An Ancient Harappan Genome Lacks Ancestry from Steppe Pastoralists or Iranian Farmers.

We report an ancient genome from the Indus Valley Civilization (IVC). The individual we sequenced fits as a mixture of people related to ancient Iranians (the largest component) and Southeast Asian hunter-gatherers, a unique profile that matches ancient DNA from 11 genetic outliers from sites in Iran and Turkmenistan in cultural communication with the IVC. These individuals had little if any Steppe pastoralist-derived ancestry, showing that it was not ubiquitous in northwest South Asia during the IVC as it is today. The Iranian-related ancestry in the IVC derives from a lineage leading to early Iranian farmers, herders, and hunter-gatherers before their ancestors separated, contradicting the hypothesis that the shared ancestry between early Iranians and South Asians reflects a large-scale spread of western Iranian farmers east. Instead, sampled ancient genomes from the Iranian plateau and IVC descend from different groups of hunter-gatherers who began farming without being connected by substantial movement of people.

Recent efforts in the development of glycoconjugate vaccine and available treatment for tuberculosis.

Tuberculosis (TB) continues to pose a grave threat to global health, despite relentless eradication efforts. In 1882, Robert Koch discovered that Mycobacterium tuberculosis (Mtb) is the bacterium responsible for causing tuberculosis. It is a fact that tuberculosis has claimed the lives of more than one billion people in the last few decades. It is imperative that we must take immediate and effective action to increase resources for TB research and treatment. Effective TB treatments demand an extensive investment of both time and finances, often requiring 6-9 months of rigorous antibiotic therapy. The most efficient way to control tuberculosis is by receiving a childhood Bacillus Calmette-Guérin (BCG) vaccination. Despite years of research on vaccine development, we still do not have any new approved vaccine for tuberculosis, except BCG, which is partially effective in young children. This review discusses briefly the available treatment for tuberculosis and remarkable advancements in glycoconjugate-based TB vaccine developments in recent years (2013-2024) and offers valuable direction for future research priorities.

Recent Efforts in Identification of Privileged Scaffolds as Antiviral Agents.

Viral infections are the most important health concern nowadays to mankind, which is unexpectedly increasing the health complications and fatality rate worldwide. The recent viral infection outbreak developed a pressing need for small molecules that can be quickly deployed for the control/treatment of re-emerging or new emerging viral infections. Numerous viruses, including the human immunodeficiency virus (HIV), hepatitis, influenza, SARS-CoV-1, SARS-CoV-2, and others, are still challenging due to emerging resistance to known drugs. Therefore, there is always a need to search for new antiviral small molecules that can combat viral infection with new modes of action. This review highlighted recent progress in developing new antiviral molecules based on natural product-inspired scaffolds. Herein, the structure-activity relationship of the FDA-approved drugs along with the molecular docking studies of selected compounds have been discussed against several target proteins. The findings of new small molecules as neuraminidase inhibitors, other than known drug scaffolds, Anti-HIV and SARS-CoV are incorporated in this review paper.

Hesperetin-loaded polymeric nanofibers: assessment of bioavailability and neuroprotective effect.

OBJECTIVE: The purpose of the study is to assess the bioavailability and neuroprotective effect of hesperetin (Hesp)-loaded nanofibers. METHODS: Electrospinning was used to create and characterize polyvinyl pyrrolidone-based Hesp-loaded nanofibers. To evaluate the produced nanofibers, preclinical studies were conducted. The study involved five groups of Wistar rats, and the treatments were administered as follows. Group 1 (control) was given regular saline for 14 d. On the 14th day, Group 2 was given scopolamine. Group 3 was given donepezil for 14 d and then scopolamine on the 14th. Group 4 was given Hesp for 14 d and then scopolamine on the 14th. Group 5 was given Hesp-loaded nanofibers for 14 d, followed by scopolamine on the 14th. On the 14th day, rats' memory was tested using Cook's pole climbing apparatus and the Morris water maze (MWM). On the 15th day, rats from each group were slaughtered, brain tissues were separated, and biochemical and histological analyses were performed. In addition, in vitro dissolution experiments and pharmacokinetic studies were carried out. RESULTS: When compared to the control group, scopolamine-treated rats had considerably longer escape latency times, as well as increased acetylcholinesterase (AChE) activity, lipid peroxidation, degeneration, and inflammation in the hippocampus. These parameters were greatly recovered by donepezil and Hesp-loaded nanofibers that had been pretreated. Because of the greatly improved bioavailability of Hesp, the Hesp-loaded nanofibers significantly protected rats from scopolamine-induced amnesia. CONCLUSIONS: Hesp-loaded nanofibers have an excellent neuroprotective effect against scopolamine-induced amnesia due to enhanced bioavailability.

