Mycosporine-Like Amino Acids as a Potential Inhibitor of Tyrosinase-Related Protein 1: Computational Screening, Pharmacokinetics, and Molecular Dynamics Simulation.

Melanin is the major pigment responsible for the coloring of mammalian skin, hair, and eyes to defend against ultraviolet radiation. However, excessive melanin production has resulted in numerous types of hyperpigmentation disorders. Tyrosinase-related protein 1 (TYRP1) is a transmembrane glycoprotein enzyme found in many organisms, including humans, that plays an important role in melanogenesis. Thus, controlling the enzyme activity of TYRP1 with tyrosinase inhibitors is a vital step in the treatment of hyperpigmentation problems in humans. In the present investigation, virtual screening, pharmacokinetics, drug docking, and molecular dynamics (MD) simulation were used to find the most potent drug as an inhibitor of TYRP1 to effectively treat hyperpigmentation disorder. The 3D structure of TYRP1 was retrieved from the Protein Data Bank (PDB) database (PDB ID: 5M8M) and validated by the Ramachandran plot. Pharmacokinetics and drug-likeness showed that mycosporine 2 glycine (M2G) and shinorine (SHI) were the best compounds over other ligands in the same (P-1) structural pose. However, MD simulations of the M2G showed the highest CDOCKER interaction energy (-45.182 kcal/mol) and binding affinity (-65.0529 kcal/mol) as compared to SHI and reference drugs. The molecular binding modes RMSD and RMSF plots have exhibited more relevance to the M2G ligand in comparison to other drug ligands. The bioactivity and ligand efficiency profiles revealed that M2G is the most effective compound as a TYRP1 inhibitor. Thus, M2G could be used as a most effective drug for developing valuable sunscreen products to cure hyperpigmentation-related diseases.

Virtual Screening, Docking, and Designing of New VEGF Inhibitors as Anti-cancer Agents.

BACKGROUND: VEGFR-2 tyrosine kinase inhibitors are receiving a lot of attention as prospective anticancer medications in the current drug discovery process. OBJECTIVE: This work aims to explore the PubChem library for novel VEGFR-2 kinase inhibitors. 1H-Indazole-containing drug AXITINIB, or AG-013736 (FDA approved), is chosen as a rational molecule for drug design. This scaffold proved its efficiency in treating cancer and other diseases as well. METHODS: The present study used the virtual screening of the database, protein preparation, grid creation, and molecular docking analyses. RESULTS: The protein was validated on different parameters like the Ramachandran plot, the ERRAT score, and the ProSA score. The Ramachandran plot revealed that 92.1% of the amino acid residues were located in the most favorable region; this was complemented by an ERRAT score (overall quality factor) of 96.24 percent and a ProSA (Z score) of -9.24 percent. The Lipinski rule of five was used as an additional filter for screening molecules. The docking results showed values of binding affinity between -14.08 and -12.34 kcal/mol. The molecule C1 showed the highest docking value of -14.08 Kcal/mol with the maximum number of strong H-bonds by -NH of pyridine to amino acid Cys104 (4.22Å), -NH of indazole to Glu108 (4.72), and Glu70 to bridge H of -NH. These interactions are similar to Axitinib docking interactions like Glu70, Cys104, and Glu102. The docking studies revealed that pi-alkyl bonds are formed with unsubstituted pyridine, whereas important H-bonds are observed with different substitutions around -NH. Based on potential findings, we designed new molecules, and molecular docking studies were performed on the same protein along with ADMET studies. The designed molecules (M1-M4) also showed comparable docking results similar to Axitinib, along with a synthetic accessibility score of less than 4.5. CONCLUSION: The docking method employed in this work opens up new possibilities for the design and synthesis of novel compounds that can act as VEGFR-2 tyrosine kinase inhibitors and treat cancer.

Structure-guided engineering of biased-agonism in the human niacin receptor via single amino acid substitution.

