Nitrogen-containing heterocyclic compounds: A ray of hope in depression?

Depression is not similar to daily mood fluctuations and temporary emotional responses to day-to-day activities. Depression is not a passing problem; it is an ongoing problem. It deals with different episodes consisting of several symptoms that last for at least 2 weeks. It can be seen for several weeks, months, or years. At its final stage, or can say, in its worst condition, it can lead to suicide. Antidepressants are used to inhibit the reuptake of the neurotransmitters by some selective receptors, which increase the concentration of specific neurotransmitters around the nerves in the brain. Drugs that are currently being used for the management of various types of depression include selective serotonin reuptake inhibitors, tricyclic antidepressants, atypical antidepressants, serotonin, noradrenaline reuptake inhibitors, etc. In this review, we have outlined different symptoms, causes, and recent advancements in nitrogen-containing heterocyclic drug candidates for the management of depression. This article highlights the various structural features along with the structure-activity relationship (SAR) of nitrogen-containing heterocyclics that play a key role in binding at target sites for potential antidepressant action. The in silico studies were carried out to determine the binding interactions of the target ligands with the receptor site to determine the potential role of substitution patterns at core pharmacophoric features. This article will help medicinal chemists, biochemists, and other interested researchers in identifying the potential pharmacophores as lead compounds for further development of new potent antidepressants.

Pyrazoline Derivatives as Promising MAO-A Targeting Antidepressants: An Update.

Depression is one of the key conditions addressed by the Mental Health Gap Action Programme (mhGAP) of WHO that can lead to self-harm and suicide. Depression is associated with low levels of neurotransmitters, which eventually play a key role in the progression and development of mental illness. The nitrogen-containing heterocyclic compounds exhibit the most prominent pharmacological profile as antidepressants. Pyrazoline, a dihydro derivative of pyrazole, is a well-known five-membered heterocyclic moiety that exhibits a broad spectrum of biological activities. Many researchers have reported pyrazoline scaffold-containing molecules as potential antidepressant agents with selectivity for monoamine oxidase enzyme (MAO) isoforms. Several studies indicated a better affinity of pyrazoline-based moiety as (monoamine oxidase inhibitors) MAOIs. In this review, we have focused on the recent advancements (2019-2023) in the development of pyrazoline-containing derivatives exhibiting promising inhibition of MAO-A enzyme to treat depression. This review provides structural insights on pyrazoline-based molecules along with their SAR analysis, in silico exploration of binding interactions between pyrazoline derivatives and MAO-A enzyme, and clinical trial status of various drug molecules against depression. The in-silico exploration of potent pyrazoline derivatives at the active site of the MAOA enzyme will provide further insights into the development of new potential MAO-A inhibitors for the treatment of depression.

Exploration of oxadiazole clubbed benzhydrylpiperazine pharmacophoric features as structural feature for antidepressant activity: In vitro, in vivo and in silico analysis.

Arylpiperazine clubbed various heterocyclic molecules present potential pharmacophoric structural features for the development of psychoactive drugs. There are various CNS active molecules possessing arylpiperazine moiety in their pharmacophore approved by USFDA. In the current study, we have explored the benzhydrylpiperazine moiety clubbed with various substituted oxadiazole moieties (AP1-12) for their monoamine oxidase (MAO) inhibition and antidepressant potential. Compounds AP3 and AP12 exhibited highly potent and selective MAO-A inhibition with IC50 values of 1.34 ± 0.93 µM and 1.13 ± 0.54 µM, respectively, and a selectivity index of 10- and 13-folds, respectively. Both the compounds displayed reversible binding character at the active site of MAO-A. In further in vivo evaluation, both the compounds AP3 and AP12 displayed potential antidepressant-like character in FST and TST studies via significantly reduced immobility time in comparison to non-treated animals. These compounds displayed no cytotoxicity in SH-SY5Y cell lines, which indicates that these compounds are safe for further evaluation. In silico studies reveal that synthesized compounds possess drug-likeness with minimal to no toxicity. In silico studies were conducted to understand the binding interactions and stability of compounds at the binding pocket of enzyme and observed that both the best compounds fit well at the active site of MAO-A lined by amino acid residues Tyr69, Asn181, Phe208, Ile335, Leu337, Phe352, and Tyr444 similar to standard MAO-A inhibitor clorgiline. The molecular dynamic studies demonstrated that AP3 and AP12 formed quite a stable complex at the active site of MAO-A and did not break under small abruption forces. The favourable binding interactions and appropriate ADMET properties present the benzhydrylpiperazine clubbed oxadiazole pharmacophoric features as a potential structural skeleton for further clinical evaluation and development of a new antidepressant drug molecule.

