Publications by authors named "Manish K Jain"

Article Synopsis
  • This study aimed to assess whether DMX-200, a chemokine receptor antagonist, combined with candesartan, could improve outcomes for hospitalized adults under 65 with moderate to severe COVID-19.
  • Conducted in ten hospitals in India, the trial was double-blind and placebo-controlled but was terminated early due to challenges in recruitment, resulting in only 49 participants.
  • Preliminary results showed both treatment groups had similar outcomes, with no significant differences in disease progression, ICU admissions, or length of hospital stays, indicating that the intervention may not have had a notable impact.
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  • AlphaFold2 (AF2) models show promise in drug discovery for ligands but have variable performance when retrospectively tested.
  • In a study, researchers docked large libraries of new molecules against AF2 models of σ and serotonin 2A receptors, finding similar hit rates and affinities to those obtained from experimental structures.
  • Cryo-electron microscopy confirmed that AF2-model predictions were relevant, suggesting that AF2 models can find low-energy conformations important for ligand discovery, even if they differ from experimental structures.
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  • Bitter taste sensing involves type 2 taste receptors (TAS2Rs), specifically TAS2R14, which responds to a wide range of bitter compounds and is highly expressed in tissues outside the mouth.
  • Researchers used cryo-electron microscopy to identify two specific structures of TAS2R14 in complex with proteins gustducin (G) and G, revealing key binding sites for cholesterol and the bitter tastant cmpd28.1.
  • The study suggests that cholesterol acts as an agonist while cmpd28.1 serves as a positive allosteric modulator, indicating that TAS2R14 has functions that extend beyond just sensing bitter tastes.
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Introduction: Once-daily inhalers have been shown to improve adherence leading to lesser discontinuation compared to twice- or thrice-daily inhalers in management of asthma. Combination of Vilanterol and Fluticasone Furoate (VI/FF) is approved for management of asthma and COPD and is available as a dry powder inhaler. Pressurized-Metered Dose Inhalers (pMDIs) offer ease-of-use and therapy alternatives for patients with low inspiratory flow.

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AlphaFold2 (AF2) and RosettaFold have greatly expanded the number of structures available for structure-based ligand discovery, even though retrospective studies have cast doubt on their direct usefulness for that goal. Here, we tested unrefined AF2 models , comparing experimental hit-rates and affinities from large library docking against AF2 models vs the same screens targeting experimental structures of the same receptors. In docking screens against the σ and the 5-HT2A receptors, the AF2 structures struggled to recapitulate ligands that we had previously found docking against the receptors' experimental structures, consistent with published results.

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One of the most preferable characteristics for a COVID-19 vaccine candidate is the ability to reduce transmission and infection of SARS-CoV-2, in addition to disease prevention. Unlike intramuscular vaccines, intranasal COVID-19 vaccines may offer this by generating mucosal immunity. In this open-label, randomised, multicentre, phase 3 clinical trial (CTRI/2022/02/40065; ClinicalTrials.

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Human α-, β-, and γ-synuclein (syn) are natively unfolded proteins present in the brain. Deposition of aggregated α-syn in Lewy bodies is associated with Parkinson's disease (PD) and γ-syn is known to be involved in both neurodegeneration and breast cancer. At physiological pH, while α-syn has the highest propensity for fibrillation followed by γ-syn, β-syn does not form any fibrils.

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Opioids are effective analgesics, but their use is beset by serious side effects, including addiction and respiratory depression, which contribute to the ongoing opioid crisis. The human opioid system contains four opioid receptors (μOR, δOR, κOR, and NOPR) and a set of related endogenous opioid peptides (EOPs), which show distinct selectivity toward their respective opioid receptors (ORs). Despite being key to the development of safer analgesics, the mechanisms of molecular recognition and selectivity of EOPs to ORs remain unclear.

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Background: The safety and efficacy of fixed-dose combination (FDC) of glycopyrronium bromide 12.5 μg/formoterol fumarate 12 μg (GB/FF) twice daily as dry powder inhalers (DPIs) compared to glycopyrronium 50 μg monotherapy (GLY) once daily as DPI in subjects with moderate-to-severe chronic obstructive pulmonary disease (COPD) were evaluated.

Methods: This was a phase-3, randomized, double-blind, active-controlled, parallel-group, superiority study conducted in India.

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Background At the peak of the coronavirus disease 2019 (COVID-19) pandemic, the need for an orally administered agent to prevent the progression of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection became increasingly evident, which was the impetus behind our investigations with molnupiravir. Molnupiravir has been shown to be effective in preventing hospitalizations and/or clinical complications in patients with mild-to-moderate COVID-19. In this study, we evaluate the efficacy and safety of molnupiravir in Indian patients with mild SARS-CoV-2 infection and at least one risk factor for disease progression (CTRI/2021/05/033739).