The Hydroxycarboxylic acid receptor 2 (HCA2), also known as the niacin receptor or GPR109A, is a prototypical GPCR that plays a central role in the inhibition of lipolytic and atherogenic activities. Its activation also results in vasodilation that is linked to the side-effect of flushing associated with dyslipidemia drugs such as niacin. GPR109A continues to be a target for developing potential therapeutics in dyslipidemia with minimized flushing response. Here, we present cryo-EM structures of the GPR109A in complex with dyslipidemia drugs, niacin or acipimox, non-flushing agonists, MK6892 or GSK256073, and recently approved psoriasis drug, monomethyl fumarate (MMF). These structures elucidate the binding mechanism of agonists, molecular basis of receptor activation, and insights into biased signaling elicited by some of the agonists. The structural framework also allows us to engineer receptor mutants that exhibit G-protein signaling bias, and therefore, our study may help in structure-guided drug discovery efforts targeting this receptor.

Studies on α-amylase inhibition by acarbose and quercetin using fluorescence, circular dichroism, docking, and dynamics simulations.

This study looked at the effects of acarbose (ACA) and quercetin (QUE) on α-amylase activity, employing QUE and ACA to measure enzyme activity. The study observed that both drugs suppressed α-amylase activity, with greater inhibition reported at higher concentrations. The use of tryptophan residues as an intrinsic fluorescence probe permitted the observation of conformational changes in α-amylase, with CD measurements utilized to explore the secondary structure in the presence of QUE and ACA. Docking studies revealed an effective interaction between α-amylase, quercetin and acarbose, with a higher binding energy. Finally, a trajectory analysis was done to establish the stability and volatility of these complexes. These findings have potential significance for the development of new α-amylase-related therapeutics.

Genetic and in silico analysis of Indian sporadic young onset patient with amyotrophic lateral sclerosis.

Background: Amyotrophic lateral sclerosis (ALS) is an old onset devastating neurodegenerative disorder. Young-onset ALS cases especially sporadic ones who are between 25 and 45 years are rarely affected by the disease. Despite the identification of numerous candidate genes associated with ALS, the etiology of the disease remains elusive due to extreme genetic and phenotypic variability. The advent of affordable whole exome sequencing (WES) has opened new avenues for unraveling the disease's pathophysiology better. Methods and results: We aimed to determine the genetic basis of an Indian-origin, young onset sporadic ALS patient with very rapid deterioration of the disease course without any cognitive decline who was screened for mutations in major ALS candidate genes by WES. Variants detected were reconfirmed by Sanger sequencing. The clinicopathological features were investigated and two heterozygous missense variants were identified: R452W, not previously associated with ALS, present in one of the four conserved C terminal domains in ANXA11 and R208W in SIGMAR1, respectively. Both of these variants were predicted to be damaging by pathogenicity prediction tools and various in silico methods. Conclusion: Our study revealed two potentially pathogenic variants in two ALS candidate genes. The genetic makeup of ALS patients from India has been the subject of a few prior studies, but none of them examined ANXA11 and SIGMAR1 genes so far. These results establish the framework for additional research into the pathogenic processes behind these variations that result in sporadic ALS disease and further our understanding of the genetic makeup of Indian ALS patients.

Laboratory Assessment of Molluscicidal Activities of Cannabis sativa, Acacia nilotica, and Tinospora cordifolia Against Snail Host of Fasciola spp.