Paradigms and Success Stories of Natural Products in Drug Discovery Against Neurodegenerative Disorders (NDDs).

Neurodegenerative disorders (NDDs) are multifaceted complex disorders that have put a great health and economic burden around the globe nowadays. The multi-factorial nature of NDDs has presented a great challenge in drug discovery and continuous efforts are in progress in search of suitable therapeutic candidates. Nature has a great wealth of active principles in its lap that has cured the human population since ancient times. Natural products have revealed several benefits over conventional synthetic medications and scientists have shifted their vision towards exploring the therapeutic potentials of natural products in the past few years. The structural mimicking of natural compounds to endogenous ligands has presented them as a potential therapeutic candidate to prevent the development of NDDs. In the presented review, authors have summarized demographical facts about various NDDs including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and various types of sclerosis in the brain. The significant findings of new active principles of natural origin along with their therapeutic potentials on NDDs have been included. Also, a description of clinical trials and patents on natural products has been enlisted in this compilation. Although natural products have shown promising success in drug discovery against NDDs, still their use is associated with several ethical issues which need to be solved in the upcoming time.

In-Silico Investigation of Ginseng Phytoconstituents as Novel Therapeutics Against MAO-A.

BACKGROUND: Ginseng (Panax ginseng) is a herb of medicinal and nutritional importance. Ginseng has been used since ancient times for the treatment of numerous ailments as it has many therapeutic properties. Several phytoconstituents are present in Panax ginseng that possess a variety of beneficial pharmacological properties. OBJECTIVE: To explore the potential of phytoconstituents of Panax ginseng in the treatment of depression, a molecular modeling technique was utilized targeting monoamine oxidase-A (MAOA). METHODS: A total of sixty-one phytoconstituents of ginseng were drawn with the help of ChemBioDraw Ultra 12.0 software and PDBs for MAO-A enzyme were retrieved from the RCSB PDB database. The prepared ligands were screened for MAO-A properties using the software Molegro Virtual Docker (MVD 2010.4.1.0). All the prepared ligands were evaluated for drug-likeliness properties using Swiss ADME. RESULT: Among the docking studies of 60 Ginseng phytochemicals including one standard, 15 phytoconstituents with the highest dock score and better binding interactions were selected further for absorption, distribution, metabolism and excretion (ADME) studies. Stachyose (-227.287, 17 interactions), Raffinose (-222.157, 14 interactions), and Ginsenoside Rg1 (-216.593, 10 interactions) were found to possess better interactions as compared to Clorgyline taken as a standard drug. CONCLUSION: Stachyose was found to be the most potent inhibitor of MAO-A enzyme under investigation and can be a potential lead molecule for the development of newer phytochemical-based treatment of depression.

Imidazoles as Serotonin Receptor Modulators for Treatment of Depression: Structural Insights and Structure-Activity Relationship Studies.