13C15N: glucagon-based novel isotope dilution mass spectrometry method for measurement of glucagon metabolism in humans.

BACKGROUND: Glucagon serves as an important regulatory hormone for regulating blood glucose concentration with tight feedback control exerted by insulin and glucose. There are critical gaps in our understanding of glucagon kinetics, pancreatic α cell function and intra-islet feedback network that are disrupted in type 1 diabetes. This is important for translational research applications of evolving dual-hormone (insulin + glucagon) closed-loop artificial pancreas algorithms and their usage in type 1 diabetes. Thus, it is important to accurately measure glucagon kinetics in vivo and to develop robust models of glucose-insulin-glucagon interplay that could inform next generation of artificial pancreas algorithms. METHODS: Here, we describe the administration of novel 13C15N heavy isotope-containing glucagon tracers-FF glucagon [(Phe 6 13C9,15N; Phe 22 13C9,15N)] and FFLA glucagon [(Phe 6 13C9,15N; Phe 22 13C9,15N; Leu 14 13C6,15N; Ala 19 13C3)] followed by anti-glucagon antibody-based enrichment and LC-MS/MS based-targeted assays using high-resolution mass spectrometry to determine levels of infused glucagon in plasma samples. The optimized assay results were applied for measurement of glucagon turnover in subjects with and without type 1 diabetes infused with isotopically labeled glucagon tracers. RESULTS: The limit of quantitation was found to be 1.56 pg/ml using stable isotope-labeled glucagon as an internal standard. Intra and inter-assay variability was < 6% and < 16%, respectively, for FF glucagon while it was < 5% and < 23%, respectively, for FFLA glucagon. Further, we carried out a novel isotope dilution technique using glucagon tracers for studying glucagon kinetics in type 1 diabetes. CONCLUSIONS: The methods described in this study for simultaneous detection and quantitation of glucagon tracers have clinical utility for investigating glucagon kinetics in vivo in humans.

Inhibition of 11ß-Hydroxysteroid dehydrogenase-1 with AZD4017 in patients with nonalcoholic steatohepatitis or nonalcoholic fatty liver disease: A randomized, double-blind, placebo-controlled, phase II study.

AIM: To evaluate whether short-term treatment with a selective 11ß-Hydroxysteroid dehydrogenase-1 (11ß-HSD1) inhibitor, AZD4017, would block hepatic cortisol production and thereby decrease hepatic fat in patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), with or without type 2 diabetes (T2D). MATERIALS AND METHODS: This was a randomized, double-blind, placebo-controlled, phase 2 study conducted at two sites. Key inclusion criteria were the presence of NAFLD or NASH on magnetic resonance imaging (MRI) or recent biopsy positive for NASH. Enrolled patients were randomly assigned (1:1) to AZD4017 or placebo for 12 weeks. Primary outcomes were between-group differences in mean change from baseline to week 12 in liver fat fraction (LFF) and conversion of 13 C cortisone to 13 C cortisol in the liver. RESULTS: A total of 93 patients were randomized; 85 patients completed treatment. The mean (standard deviation [SD]) change in LFF was -0.667 (5.246) and 0.139 (4.323) in the AZD4017 and placebo groups (P = 0.441). For patients with NASH and T2D, the mean (SD) change in LFF was significantly improved in the AZD4017 versus the placebo group (-1.087 [5.374] vs. 1.675 [3.318]; P = 0.033). Conversion of 13 C cortisone to 13 C cortisol was blocked in all patients in the AZD4017 group. There were no significant between-group differences (AZD4017 vs. placebo) in changes in fibrosis, weight, levels of liver enzymes or lipids, or insulin sensitivity. CONCLUSION: Although the study did not meet one of the primary outcomes, AZD4017 blocked the conversion of 13 C cortisone to 13 C cortisol in the liver in all patients who received the drug. In patients with NASH and T2D, AZD4017 improved liver steatosis versus placebo.