Background: The potential molluscicidal extracts, obtained from indigenous plants Cannabis sativa, Acacia nilotica, and Tinospora cordifolia, were tested for toxicity against freshwater pulmonate snail Lymnaea acuminata, an intermediate host of Fasciola hepatica. The organic extracts had a significant effect on young snails. Materials and Methods: All organic extracts and column-purified fractions gave median lethal concentrations (19-100.05 mg/L; 24 h) that fell well within the threshold level of 100 mg/L, set for a potential molluscicide by the World Health Organization. Results: The toxicity of T. cordifolia stem acetone extract (96 h LC50: 16.08 mg/L) was more pronounced compared with C. sativa leaf ethanol extract (96 h LC50: 16.32 mg/L) and A. nilotica leaf ethanol extract (96 h LC50: 24.78 mg/L). ß-caryophyllene, gallic acid, and berberine were characterized and identified as active molluscicidal components. Co-migration of ß-caryophyllene (retardation factor [Rf] 0.95), gallic acid (Rf 0.30), and berberine (Rf 0.23) with column-purified parts of Cannabis sativa, Acacia nilotica, and Tinospora cordifolia on thin-layer chromatography demonstrates same Rf value, that is, 0.95, 0.30, and 0.23, respectively. Conclusion: This study indicates that these extracts thus represent potential plant-derived molluscicides that are worthy of further investigations.

Review on computer-assisted biosynthetic capacities elucidation to assess metabolic interactions and communication within microbial communities.

Microbial communities thrive through interactions and communication, which are challenging to study as most microorganisms are not cultivable. To address this challenge, researchers focus on the extracellular space where communication events occur. Exometabolomics and interactome analysis provide insights into the molecules involved in communication and the dynamics of their interactions. Advances in sequencing technologies and computational methods enable the reconstruction of taxonomic and functional profiles of microbial communities using high-throughput multi-omics data. Network-based approaches, including community flux balance analysis, aim to model molecular interactions within and between communities. Despite these advances, challenges remain in computer-assisted biosynthetic capacities elucidation, requiring continued innovation and collaboration among diverse scientists. This review provides insights into the current state and future directions of computer-assisted biosynthetic capacities elucidation in studying microbial communities.

Computer-assisted biosynthetic capacities elucidation accelerates our ability to interpret microbial interactions, allowing us to understand better and establish a balance within ecosystems.

In Silico Structural and Functional Insight into the Binding Interactions of the Modeled Structure of Watermelon Urease with Urea.

Urease (EC 3.5.1.5) is an amidohydrolase. This nickel-dependent metalloenzyme converts urea into NH3 and CO2. Despite their vital role in plants, the structure and function of watermelon (Citrullus lanatus) urease are unknown. We used third- and fourth-generation gene prediction algorithms to annotate the C. lanatus urease sequence in this investigation. The solved urease structure from Canavalia ensiformis (PDB ID: 4GY7) was utilized as a template model to identify the target 3-D model structure of the unknown C. lanatus urease for the first time. Cluretox, the C. lanatus urease intrinsic disordered area identical to Jaburetox, was also found. The C. lanatus urease structure was docked with urea to study atom interaction, amino acid interactions, and binding analyses in the urease-urea complex at 3.5 Å. This study found that amino acids His517, Gly548, Asp631, Ala634, Thr569, His543, Met635, His407, His490, and Ala438 of C. lanatus urease bind urea. To study the molecular basis and mode of action of C. lanatus urease, molecular dynamics simulation was performed and RMSD, RMSF, Rg, SAS, and H-bond analyses were done. The calculated binding free energy (ΔG) for the urea-urease complex at 100 ns using the MM/PBSA method is -7.61 kJ/mol. Understanding its catalytic principles helps scientists construct more efficient enzymes, tailor fertilization to boost agricultural output, and create sustainable waste management solutions.

Molecular insights into atypical modes of ß-arrestin interaction with seven transmembrane receptors.

ß-arrestins (ßarrs) are multifunctional proteins involved in signaling and regulation of seven transmembrane receptors (7TMRs), and their interaction is driven primarily by agonist-induced receptor activation and phosphorylation. Here, we present seven cryo-electron microscopy structures of ßarrs either in the basal state, activated by the muscarinic receptor subtype 2 (M2R) through its third intracellular loop, or activated by the ßarr-biased decoy D6 receptor (D6R). Combined with biochemical, cellular, and biophysical experiments, these structural snapshots allow the visualization of atypical engagement of ßarrs with 7TMRs and also reveal a structural transition in the carboxyl terminus of ßarr2 from a ß strand to an α helix upon activation by D6R. Our study provides previously unanticipated molecular insights into the structural and functional diversity encoded in 7TMR-ßarr complexes with direct implications for exploring novel therapeutic avenues.