Serotoninergic signaling is identified as a crucial player in psychiatric disorders (notably depression), presenting it as a significant therapeutic target for treating such conditions. Inhibitors of serotoninergic signaling (especially selective serotonin reuptake inhibitors (SSRI) or serotonin and norepinephrine reuptake inhibitors (SNRI)) are prominently selected as first-line therapy for the treatment of depression, which benefits via increasing low serotonin levels and norepinephrine by blocking serotonin/norepinephrine reuptake and thereby increasing activity. While developing newer heterocyclic scaffolds to target/modulate the serotonergic systems, imidazole-bearing pharmacophores have emerged. The imidazole-derived pharmacophore already demonstrated unique structural characteristics and an electron-rich environment, ultimately resulting in a diverse range of bioactivities. Therefore, the current manuscript discloses such a specific modification and structural activity relationship (SAR) of attempted derivatization in terms of the serotonergic efficacy of the resultant inhibitor. We also featured a landscape of imidazole-based development, focusing on SAR studies against the serotoninergic system to target depression. This study covers the recent advancements in synthetic methodologies for imidazole derivatives and the development of new molecules having antidepressant activity via modulating serotonergic systems, along with their SAR studies. The focus of the study is to provide structural insights into imidazole-based derivatives as serotonergic system modulators for the treatment of depression.

Design, Synthesis, Molecular Docking, and Biological Evaluation of Isatin-Based Fused Heterocycles As Epidermal Growth Factor Receptor Inhibitors.

A series of isatin-based fused heterocycles were designed, synthesized, and evaluated for anticancer activity against four cancer cell lines: MCF-7, MDA-MB-231, A549, and HL-60. Among them, Q3 and T4 were found to be potent anticancer agents. Furthermore, two compounds Q3 and T4 were selected for epidermal growth factor receptor (EGFR) inhibitory activity. Two compounds Q3 and T4 were found to be most potent EGFR inhibitors with IC50 of 0.22 ± 0.10 and 0.19 ± 0.07 µM. The EGFR inhibitory activity of standard drug erlotinib was 0.08 ± 0.02 µM. Structural Activity Relationship studies showed that electronegative atoms were necessary for EGFR inhibitory potential. Finally, molecular docking studies were carried out to check the binding pattern of synthesized derivatives with the adenosine triphosphate (ATP) binding site of EGFR and results revealed that compounds Q3 (-9.2 kcal/mol) and T4 (-8.9 kcal/mol) exhibited better binding affinity than reference drug erlotinib (-7.3 kcal/mol).

A Compiled Update on Nutrition, Phytochemicals, Processing Effects, Analytical Testing and Health Effects of Chenopodium album: A Non-Conventional Edible Plant (NCEP).

Bathua (Chenopodium album) is a rich source of extensive-ranging nutrients, including bio-active carbohydrates, flavonoids and phenolics, minerals, and vitamins that translate to countless health benefits such as anticancer, antidiabetic, anti-inflammatory, antimicrobial, and antioxidant activity. Ascaridole, an important phytoconstituent present in aerial parts of the plant, contributes to its anthelmintic property. Even with vast historical use and significant health benefits, its renown has not spread, and utilization has significantly decreased in recent decades. Gradually, the plant has become known under the name of Non-conventional edible plant (NCEP). This compilation is prepared to bring out the plant under the spotlight for further research by foregrounding previous studies on the plant. Scientific research databases, including PubMed, Google Scholar, Scopus, SpringerLink, ScienceDirect, and Wiley Online, were used to fetch data on C. album. This review offers over up-to-date knowledge on nutritious values, phytochemical composition, volatile compounds, as well as health benefits of C. album. The ethnobotanical and ethnomedicinal uses of the plant in India and other parts of the world are deliberately discussed. Scrutinizing the reported literature on C. album reveals its powerful nutrient composition advantageous in the development of food products. The impact of various cooking and processing methods on the nutritional profile and bioavailability are discussed. The future perspectives with regards to the potential for food and nutraceutical products are critically addressed. This review proves the necessity of breakthrough research to investigate the pharmacology and safety of phytochemicals and nutraceutical development studies on the C. album.

Design, synthesis and biological evaluation of oxadiazole clubbed piperazine derivatives as potential antidepressant agents.

