus (NiV) in India, the highly fatal emerging zoonotic virus is a potential threat to global health security as no anti-viral drug or vaccine in currently available. Therefore, here in the present study, we sought to assess the ability of the putative G-quadruplex forming sequences in the NiV genome to form G-quadruplex structures and act as targets for anti-viral compounds. Bioinformatics analysis underpinned by various biophysical and biochemical techniques (such as NMR, CD, EMSA, DMS footprinting assay) confirmed the presence of two highly conserved G-quadruplex forming sequences (HGQs) in the G and L genes of NiV. These genes encode the cell attachment glycoprotein and RNA-dependent RNA polymerase, respectively and are essential for the virus entry and replication within the host cell. It remains possible that stabilization of these HGQs by the known G-quadruplex binding ligands like TMPyP4 and Braco-19 represents a promising strategy to inhibit the expression of the HGQ harboring genes and thereby stop the viral entry and replication inside the host cell. Accordingly, we report for the first time, that HGQs in Nipah virus genome are targets for G-quadruplex specific ligands; therefore, could serve as potential targets for anti-viral therapy.

Galectin-3, a β-galactoside-binding lectin, has been implicated in vast repertoire of inflammatory and immunomodulatory processes including skin diseases. However, galectin-3 has not been comprehensively studied in infectious diseases. This study emphasizes on fascinating aspects of galectin-3 expression in dermal infection by studying post-kala-azar dermal leishmaniasis (PKDL), an intracellular infection caused by Leishmania donovani. Indian PKDL is a well-recognized parasitic dermatosis, with a high risk of anthroponotic transmission of L. donovani in causing leishmaniasis. This study aims to investigate the levels of galectin-3 and galectin-3-binding site expression in circulation of different forms of Indian patients with PKDL. Thirty-seven confirmed untreated PKDL patients, comprising 20 polymorphic and 17 macular PKDL manifestations, were evaluated for the levels of sera galectin-3 with respect to 28 age- and sex-matched healthy controls from endemic areas. Result shows a significant increment (P < 0.001) in circulatory galectin-3 levels in PKDL variants as compared to healthy controls. In addition, there were heightened levels of galectin-3 and galectin-3-binding sites on cellular infiltrates on lesional sites. Furthermore, there was a positive correlation between frequencies of mononuclear cells and galectin-3 during microcirculation in lesions. Data were well corroborated with positive correlation of IL-10 and IFN-γ with sera galectin-3 levels. Moreover, flow cytometry demonstrated the enhanced expression levels of the galectin-3-binding site in circulation in patients with PKDL as compared to healthy controls. Taken together, elevated levels of galectin-3 reflect its involvement in PKDL pathogenesis.

Background The clinical application of rapidly developing new molecular tests in breast cancer is debatable and often not affordable for most of the patients from developing countries. We assessed the adoption of molecular testing and their utility in breast cancer patients in the setting of a developing Nation. Methods We analysed the results of next-generation sequencing (NGS) based BRCA1 and 2 and multi-gene testing, immunohistochemistry based (IHC) based mismatch repair genes (MMR), Programmed cell death ligand 1(PDL1) and Androgen receptor (AR) testing done in breast cancer patients diagnosed from 2015 to 2018. Results There was an overall increase in the number of molecular tests offered to breast cancer patients in subsequent years. 141 patients opted for BRCA testing out of which 56 (40%) were triple negative (TNBC). 27(19%) out of 141 patients were BRCA mutated and 8(6%) had variants of unknown significance (VUS). Among 15 metastatic breast cancer patients tested for mutations on Multi-gene NGS, 3 had Her2neu amplification. Out of 8 TNBC cases, 5 had TP53 mutation, 1 had exon 14 skipping mutation of MET gene and 1 showed EGFR amplification. None of the five and six breast cancer patients with TNBC tested for MMR and PD-L1 were MMR deficient or positive respectively. Of the 7 TNBC patients tested, 4 were found to have Androgen receptor expression. Conclusions There is a significant rise in the use of modern molecular techniques in developing nations like India. However, Country Specific guidelines guided by International guidelines and awareness in patients with specific counseling on advantages and disadvantages of these tests may help in the usage of these techniques by most needy patients, breast cancer in particular. Legal entity responsible for the study Rajiv Gandhi Cancer Institute and Research Centre, New Delhi. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