Nasal Masses: A Report of Two Rare Cases, from Benign to Malignant.

Medical practitioners in peripheral remote areas face challenges in treating patients, that are much different from those who are working in an institute or accessible regions. We are discussing two cases, which were clinically diagnosed at our centre and were biopsy proven at a tertiary care institute. First case is of a benign adnexal neoplasm while the second is dreaded midline granuloma. Both the patients received satisfactory consultation and management.

Molecular basis of anaphylatoxin binding, activation, and signaling bias at complement receptors.

The complement system is a critical part of our innate immune response, and the terminal products of this cascade, anaphylatoxins C3a and C5a, exert their physiological and pathophysiological responses primarily via two GPCRs, C3aR and C5aR1. However, the molecular mechanism of ligand recognition, activation, and signaling bias of these receptors remains mostly elusive. Here, we present nine cryo-EM structures of C3aR and C5aR1 activated by their natural and synthetic agonists, which reveal distinct binding pocket topologies of complement anaphylatoxins and provide key insights into receptor activation and transducer coupling. We also uncover the structural basis of a naturally occurring mechanism to dampen the inflammatory response of C5a via proteolytic cleavage of the terminal arginine and the G-protein signaling bias elicited by a peptide agonist of C3aR identified here. In summary, our study elucidates the innerworkings of the complement anaphylatoxin receptors and should facilitate structure-guided drug discovery to target these receptors in a spectrum of disorders.

Prevalence and antibiogram of bacteria causing urinary tract infection among patients with chronic kidney disease.

Identifying and appropriately managing urinary tract infections (UTIs) among chronic kidney disease (CKD) patients are essential to reduce further disease complications and economic burden. Hence, this study aims to determine the prevalence of UTIs among CKD patients and study the antibiogram of the bacterial isolates. Four hundred eighty-two clean catch midstream urine samples were collected from CKD patients during the study period. The samples were cultured, and bacteria were isolated using standard microbiological techniques. Antibiotic susceptibility testing was performed by the Kirby-Bauer disc diffusion method following the Clinical and Laboratory Standards Institute guidelines. Of the 482 CKD patients, 15.8% were culture positive, and the majority was elderly aged group population. Most bacterial isolates were Escherichia coli 50%, followed by Pseudomonas aeruginosa 15.80%, Enterococcus species 15.80%, and Klebsiella pneumoniae 11.84%. The majority of bacteria were found to be resistant to beta-lactam antibiotics, ampicillin (94.67%), ceftriaxone (89.04%), cefotaxime (87.5%), and ceftazidime (84.0%), while polymyxin, colistin, vancomycin, meropenem, and imipenem were the most sensitive antibiotics. In our study, higher levels of antibiotic resistance were observed among urinary isolates. Therefore, our findings suggest clinicians to choose better antibiotic options to treat UTIs among CKD patients.

Stunting in infancy is associated with atypical activation of working memory and attention networks.

Stunting is associated with poor long-term cognitive, academic and economic outcomes, yet the mechanisms through which stunting impacts cognition in early development remain unknown. In a first-ever neuroimaging study conducted on infants from rural India, we demonstrate that stunting impacts a critical, early-developing cognitive system-visual working memory. Stunted infants showed poor visual working memory performance and were easily distractible. Poor performance was associated with reduced engagement of the left anterior intraparietal sulcus, a region involved in visual working memory maintenance and greater suppression in the right temporoparietal junction, a region involved in attentional shifting. When assessed one year later, stunted infants had lower problem-solving scores, while infants of normal height with greater left anterior intraparietal sulcus activation showed higher problem-solving scores. Finally, short-for-age infants with poor physical growth indices but good visual working memory performance showed more positive outcomes suggesting that intervention efforts should focus on improving working memory and reducing distractibility in infancy.