Curcumin loaded mesoporous silica nanoparticles: assessment of bioavailability and cardioprotective effect.

Rhizomes of the plant Curcuma longa has been traditionally used in medicine and culinary practices in India. It possesses various pharmacological effect, namely, antioxidant, hepatoprotective, anti-inflammatory, anti-thrombosis, and anti-apoptotic. The study was undertaken to assess the effect of curcumin and curcumin loaded mesoporous silica nanoparticles (MSNs) against doxorubicin (DOX)-induced myocardial toxicity in rats. Furthermore, the study also included the bioavailability estimation of curcumin delivered alone and delivered via mesoporous technology. Cardiotoxicity was produced by cumulative administration of DOX (2.5 mg/kg for two weeks). Curcumin and curcumin loaded mesoporous nanoparticles (MSNs) each 200 mg/kg, po was administered as pretreatment for two weeks and then for two alternate weeks with DOX. The repeated administration of DOX induced cardiomyopathy associated with an antioxidant deficit and increased level of cardiotoxic biomarkers. Pretreatment with curcumin (alone and via MSNs) significantly protected myocardium from the toxic effects of DOX by significantly decreased the elevated level of malondialdehyde and increased the reduced level of reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) in cardiac tissue. MSNs based delivery was found superior compared to curcumin delivered alone. Moreover, the results of bioavailability assessment in rats clearly indicated higher Cmax and AUC values in rats when curcumin was administered via MSNs indicating superior bioavailability. The bioavailability of curcumin loaded MSNs, biochemical and histopathology reports support the good cardioprotective effect of curcumin which could be attributed to its increased bioavaibility lead to good antioxidant and anti-inflammatory activity.

Preparedness for malaria elimination in the wake of climate change in the State of Uttarakhand (India).

BACKGROUND & OBJECTIVES: Climate change is an emerging issue particularly in the context of vector-borne diseases. A study was undertaken in Nainital and Almora districts of Uttarakhand to provide evidences of changing climatic conditions, abundance of vectors, and knocking of malaria in hilly areas. MATERIAL AND METHODS: Longitudinal data on temperature and relative humidity were procured from Tussar Silk Centre, Bhimtal, India as well as generated using HOBO device. Monthly density of malaria vectors, their positivity for sporozoite proteins of malaria parasite and fever surveys were conducted as per the standard procedures from 2010 to 2013. Epidemiological data were procured from the State Programme Officer of Uttarakhand state. RESULTS: It was found that the temperature has increased since 1990 resulting in extension in windows of malaria transmission, temporal distribution as well as man hour density of Anopheles culicifacies and An. fluviatilis in hilly districts of Uttarakhand state. Both the vectors were found in high density up to a maximum man hour density of 110 (An. culicifacies) and 69 (An. fluviatilis) as compared to 32 and 33, respectively during 1998. The field collected vector species were also found positive for sporozoite proteins of malaria parasites in the month of October and November. Evidence of occurrence of malaria cases was also found in areas hitherto free from malaria. INTERPRETATION & CONCLUSION: The findings reveal that Himalayan region needs attention to strengthen surveillance for malaria to identify emerging new foci of malaria transmission in view of climate change. Health education to communities about preventive measures to contain breeding of vectors and seeking timely treatment should be imparted so as to achieve the goal of malaria elimination in category-1 in the first instance.