Piperazine derivatives have been of great interest to medicinal chemists in the development of antidepressant drugs due to their distinct molecular and structural features along with their pharmacological profile. In this study, we have designed and synthesized a series of 10 compounds of piperazine clubbed oxadiazole derivatives (5a-j) and screened for their MAO inhibitory activity. Compound 5f and 5 g were found to be the most potent MAO-A inhibitors of the series with IC50 values of 0.96 ± 0.04 µM µM and 0.81 ± 0.03 µM, respectively with a selectivity index of 18-folds and 9-folds over MAO-B isoform. The compounds were found to be reversible inhibitors of MAO-A with no cytotoxicity against SH-SY5Y neuronal cells. The compounds also displayed good antioxidant activity. Further, in vivo TST studies revealed that both the compounds 5f and 5 g possessed good anti-depressant-like activity and reduced the immobility time significantly although were found inactive in FST studies. The molecular docking studies revealed that both compounds fit well at the active site of MAO-A enzyme as similar to clorgyline and form a stable complex. The results were confirmed via molecular dynamic studies which demonstrate the stable complex formation between MAO-A and 5f & 5 g. The appropriate drug-like characteristics with favourable ADMET profile, these molecules presented this piperazine clubbed oxadiazole structural framework as a key pharmacophore for the development of new antidepressant molecules along with strong candidature for further clinical investigations.

Recent updates on structural insights of MAO-B inhibitors: a review on target-based approach.

Parkinson's disease is a neurodegenerative disorder characterized by slow movement, tremors, and stiffness caused due to loss of dopaminergic neurons caused in the brain's substantia nigra. The concentration of dopamine is decreased in the brain. Parkinson's disease may be happened because of various genetic and environmental factors. Parkinson's disease is related to the irregular expression of the monoamine oxidase (MAO) enzyme, precisely type B, which causes the oxidative deamination of biogenic amines such as dopamine. MAO-B inhibitors, available currently in the market, carry various adverse effects such as dizziness, nausea, vomiting, lightheadedness, fainting, etc. So, there is an urgent need to develop new MAO-B inhibitors with minimum side effects. In this review, we have included recently studied compounds (2018 onwards). Agrawal et al. reported MAO-B inhibitors with IC50 0.0051 µM and showed good binding affinity. Enriquez et al. reported a compound with IC50 144 nM and bind with some critical amino acid residue Tyr60, Ile198, and Ile199. This article also describes the structure-activity relationship of the compounds and clinical trial studies of related derivatives. These compounds may be used as lead compounds to develop potent compounds as MAO-B inhibitors.

Design, Synthesis, and Biological Evaluation of Novel Dihydropyrimidinone Derivatives as Potential Anticancer Agents and Tubulin Polymerization Inhibitors.

The severity and prevalence of cancer in modern time are a huge global health burden. Continuous efforts are being made toward the development of newer therapeutic candidates to treat and manage this ailment. The dihydropyrimidinone scaffold is one of the key nuclei that have been highly explored and investigated against cancer. It has the potential to combat the consequences of cancer by interacting with several biological targets. Tubulin polymerization inhibition is one such strategy to prevent the progression of cancer. In the presented work, we have synthesized a series of sixteen dihydropyrimidinone derivatives by following a rational drug design. The synthesized compounds have been characterized by 1H NMR and 13C NMR and were further evaluated for cytotoxic activity against breast cancer cell lines (MCF-7 and MDA-MB-231), lung cancer cell lines (A549), and colon cancer cell lines (HCT-116). Compounds 5D and 5P were found most potent and revealed a better cytotoxic activity compared with the standard drug colchicine. Furthermore, the tubulin polymerization inhibition assay revealed that compound 5D showed better inhibition than colchicines, whereas compound 5P revealed an almost equal inhibition to that of colchicine. Furthermore, to investigate the possible mode of action and binding patterns, compounds 5P and 5D were subjected to molecular docking against tubulin (Protein Data Bank ID: ISA0). The results showed that compounds revealed significant interactions and were well occupied inside the cavity of tubulin. The compounds 5D and 5P may serve as new leads in drug development against cancer.