Indigenous chicken production system in different agro-ecology of Indian Himalayan Region: implication on food and economic security.

The indigenous chicken production system (ICPS) has several use values and ecosystem services. In the last few years, ICPS has been recognized for its possible contribution to household food security, income generation, wildlife protection, and bettering the women's lives. This study aimed to collect, for the first time, comprehensive information about ICPS in three different agro-ecologies (tropical, sub-tropical, and sub-temperate) of the Indian Himalayan Region (IHR) and its role in food and economic security of traditional communities. In this study region, ICPS is semi-extensive, providing homegrown feed and temporary night shelter. In sub-temperate agro-ecology, females owned non-significant (p = 0.170) more indigenous chicken flocks than males. Households in sub-temperate agro-ecologies had significantly (p ≤ 0.001) larger flock sizes and tropical livestock units (chicken-TLU). However, the livestock diversity index (LDI) was significantly higher (p ≤ 0.001) in tropical and subtropical agro-ecology. The households in the sub-temperate region highly (p ≤ 0.001) valued indigenous chicken because of its survivability and adaptability. In absolute numbers significant (p ≤ 0.001) higher numbers of adult birds died in past 1 year in sub-temperate agro-ecology. The mortality rate of adult birds in sub-temperate agro-ecology was 9%, and it was 14 and 15% in tropical and sub-tropical agro-ecologies, respectively. In sub-temperate agro-ecology, larger flock size translated into significantly higher (p ≤ 0.001) egg production and subsequently a significant (p ≤ 0.001) higher egg consumption per household per month. In sub-temperate agro-ecology, households' dietary diversity score was significantly (p ≤ 0.001) higher. Similarly, the average annual income from ICPS was significantly higher (p ≤ 0.001) in sub-temperate agro-ecology and accounted for 18% of household income. ICPS' marketing chain was relatively short in the sub-temperate region. In all agro-ecologies, indigenous chicken and egg demand was significantly higher (p ≤ 0.001) in the winter. ICPS litter is used as farmyard manure, enhancing ecological resilience. In all agro-ecologies, the three most frequently cited obstacles to extending the indigenous chicken production system are illnesses, predators, and a lack of chicks availability. ICPS contributes to food and nutritional security, economic stability, and ecological resilience in this hilly and fragile ecosystem. Even though the system is self-sustaining, management and health interventions can increase production and productivity.

Unveiling the microbial diversity and functional dynamics of Shiv Kund, Sohna hot spring, India through a shotgun metagenomics approach.

In this research, we examined the microbial diversity in Sohna hot spring, Haryana, India using shotgun metagenome sequencing based on the Illumina Hiseq 4000 sequencing technology. The raw sequence data from metagenomic paired-end libraries were analysed for taxonomic classification, diversity, and functional annotation using MG-RAST online server. The results showed the presence of total of 57 phyla, 931 genera, and 2068 species, predominantly occupied by Moraxellaceae (Gammaproteobacteria). However, at the species level, we reported the presence of some representative pathogenic taxa, such as Acinetobacter baumannii and Moraxella osloensis. The functional annotation predicted at various levels based on SEED-based subsystem, KEGG ortholog identity (KO), Cluster of Orthologous Groups (COGs) database identified the predominance of genes associated with primary and secondary metabolism along with a crucial role in environmental and genetic signals, cellular communication, and cell signalling. Comparative Genome Analysis (CGA) using The Pathosystem Resource Integration Centre (PATRIC) tool based on genome annotation and assembly of the metagenomic libraries for representative taxon Acinetobacter baumannii (NCBI tax id:470) characterized the reads with a unique genome identifier of 470.20380 (A. baumannii DDLJ4) which is evolutionary closer to A. baumannii ATCC 470.17978 400667.7. In addition, the CARD database results about the presence of potential AMR pathotypes and the prevalence of adeABC, adeIJK, abeM gene-specific clusters that function as multidrug efflux pumps. Overall, the results provided a comprehensive insight into virulence and anti-microbial resistance mechanism and could be useful for developing potential drug targets against the possible AMR pathotypes.