Synthetic, Structural, and Anticancer Activity Evaluation Studies on Novel Pyrazolylnucleosides.

The synthesis of novel pyrazolylnucleosides 3a-e, 4a-e, 5a-e, and 6a-e are described. The structures of the regioisomers were elucidated by using extensive NMR studies. The pyrazolylnucleosides 5a-e and 6a-e were screened for anticancer activities on sixty human tumor cell lines. The compound 6e showed good activity against 39 cancer cell lines. In particular, it showed significant inhibition against the lung cancer cell line Hop-92 (GI50 9.3 µM) and breast cancer cell line HS 578T (GI50 3.0 µM).

Intricacies of using temperature of different niches for assessing impact on malaria transmission.

BACKGROUND & OBJECTIVES: The influence of temperature on the life cycle of mosquitoes as well as on development of malaria parasite in mosquitoes is well studied. Most of the studies use outdoor temperature for understanding the transmission dynamics and providing projections of malaria. As the mosquitoes breed in water and rest usually indoors, it is logical to relate the transmission dynamics with temperature of micro-niche. The present study was, therefore, undertaken to understand the influence of different formats of temperature of different micro-niches on transmission of malaria for providing more realistic projections. METHODS: The study was conducted in one village each of Assam and Uttarakhand s0 tates of India. Temperatures recorded from outdoor (air) as well as indoor habitats (resting place of mosquito) were averaged into daily, fortnightly and monthly and were used for determination of transmission windows (TWs) for Plasmodium vivax (Pv) and P. falciparum (Pf) based on minimum temperature threshold required for transmission. RESULTS: The daily temperature was found more useful for calculation of sporogony than fortnightly and monthly temperatures. Monthly TWs were further refined using fortnightly temperature, keeping in view the completion of more than one life cycle of malaria vectors and sporogony of malaria parasite in a month. A linear regression equation was generated to find out the relationship between outdoor and indoor temperatures and R [2] to predict the percentage of variation in indoor temperature as a function of outdoor temperature at both localities. INTERPRETATION & CONCLUSIONS: The study revealed that the indoor temperature was more than outdoors in stable malarious area (Assam) but fluctuating in low endemic area like Uttarakhand. Transmission windows of malaria should be determined by transforming outdoor data to indoor and preferably at fortnightly interval. With daily recorded temperature, sporogonic and gonotrophic cycles can also be calculated which is otherwise not possible with monthly data. The study highlights that the projections made for malaria in view of climate change need to be seen with limitation of difference in outdoor and indoor temperatures at different locations, highlighting the need for local data generation at least at sub-district level.

Phosphonated near-infrared fluorophores for biomedical imaging of bone.

The conventional method for creating targeted contrast agents is to conjugate separate targeting and fluorophore domains. A new strategy is based on the incorporation of targeting moieties into the non-delocalized structure of pentamethine and heptamethine indocyanines. Using the known affinity of phosphonates for bone minerals in a model system, two families of bifunctional molecules that target bone without requiring a traditional bisphosphonate are synthesized. With peak fluorescence emissions at approximately 700 or 800 nm, these molecules can be used for fluorescence-assisted resection and exploration (FLARE) dual-channel imaging. Longitudinal FLARE studies in mice demonstrate that phosphonated near-infrared fluorophores remain stable in bone for over five weeks, and histological analysis confirms their incorporation into the bone matrix. Taken together, a new strategy for creating ultra-compact, targeted near-infrared fluorophores for various bioimaging applications is described.

Hyperglycemia suppresses Lactate Clearance during Exercise in Type 1 Diabetes.