Tivozanib: A New Hope for Treating Renal Cell Carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is a diverse collection of malignancies with varying histological characteristics, molecular changes, prognosis, and therapeutic response. Tivozanib was first approved in March 2021 by USFDA with the brand name Fotivda. Tivozanib hydrochloride monohydrate is an oral medication that is used to treat relapsed or refractory renal cell carcinoma. OBJECTIVE: In this review, we explain renal cell carcinoma and its different types of treatment by the anti-renal carcinoma drugs. METHODS: A comprehensive literature search was conducted in the relevant databases, like ScienceDirect, PubMed, ResearchGate, and Google Scholar, to identify the studies. CONCLUSION: Tivozanib is an oral VEGFR-1, VEGFR-2, and VEGFR-3 tyrosine kinase inhibitor that is extremely selective and powerful. It has much less affinity for other receptor tyrosine kinases than multi-targeted TKIs now in clinical use. Because of its long half-life in circulation, it may be able to block VEGFRs more consistently. Doserelated controllable hypertension is its most commonly seen drug-related side event. Fatigue, hoarseness, and diarrhea, which are all common side effects, are not dose-related. Because of its target specificity, tivozanib can work well with other medications that have low side effects. Blocking both the VEGF and mTOR signaling pathways at the same time provides the benefit of synergistic antitumor efficacy while also preventing treatment resistance. Thus, overall we can say that the drug tivozanib is suitable for treatment in patients with renal cell carcinoma and can be investigated in multi-center clinical trials.

US-FDA Approved Drugs in 2020 and 2021: A Review.

INTRODUCTION: Throughout the years, the disruption caused by COVID-19 continues to pose an excess of challenges for the pharmaceutical industry. Throughout the entire year, questions were raised that does COVID-19 have a negative impact on new drug approvals. However, the answer to those questions was a 'big no'. METHODS: We propose a compilation and analysis of around 100 medications, including small new molecular entities (NMEs), approved by the US Food and Drug Administration for the years 2020 and 2021. Novel drug discovery is crucial for pharmaceutical research and development as well as patient care. The only possible way to achieve this crucial goal is to repurpose current medications that may have anticipated effects as possible candidates. The availability of new drugs and biological products often means new treatment options for patients and advances in health care. RESULTS: Around 40% of the drugs were approved for various types of cancers. Other major therapeutic areas that were focused on were neurological products (around 17%), infectious diseases (13-15%), and cardiovascular disorders (7-8%). Various new products were approved for rare diseases (58-60%). This study aimed to discover a pattern in FDA medicine approvals during the last two decades. CONCLUSION: This data shows that anticancer medicines and biologics are receiving increased attention in research. With a bigger number of biologically derived medications being produced, the price could rise much higher. FDA should embrace innovative techniques that will stimulate the industry to enhance research and development of novel compounds or medications that can deliver considerable improvements over existing ones. To put it briefly, FDA had to update our approach to regulation as a whole in order to effectively develop the types of technologies that are becoming available. Modernizing medical product review programmes is a part of this. These initiatives are part of the Medical Innovation Access Plan.

p53 as a potential target for treatment of cancer: A perspective on recent advancements in small molecules with structural insights and SAR studies.