Pseudoaneurysm: Cause of Unusual Postoperative Bleed in Head and Neck.

Although, instances of postoperative bleeding in ENT surgery are infrequent, sometimes they can be dreadful for both patient & surgeon. Here we are reporting 2 cases of postoperative bleeding that we encountered recently. (1) Superficial temporal artery aneurysmal bleed- post parotidectomy (2) Left superior thyroid artery aneurysmal bleed- post tracheostomy.

Recent Developments and Future Perspectives of Vaccines and Therapeutic Agents against SARS-CoV2 Using the BCOV_S1_CTD of the S Protein.

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the virus kept developing and mutating into different variants over time, which also gained increased transmissibility and spread in populations at a higher pace, culminating in successive waves of COVID-19 cases. The scientific community has developed vaccines and antiviral agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease. Realizing that growing SARS-CoV-2 variations significantly impact the efficacy of antiviral therapies and vaccines, we summarize the appearance and attributes of SARS-CoV-2 variants for future perspectives in drug design, providing up-to-date insights for developing therapeutic agents targeting the variants. The Omicron variant is among the most mutated form; its strong transmissibility and immune resistance capacity have prompted international worry. Most mutation sites currently being studied are in the BCOV_S1_CTD of the S protein. Despite this, several hurdles remain, such as developing vaccination and pharmacological treatment efficacies for emerging mutants of SARS-CoV-2 strains. In this review, we present an updated viewpoint on the current issues faced by the emergence of various SARS-CoV-2 variants. Furthermore, we discuss the clinical studies conducted to assist the development and dissemination of vaccines, small molecule therapeutics, and therapeutic antibodies having broad-spectrum action against SARS-CoV-2 strains.

Evolutionary aspects of mutation in functional motif and post-translational modifications in SARS-CoV-2 3CLpro (Mpro): an in-silico study.

SARS CoV-2 is the virus that caused the COVID-19 pandemic. The main protease is one of the most prominent pharmacological targets for developing anti-COVID-19 therapeutic drugs (Mpro); SARS-CoV-2 replication is dependent on this component. SARS CoV-2's Mpro/cysteine protease is quite identical to SARS CoV-1's Mpro/cysteine protease. However, there is limited information on its structural and conformational properties. The present study aims to perform a complete in silico evaluation of Mpro protein's physicochemical properties. The motif prediction, post-translational modifications, effect of point mutation, and phylogenetic links were studied with other homologs to understand the molecular and evolutionary mechanisms of these proteins. The Mpro protein sequence was obtained in FASTA format from the RCSB Protein Data Bank. The structure of this protein was further characterized and analyzed using standard bioinformatics methods. According to Mpro's in-silico characterization, the protein is a basic, non-polar, and thermally stable globular protein. The outcomes of the phylogenetic and synteny study showed that the protein's functional domain amino acid sequence is substantially conserved. Furthermore, it has undergone many changes at the motif level over time from porcine epidemic diarrhoea virus to SARS-CoV 2, possibly to achieve various functions. Several post-translational modifications (PTMs) were also observed, and the possibilities of changes in Mpro protein exhibit additional orders of peptidase function regulation. During heatmap development, the effect of a point mutation on the Mpro protein was seen. This protein's structural characterization will aid in a better understanding of its function and mechanism of action. Supplementary Information: The online version contains supplementary material available at 10.1007/s42485-023-00105-9.

Empirical Data Suggest That the Kashmir Musk Deer (Moschus cupreus, Grubb 1982) Is the One Musk Deer Distributed in the Western Himalayas: An Integration of Ecology, Genetics and Geospatial Modelling Approaches.