CONTEXT: Circulating lactate concentration is an important determinant of exercise tolerance. OBJECTIVE: To determine the role of hyperglycemia on lactate metabolism during exercise in type 1 diabetes (T1D). DESIGN: Protocol involved compared T1D participants and participants without diabetes (ND) at euglycemia [5.5mM] or hyperglycemia [9.2mM] in random order in T1D and at euglycemia in ND. SETTING: Clinical Research Unit, University of Virginia, Charlottesville, VA. PARTICIPANTS: 7 T1D and 7 ND. INTERVENTION: [1-13C] lactate infusion, exercise at 65% VO2max, euglycemia and hyperglycemia visits. MAIN OUTCOME MEASURE: Lactate turnover before, during and after 60 min of exercise at 65% VO2max. RESULTS: A two-compartment model with loss only from the peripheral compartment described lactate kinetics. Volume of distribution of the accessible compartment was similar between T1D and ND (p=0.76) and concordant to plasma volume (∼40ml/kg). Circulating lactate concentrations were higher (p<0.001) in T1D participants during exercise at hyperglycemia than euglycemia. Exercise induced lactate appearance did not differ (p=0.13) between hyperglycemia and euglycemia. However, lactate clearance was lower (p=0.03) during hyperglycemia than euglycemia in T1D. There were no differences in any of the above parameters between T1D and ND during euglycemia. CONCLUSIONS: Hyperglycemia modulates lactate metabolism during exercise by lowering lactate clearance leading to higher circulating lactate concentrations in T1D. This novel observation implies that exercise during hyperglycemia can lead to higher circulating lactate concentrations thus increasing the likelihood of reaching the lactate threshold sooner in T1D, and has high translational relevance for both providers and recreationally active people with Type 1 diabetes.

Prevalence of gestational diabetes mellitus & associated risk factors at a tertiary care hospital in Haryana.

BACKGROUND & OBJECTIVES: Prevalence of gestational diabetes mellitus (GDM) is known to vary widely depending on the region of the country, dietary habits, and socio-economic status. This study was undertaken to determine the prevalence of GDM and risk factors associated with it, in women attending an antenatal care (ANC) clinic at a tertiary care hospital in Haryana. METHODS: This study enrolled women, with their estimated gestational age between 24th and 28th week, attending antenatal care (ANC) clinic at a tertiary care hospital in Rohtak. After informing, women who consented to participate were given a standardized 2-h 75 g oral glucose tolerance test (OGTT). A proforma containing general information on demographic characteristics, socio-economic status, education level, parity, family history of diabetes and/or hypertension and past history of GDM was filled up. American Diabetes Association (ADA) criteria for 75 g 2-h OGTT was used for diagnosing GDM. RESULTS: A total of 607 women participated in the study and GDM was diagnosed in 43 (7.1%) women. A single abnormal value was observed in additional 66 (10.87%) women. On bivariate analysis risk factors found to be significantly associated with GDM were age, educational level, socio-economic status, pre-pregnancy weight and BMI, weight gain, acanthosis nigricans, family history of diabetes or hypertension and past history of GDM but on multivariate analysis only upper middle class and presence of acanthosis nigricans were found to be significantly associated with GDM. INTERPRETATION & CONCLUSIONS: The prevalence of GDM was found to be 7.1 per cent in a tertiary care hospital in Haryana. Appropriate interventions are required for control and risk factor modifications.

Altitude, temperature, and malaria vectors in Nainital and Udham Singh Nagar districts of Uttarakhand, India: an evidence-based study.