Cancer represents one of the world's biggest hazardous diseases. p53 is the uttermost researched tumour suppressor protein. It is commonly considered the "guardian of the genome," performing a critical function in genetic stability maintenance through controlling the cell cycle, programmed cell death, DNA repair, aging, and angiogenesis. The abnormalities in p53 lead to genetic instability and plays a significant role in carcinogenesis. The role of p53 in tumour suppression is emphasized in addition by the observation that primary silencing with this protein occurred in more than 50% of cancers. MDM2, p53, and the p53-MDM2 connections are well-known targets for the prevention and treatment of cancer. Moreover, in tumors with wild-type p53, their efficacy is decreased due to MDM2 enlargement or by the gradual decrease of MDM2 blocker ARF. As a result, improving p53 activity in cancerous cells provides a promising anticancer strategy. Various techniques are now being investigated, and addressing the p53-MDM2 interaction had also evolved as a potentially feasible strategy for contending with tumors. Both p53 and MDM2, interact via an autoregulation response signal: p53 activity induces MDM2 transcription, which in response interacts with p53's N-terminal transactivation domain, inhibiting its transcriptional activity. This article provides information on the current scenario of anti-tumor activities, with a particular emphasis on structure-activity relationship characteristics (SAR) against the p53-MDM2 to treat cancer. The primary purpose of this review is to cover recent advancements in the creation and testing of anticancer drugs that target the p53-MDM2 structure. This review contains different heterocyclic moieties which show significant results toward cancer. A mechanistic route is shown here, demonstrating both normal and malignant conditions via several stressed factors. Several compounds entered clinical trials as p53-MDM2 inhibitors for the treatment of cancer.

Design, synthesis of 1,2,4-triazine derivatives as antidepressant and antioxidant agents: In vitro, in vivo and in silico studies.

The novel series of substituted-N-(5,6-diphenyl-1,2,4-triazin-3-yl) benzamides (R: 1-12) were designed, synthesized and evaluated for in-vitro and in-vivo antidepressant-like activity. In MAO-A inhibition assay, compound R: 5 and R: 9 displayed most potent activity with IC50 = 0.12 and 0.30 µM. R: 5 and R: 9 were also evaluated for in-vivo antidepressant using FST and TST. In both models, the test samples R: 5 and R: 9 showed noteworthy antidepressant effect. R: 5 showed 46.48 % and 45.96 % reduction in immobility in FST and TST respectively at dosage of 30 mg/kg (p.o). Whereas compound R: 9 reduced the immobility time by 52.76 % and 47.14 % as compared to control in FST and TST, respectively at same dosage. Both the compounds were also tested for behavioural study using actophotometer and grip tests. None of compounds exhibited decrease in locomotor activity. Further, these compounds were subjected to in silico studies to determine their ADME properties along with binding energies and binding orientions. In ADME studies none of the compounds violated the Lipinski rule and all other parameters were also within the acceptable ranges. In docking study R: 5 (-10.7) and R: 9 (-10.4) were also displayed highest docking score. These encouraging results present the pharmacophoric features of substituted-N-(5,6-diphenyl-1,2,4-triazin-3-yl) benzamides as interesting lead for further development of new antidepressant drug molecules.

Role of sodium dependent SLC13 transporter inhibitors in various metabolic disorders.

The sodium dependent SLC13 family transporters comprise of five genes SLC13A1, SLC13A2 (NaDC1), SLC13A3 (NaDC3), SLC13A4 and SLC13A5 (NaCT). Among them, NaDC1, NaDC3 and NaCT are sodium dependent transporters belonging to family of dicarboxylates (succinate, malate, α-ketoglutarate) and tricarboxylates (citrate). The mouse and the human NaCT structures have still not been crystallized, therefore structural information is taken from the related bacterial transporter of VcINDY. Citrate in the cytosol works as a precursor for the fatty acid synthesis, cholesterol, and low-density lipoproteins. The excess citrate from the matrix is translocated to the cytosol for fatty acid synthesis through these transporters and thus controls the energy balance by downregulating the glycolysis, tricarboxylic acid (TCA), and fatty acid breakdown. These transporters play an important role in regulating various metabolic diseases including cancer, diabetes, obesity, fatty liver diseases and CNS disorders. These di and tricarboxylate transporters are emerging as new targets for metabolic disorders such as obesity and diabetes. The mutation in the function of the NaCT causes several neurological diseases including neonatal epilepsy and impaired brain development whereas mutation of genes coding for citrate transport present in the liver may provide positive effect. Therefore, continued efforts from the earlier work on citrate transporters are required for the development of citrate inhibitors. This review discusses the structure, function, and regulation of the NaCT transporter. The review also highlights citrate role in diagnosing diseases such as cancer, diabetes, fatty liver, and diabetes. The therapeutic perspective of synthetic inhibitors against NaCT transporters is succinctly summarized.