Insufficient research has been conducted on musk deer species across their distribution range, primarily because of their elusive behaviour and the fact they occupy remote high-altitude habitats in the Himalayas above 2500 m. The available distribution records, primarily derived from ecological studies with limited photographic and indirect evidence, fail to provide comprehensive information on the species distribution. Consequently, uncertainties arise when attempting to determine the presence of specific taxonomic units of musk deer in the Western Himalayas. This lack of knowledge hampers species-oriented conservation efforts, as there need to be more species-specific initiatives focused on monitoring, protecting, and combatting the illegal poaching of musk deer for their valuable musk pods. We used transect surveys (220 trails), camera traps (255 cameras), non-invasive DNA sampling (40 samples), and geospatial modelling (279 occurrence records) to resolve the taxonomic ambiguity, and identify the suitable habitat of musk deer (Moschus spp.) in Uttarkashi District of Uttarakhand and the Lahaul-Pangi landscape of Himachal Pradesh. All the captured images and DNA-based identification results confirmed the presence of only Kashmir musk deer (KDM) (Moschus cupreus) in Uttarakhand and Himachal Pradesh. The results suggest that KMD inhabit a narrow range of suitable habitats (6.9%) of the entire Western Himalayas. Since all evidence indicates that only KMD are present in the Western Himalayas, we suggest that the presence of other species of musk deer (Alpine musk deer and Himalayan musk deer) was wrongly reported. Therefore, future conservation plans and management strategies must focus only on KMD in the Western Himalayas.

Phase 2 randomised placebo-controlled trial of spironolactone and dexamethasone versus dexamethasone in COVID-19 hospitalised patients in Delhi.

BACKGROUND: In this phase 2 randomised placebo-controlled clinical trial in patients with COVID-19, we hypothesised that blocking mineralocorticoid receptors using a combination of dexamethasone to suppress cortisol secretion and spironolactone is safe and may reduce illness severity. METHODS: Hospitalised patients with confirmed COVID-19 were randomly allocated to low dose oral spironolactone (50 mg day 1, then 25 mg once daily for 21 days) or standard of care in a 2:1 ratio. Both groups received dexamethasone 6 mg daily for 10 days. Group allocation was blinded to the patient and research team. Primary outcomes were time to recovery, defined as the number of days until patients achieved WHO Ordinal Scale (OS) category ≤ 3, and the effect of spironolactone on aldosterone, D-dimer, angiotensin II and Von Willebrand Factor (VWF). RESULTS: One hundred twenty patients with PCR confirmed COVID were recruited in Delhi from 01 February to 30 April 2021. 74 were randomly assigned to spironolactone and dexamethasone (SpiroDex), and 46 to dexamethasone alone (Dex). There was no significant difference in the time to recovery between SpiroDex and Dex groups (SpiroDex median 4.5 days, Dex median 5.5 days, p = 0.055). SpiroDex patients had significantly lower D-dimer levels on days 4 and 7 (day 7 mean D-dimer: SpiroDex 1.15 µg/mL, Dex 3.15 µg/mL, p = 0.0004) and aldosterone at day 7 (SpiroDex 6.8 ng/dL, Dex 14.52 ng/dL, p = 0.0075). There was no difference in VWF or angiotensin II levels between groups. For secondary outcomes, SpiroDex patients had a significantly greater number of oxygen free days and reached oxygen freedom sooner than the Dex group. Cough scores were no different during the acute illness, however the SpiroDex group had lower scores at day 28. There was no difference in corticosteroid levels between groups. There was no increase in adverse events in patients receiving SpiroDex. CONCLUSION: Low dose oral spironolactone in addition to dexamethasone was safe and reduced D-dimer and aldosterone. Time to recovery was not significantly reduced. Phase 3 randomised controlled trials with spironolactone and dexamethasone should be considered. TRIAL REGISTRATION: The trial was registered on the Clinical Trials Registry of India TRI: CTRI/2021/03/031721, reference: REF/2021/03/041472. Registered on 04/03/2021.