BACKGROUND & OBJECTIVES: The relationship between altitude, temperature and malaria are poorly understood. Hence, a study was undertaken at three sites of Udham Singh Nagar (erstwhile Nainital district) and Nainital district (Uttarakhand) during 2010- 11 for the generation of evidences in the context of potential threat of climate change. METHODS: Data on temperature and relative humidity (RH) were recorded through data-logger device in study villages at the altitudes of 166, 226 and 609 m were selected for detailed work. Mosquito collections were made fortnightly during 0600- 0800 hrs. Malaria incidence data were procured from concerned Primary Health Centres. RESULTS: The study provides evidences of decrease in temperature with increase in altitude, even within a district resulting in variation in temporal distribution of malaria vector. With the increase of 67 m altitude between plains and foothill village, there was a reduction in temperature to the tune of 1.1°C and with further increase in altitude of 416 m between foothill and hilly villages, the temperature decreased by 0.27°C. The difference in temperature at three altitudes affects the Transmission windows (TWs) of both Plasmodium vivax (Pv) and P. falciparum (Pf), and opening of TWs are inversely proportional to altitude. In the plains, the TW for Pv and Pf were open for 11 and 10 months respectively, while 10 and 9 months in the foothills and 9 and 8 months, respectively for both the parasites at hilly altitude. Comparison of malaria vectors in plains, foothills, and hilly villages showed that the availability of Anopheles culicifacies and An. fluviatilis decreased with an increase in altitude from foothills to hilly areas. INTERPRETATION & CONCLUSION: This study may be extrapolated to know the suitability of occurrence of malaria vectors and transmission of parasites at different altitudes from the viewpoint of temperature as limiting factor in unknown areas.

Nephroprotective and curative effects of Ficus religiosa latex extract against cisplatin-induced acute renal failure.

CONTEXT: Ficus religiosa L. (Moraceae) is widely planted in the tropics. Its chemical constituents include tannin, saponin gluanol acetate, ß-sitosterol, leucoanthocyanidin and leucoanthocyanin which are used for the treatment of pain, inflammation, impotence, menstrual disturbances, uterine tonic and urine related problems. OBJECTIVE: To determine the possible nephroprotective and curative effects of F. religiosa latex methanol extract against cisplatin induced acute renal failure. MATERIALS AND METHODS: Methanol extract was obtained by maceration process. Rats were divided in five groups. Group 1 was administered acacia (2% w/v) of 5 ml/kg throughout the experiment; group 2 was treated with single dose of cisplatin (5 mg/kg i.p.) on the 1st day; group 3 (200 mg/kg p.o.) of extract control for the 1st to 10th day, group 4 (200 mg/kg p.o.) of extract from the 1st to 10th day and a single dose of cisplatin (5 mg/kg, i.p.) on 11th day while group 5 received the same dose of cisplatin on day 1 and extract (200 mg/kg p.o.) from the 7th to 16th day. RESULTS: Phytochemical screening of the extract revealed the presence of glycoside, alkaloids, tannins (phenolic compounds), flavonoids and amino acids. The half maximal inhibitory concentration (IC50) values of the extract were 31.75 ± 0.12 and 18.35 ± 0.48 µg/ml, respectively. The cisplatin-treated group 2 showed significant changes; renal functions, biochemical parameters and histopathology were significantly (**p < 0.01) recovered by 200 mg/kg curative and protective groups. DISCUSSION AND CONCLUSION: These findings demonstrated that F. religiosa latex and constituents have excellent nephroprotective and curative activities and thus have great potential as a source for natural health products.

Investigation of the Asyogh's rectangular device for learning and memory testing in Wistar rats.

This study aimed to design Asyogh's rectangular device that is used for memory testing in rodents. It was found that scopolamine (3 mg/kg i.p.) and diazepam (1 mg/kg i.p.) caused significant memory deficits in rats, as evidenced by increased transfer latency times. However, these memory deficits were significantly reversed when the rats were pretreated with Donepezil. It further demonstrates that pretreated donepezil is able to effectively restore the memory deficits induced by scopolamine and diazepam, as indicated by the significant recovery in TLT. The present study showed that the device used to measure transfer latency time that was a valuable tool for assessing memory and cognitive function in rodents.

In Situ Measurement of Effective Gate Bias Voltage in Ionic Liquid-Gated Organic Field-Effect Transistors: Exploring Intrinsic Performance and Trap Density of States.