The human MN blood group antigens are isoforms of glycophorin A (GPA) encoded by the gene, GYPA, and are the most abundant erythrocyte sialoglycoproteins. The distribution of MN antigens has been widely studied in human populations yet the evolutionary and/or demographic factors affecting population variation remain elusive. While the primary function of GPA is yet to be discovered, it serves as the major binding site for the 175-kD erythrocyte-binding antigen (EB-175) of the malarial parasite, Plasmodium falciparum, a major selective pressure in recent human history. More specifically, exon two of GYPA encodes the receptor-binding ligand to which P. falciparum binds. Accordingly, there has been keen interest in understanding what impact, if any, natural selection has had on the distribution of variation in GYPA and exon two in particular. To this end, we resequenced GYPA in individuals sampled from both P. falciparum endemic (sub-Saharan Africa and South India) and non-endemic (Europe and East Asia) regions of the world. Observed patterns of variation suggest that GYPA has been subject to balancing selection in populations living in malaria endemic areas and in Europeans, but no such evidence was found in samples from East Asia, Oceania, and the Americas. These results are consistent with malaria acting as a selective pressure on GYPA, but also suggest that another selective force has resulted in a similar pattern of variation in Europeans. Accordingly, GYPA has perhaps a more complex evolutionary history, wherein on a global scale, spatially varying selective pressures have governed its natural history.

Killer cell immunoglobulin-like receptors (KIRs) regulate the activation of natural killer cells (NKs). Qualitative and quantitative differences in the type and the number of KIRs expressed on NK cells affect its activation which would influence the outcome of the disease. In this study, 114 hospitalized cases of dengue [82 dengue fever (DF) and 32 dengue haemorrhagic fever (DHF) cases] and 104 healthy controls (HC) without no known history of hospitalization for dengue-like illness were investigated for their KIR gene profile to find out the association of KIR genes with dengue disease severity. KIR gene profile was investigated using duplex sequence-specific priming polymerase chain reaction-based typing system. The results revealed a higher frequency of KIR3DL1 gene [P = 0.0225; odds ratio (OR) 4.1 95% confidence interval (CI) 1.1-14.8] and lower frequency of KIR3DS1/3DS1 genotype [P = 0.0225; OR 0.24 95% CI (0.068-0.88)] in DF cases compared to HC. Immunoglobulin-like receptor gene frequencies were not different between DHF and DF or HC. The results suggest that KIR3DL1/KIR3DS1 locus might be associated with the risk of developing DF., (© 2015 John Wiley & Sons Ltd.)

Introduction: NK cell function is regulated by cell surface inhibitory and activating receptors including the C-type lectin receptors and Killer Immunoglobulin-like receptors (KIR). The effect of immune modulating cytokines produced by NK cells in the pathogenesis of end stage renal disease (ESRD) remained intriguing. In this regard the present study assesses the combinatorial association of KIR gene content and KIR receptor-HLA ligand in the North Indian ESRD patients., Material and Methods: KIR gene polymorphism as a susceptible marker in ESRD among 512 patients and 512 ethnically matched controls was analyzed. PCR-SSP based genotyping for KIR gene content and HLA-A, B, C typing was carried out., Results: Significant difference in frequencies of KIR2DS1-HLA-C2 (p≤0.0001, OR=1.98, CI=1.50-2.61), KIR2DS2-HLAC1 (p≤0.0001, OR=1.87, CI=1.42-2.46), KIR3DS1-HLA-Bw4 (p=0.0038, OR=1.46, CI=1.13-1.88) combinations for ESRD was found. In the combinatorial analysis Bw4(+)/3DL1(-)/3DS1(+) (p≤0.0001, OR=4.90, CI=2.75-8.71) and C1(+)/2DL2(-)/2DL3(-)/2DS2(+)/2DS3(+) (p=0.0037, OR=2.50, CI=1.35-4.63) showed risk association. KIR3DS1 was observed to be susceptible for all four primary kidney disease groups., Conclusion: NK cell de-regulation due to HLA ligand binding KIR receptors may be involved in the patho-physiology of ESRD. Upon analyzing the data in this context it was found that C2/C2 donor might improve the clinical outcome of patients having C2 ligands., (Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.)