Design, Synthesis, and Pharmacological Evaluation of N-Propargylated Diphenylpyrimidines as Multitarget Directed Ligands for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD), a multifactorial complex neural disorder, is categorized with progressive memory loss and cognitive impairment as main clinical features. The multitarget directed ligand (MTDL) strategy is explored for the treatment of multifactorial diseases such as cancer and AD. Herein, we report the synthesis and screening of 24 N-propargyl-substituted diphenylpyrimidine derivatives as MTDLs against acetylcholine/butyrylcholine esterases and monoamine oxidase enzymes. In this series, VP1 showed the most potent MAO-B inhibitory activity with an IC50 value of 0.04 ± 0.002 µM. VP15 with an IC50 value of 0.04 ± 0.003 µM and a selectivity index of 626 (over BuChE) displayed the most potent AChE inhibitory activity in this series. In the reactive oxygen species (ROS) inhibition studies, VP1 reduced intercellular ROS levels in SH-SY5Y cells by 36%. This series of compounds also exhibited potent neuroprotective potential against 6-hydroxydopamine-induced neuronal damage in SH-SY5Y cells with up to 90% recovery. In the in vivo studies in the rats, the hydrochloride salt of VP15 was orally administered and found to cross the blood-brain barrier and reach the target site. VP15·HCl significantly attenuated the spatial memory impairment and improved the cognitive deficits in the mice. This series of compounds were found to be irreversible inhibitors and showed no cytotoxicity against neuronal cells. In in silico studies, the compounds attained thermodynamically stable orientation with complete occupancy at the active site of the receptors. Thus, N-propargyl-substituted diphenylpyrimidines displayed drug-like characteristics and have the potential to be developed as MTDLs for the effective treatment of AD.

Seroprevalence of anti SARS-CoV-2 IgG antibodies among adults in Jammu district, India: A community-based study.

Background & objectives: Serology testing is essential for immunological surveillance in the population. This serosurvey was conducted to ascertain the cumulative population immunity against SARS-CoV-2 among adults in Jammu district and to understand the association of seropositivity with sociodemographic and clinical correlates. Methods: On September 30 and October 1, 2020, a household survey was done in 20 villages/wards chosen from 10 health blocks in district Jammu, India. Demographic, clinical and exposure information was collected from 2000 adults. Serum samples were screened for IgG antibodies using COVID Kavach MERILISA kit. Tests of association were used to identify risk factors associated with IgG positivity. Crude odds ratio with 95 per cent confidence intervals (CIs) was calculated during univariate analysis followed by logistic regression. Results: Overall adjusted seroprevalence for SARS-CoV-2 was 8.8 per cent (95% CI: 8.78-8.82); it varied from 4.1 per cent in Chauki choura to 16.7 per cent Pallanwalla across 10 blocks in the district. Seropositivity was observed to be comparatively higher in 41-50 and 61-70 yr age groups, among males and in rural areas. Fever, sore throat, cough, dyspnoea, myalgias, anosmia, ageusia, fatigue, seizures, history of exposure, medical consultation, hospitalization and missing work showed significant association with seropositivity on univariate analysis. On logistic regression, only sore throat, myalgia and missing work showed significant adjusted odds of IgG positivity. Extrapolation to adult population suggested that exposure to SARS-CoV-2 was 14.4 times higher than reported cases, translating into Infection fatality rate of 0.08 per cent. Interpretation & conclusions: Since a major part of population was immunologically naive, all efforts to contain COVID-19 need to be vigorously followed while these baseline results provide an important yardstick to monitor the trends of COVID-19 and guide locally appropriate control strategies in the region.