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Serotonin (5-hydroxytryptamine; 5-HT) 2A receptor (5-HT2AR) signaling is essential for the actions of classical psychedelic drugs. In this study, we examined whether sequence variations in the 5-HT2AR gene affect the signaling of four commonly used psychedelic drugs. We examined the pharmacology of seven non-synonymous single-nucleotide polymorphisms (SNPs), which give rise to Ser12Asn, Thr25Asn, Asp48Asn, Ile197Val, Ala230Thr, Ala447Val, and His452Tyr variant 5-HT2A serotonin receptors.

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An array of triazolopyridines based on JNJ-46356479 () were synthesized as potential positron emission tomography radiotracers for metabotropic glutamate receptor 2 (mGluR2). The selected candidates featured enhanced positive allosteric modulator (PAM) activity (20-fold max.) and mGluR2 agonist activity (25-fold max.

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Objective: To compare the efficacy and safety of a fixed dose combination of Fluticasone Furoate and Oxymetazoline Hydrochloride Nasal Spray 27.5/50 mcg (FDC) with Fluticasone Furoate Nasal Spray 27.5 mcg (Fluticasone) in the management of allergic rhinitis.

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Metabotropic glutamate receptor 2 (mGluR2) is a therapeutic target for several neuropsychiatric disorders. An mGluR2 function in etiology could be unveiled by positron emission tomography (PET). In this regard, 5-(2-fluoro-4-[C]methoxyphenyl)-2,2-dimethyl-3,4-dihydro-2-pyrano[2,3-]pyridine-7-carboxamide ([C], [C]mG2N001), a potent negative allosteric modulator (NAM), was developed to support this endeavor.

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Structure-based virtual ligand screening is emerging as a key paradigm for early drug discovery owing to the availability of high-resolution target structures and ultra-large libraries of virtual compounds. However, to keep pace with the rapid growth of virtual libraries, such as readily available for synthesis (REAL) combinatorial libraries, new approaches to compound screening are needed. Here we introduce a modular synthon-based approach-V-SYNTHES-to perform hierarchical structure-based screening of a REAL Space library of more than 11 billion compounds.

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Women spend relatively more time in indoor environments in developing countries. Exposure to various indoor air pollutants leads them to higher health risks according to household air quality in which they reside. Particulate matter (PM) exposure with their exposure duration inside the household plays a significant role in women's respiratory problems.

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Background: The rise in particulate matter (PM) concentrations is a serious problem for the environment. Heavy metals associated with PM, PM, and road dust adversely affect human health. Different methods have been used to assess heavy metal contamination in PM, PM, and road dust and source apportionment of these heavy metals.

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Jharia Coalfield (JCF) is one of the oldest coalfields in the eastern part of India and falls under critically polluted areas as per CPCB/MoEFCC Notification. Therefore, a study of air pollution and its management is the demand of the day. This study had been undertaken to know the current status of JCF concerning air quality.

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Extensive measurements of equivalent black carbon (EBC) aerosol mass concentration at fifteen stations of India Meteorological Department (IMD) BC observation network during the period 2016-2018 are used to study the spatial and temporal heterogeneity over India. The sampling sites represent different geographical region of India. Spatial distribution shows higher values of EBC over stations of north India and IGP.

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In recent years, the application of biochar has increased significantly for sustainable and efficient carbon sequestration, improving soil quality and enhancement of plant growth. The biochar is mostly made from agricultural residues and waste materials. The objective of this study was to assess the changes in physicochemical, surface morphology, and mineral composition of different biochars with varying pyrolysis temperature.

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The degradation of land by trace metals contamination around coal mining areas is a serious environmental issue, and therefore, it is necessary to have detailed information about the pollution caused by them and their sources. The objective of the work was to study the impact of trace metals (e.g.

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The dopamine D1 receptor (D1R) is essential for neurotransmission in various brain pathways where it modulates key functions including voluntary movement, memory, attention and reward. Not surprisingly, the D1R has been validated as a promising drug target for over 40 years and selective activation of this receptor may provide novel neurotherapeutics for neurodegenerative and neuropsychiatric disorders. Several pharmacokinetic challenges with previously identified small molecule D1R agonists have been recently overcome with the discovery and advancement of new ligands, including drug-like non-catechol D1R agonists and positive allosteric modulators.

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The human synuclein (syn) family is comprised of α-, β-, and γ-syn proteins. α-syn has the highest propensity for aggregation, and its aggregated forms accumulate in Lewy bodies (LB) and Lewy neurites, which are involved in Parkinson's disease (PD). β- and γ-syn are absent in LB, and their exact role is still enigmatic.

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Accumulating evidence suggests that deposition of neurotoxic α-synuclein aggregates in the brain during the development of neurodegenerative diseases like Parkinson's disease can be curbed by anti-aggregation strategies that either disrupt or eliminate toxic aggregates. Curcumin, a dietary polyphenol exhibits anti-amyloid activity but the use of this polyphenol is limited owing to its instability. As chemical modifications in curcumin confiscate this limitation, such efforts are intensively performed to discover molecules with similar but enhanced stability and superior properties.

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