Introduction: Killer immunoglobulin-like receptor (KIR)-ligand mismatches lead to natural killer cell alloreactivity after hematopoietic stem cell transplantation (HSCT). However, their clinical impact on HSCT outcomes is controversial due to complexity of KIR haplotypes, genotypes, and phenotypes as well as their diversity among patient populations. The present study investigated the role of KIR-ligand interactions in human leukocyte antigen (HLA)-matched sibling transplants., Methods: The recipient cohort, which included patients diagnosed with aplastic anemia, acute leukemia, and myelodysplastic syndrome, received granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood stem cells. HLA typing was performed using polymerase chain reaction - sequence specific oligo probes (PCR-SSO). The KIR genotype of the donors and the ligands C1 (Asparagine 80), C2 (Lysine 80), and Bw4 recipient typings were performed using polymerase chain reaction - sequence specific primers (PCR-SSP). We assessed acute and chronic graft-versus-host disease (GVHD), relapse, and overall survival., Results: While 84.5% of donors carried a Bx KIR, 15.5% carried the AA haplotype. The effect of a recipient's lack of ligands among 88.5% of cases was associated with 39% of subjects developing GvHD. Lack of C1 may lead to manifestations of acute GvHD and lack of C2 to manifestation of chronic GvHD. The presence of both C1 and C2 seemed to be protective against both forms of GvHD. The role of two Bw4 alleles, threonine (T) or isoleucine (I) at position 80, was evaluated. 73% of recipients who carried Bw4 80(I) versus 27% with the Bw4 80(T) allele. The presence of Bw4-80(T) allele appeared to reduce the risk of GvHD, indicating its stronger inhibitory effect than its 80(I) counterpart., Conclusion: KIR-ligand interactions influenced HSCT outcomes., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Toll-like receptor 2 (TLR2) is a member of TLR family. It recognizes a wide range of bacteria and their products, and is involved in inducing innate immune responses. In this article, we reported inductive expression of TLR2 and myeloid differentiation primary response gene 88 (MyD88)-dependent signaling in the Indian major carp, mrigal (Cirrhinus mrigala) which is highly commercially important fish species in the Indian subcontinent. Ontogeny analysis of TLR2, MyD88 and TRAF6 (TNF receptor associated factor 6) genes by quantitative real-time PCR (qRT-PCR) revealed constitutive expression of these genes in all embryonic developmental stages, indicating their involvement in embryonic innate immune defense system in fish. Tissue specific expression analysis of these genes by qRT-PCR showed their wide distribution in various organs and tissues. Highest expression of TLR2 was in gill, MyD88 in liver and TRAF6 was in kidney. Inductive expression of TLR2, MyD88 and TRAF6 genes were observed following peptidoglycan (PGN)-treatment, and Streptococcus uberis and Aeromonas hydrophila infections. Expression of interleukin (IL)-8 and TNF-α in various organs were significantly enhanced by PGN-treatment and bacterial infections, and were closely associated with TLR2 induction. These findings together highlighted the contribution of TLR2 in augmenting innate immunity in fish, and indicated it's important role in immune surveillance of various organs during pathogenic invasion. This study will enrich the information in understanding the innate immune mechanism in fish, and will be helpful in developing preventive measures against infectious diseases in fish.

Tay Sachs disease (TSD) is a neurodegenerative disorder due to β-hexosaminidase A deficiency caused by mutations in the HEXA gene. The mutations leading to Tay Sachs disease in India are yet unknown. We aimed to determine mutations leading to TSD in India by complete sequencing of the HEXA gene. The clinical inclusion criteria included neuroregression, seizures, exaggerated startle reflex, macrocephaly, cherry red spot on fundus examination and spasticity. Neuroimaging criteria included thalamic hyperdensities on CT scan/T1W images of MRI of the brain. Biochemical criteria included deficiency of hexosaminidase A (less than 2% of total hexosaminidase activity for infantile patients). Total leukocyte hexosaminidase activity was assayed by 4-methylumbelliferyl-N-acetyl-β-D-glucosamine lysis and hexosaminidase A activity was assayed by heat inactivation method and 4-methylumbelliferyl-N-acetyl-β-D-glucosamine-6-sulphate lysis method. The exons and exon-intron boundaries of the HEXA gene were bidirectionally sequenced using an automated sequencer. Mutations were confirmed in parents and looked up in public databases. In silico analysis for mutations was carried out using SIFT, Polyphen2, MutationT@ster and Accelrys Discovery Studio softwares. Fifteen families were included in the study. We identified six novel missense mutations, c.340 G>A (p.E114K), c.964 G>A (p.D322N), c.964 G>T (p.D322Y), c.1178C>G (p.R393P) and c.1385A>T (p.E462V), c.1432 G>A (p.G478R) and two previously reported mutations. c.1277&#95;1278insTATC and c.508C>T (p.R170W). The mutation p.E462V was found in six unrelated families from Gujarat indicating a founder effect. A previously known splice site mutation c.805+1 G>C and another intronic mutation c.672+30 T>G of unknown significance were also identified. Mutations could not be identified in one family. We conclude that TSD patients from Gujarat should be screened for the common mutation p.E462V.