Electric double layer (EDL)-mediated transistors with ionic liquid (IL) gating have garnered substantial interest due to their exceptional properties, such as high transconductance and low-voltage operation, positioning them as promising candidates for organic electronics. In this study, we present an in situ measurement of effective gate bias voltage (VGS,eff) in IL-gated organic field-effect transistors (IL-OFETs) using a modified current-voltage measurement configuration. The results reveal a significant deviation between VGS,eff and the applied gate bias (VGS,app), indicating that the EDL at the gate/IL interface screens the applied voltage. It is observed that the screening effect varies depending on the specific cation and anion present in the IL. The evaluation of VGS,eff plays a pivotal role in understanding the intrinsic behavior of IL-OFETs and addresses the challenges associated with accurate performance assessment. Inherently, IL-OFETs demonstrate high transconductance, achieving values of approximately 9 mS while operating at a low threshold voltage of around 0.55 V. Through the acquisition of VGS,eff, we have successfully addressed the limitations impeding the numerical estimation of the trap density of states (trap DOS) in IL-OFETs. Remarkably, our calculations reveal an exceptionally low density of deep traps, which serves as a crucial factor contributing to the near-ideal subthreshold swing (61-68 mV dec-1) observed in IL-OFETs. Further investigations unveil the neutral electrical nature of the IL bulk during OFET operation, confirming the hypothesis that the applied gate bias voltage in electrolyte-gated OFETs drops across the EDLs formed at the interfaces. The impedance spectroscopic (IS) analysis confirms the low contact resistance (≈1 Ω·m) of IL-OFETs calculated using the transition voltage method. The IS analysis also reveals the low-transmissive nature of the IL/organic semiconductor interface. The knowledge gained from this study holds significant implications for realizing high-performance electrolyte-gated OFETs in various applications including digital electronics, energy storage, and sensing. By unraveling the factors influencing the device performance, such as VGS,eff and trap DOS, this research contributes to the advancement of organic electronics and paves the way for future developments in the field.

Conformationally locked sugar derivatives and analogues as potential neuraminidase inhibitors.

The influenza virus remains a major health concern for mankind because it tends to mutate frequently and cause high morbidity. Influenza prevention and treatment are greatly aided by the use of antivirals. One such class of antivirals is neuraminidase inhibitors (NAIs), effective against influenza viruses. A neuraminidase on the virus's surface serves a vital function in viral propogation by assisting in the release of viruses from infected host cells. Neuraminidase inhibitors are the backbone in stoping such virus propagation thus helps in the treatment of influenza viruses infections. Two NAI medicines are licensed globally: Oseltamivir (Tamiflu™) and Zanamivir (Relanza™). There are two molecules that have acquired Japanese approval recently: Peramivir and Laninamivir, whereas Laninamivir octanoate is in Phase III clinical trials. The need for novel NAIs is due to frequent mutations in viruses and the rise in resistance against existing medication. The NA inhibitors (NAIs) are designed to have (oxa)cyclohexene scaffolds (a sugar scaffold) to mimic the oxonium transition state in the enzymatic cleavage of sialic acid. This review discusses in details and comprises all such conformationally locked (oxa)cyclohexene scaffolds and their analogues which have been recently designed and synthesized as potential neuraminidase inhibitors, thus as antiviral molecules. The structure-activity relationship of such diverese molecules has also been discussed in this review.

Recent advances in the synthesis of new benzothiazole based anti-tubercular compounds.

This review highlights the recent synthetic developments of benzothiazole based anti-tubercular compounds and their in vitro and in vivo activity. The inhibitory concentrations of the newly synthesized molecules were compared with the standard reference drugs. The better inhibition potency was found in new benzothiazole derivatives against M. tuberculosis. Synthesis of benzothiazole derivatives was achieved through various synthetic pathways including diazo-coupling, Knoevenagel condensation, Biginelli reaction, molecular hybridization techniques, microwave irradiation, one-pot multicomponent reactions etc. Other than recent synthetic developments, mechanism of resistance of anti-TB drugs is also incorporated in this review. Structure activity relationships of the new benzothiazole derivatives along with the molecular docking studies of selected compounds have been discussed against the target DprE1 in search of a potent inhibitor with enhanced anti-tubercular activity.