The inflammatory response is a highly regulated process, and its dysregulation can lead to the establishment of chronic inflammation and, in some cases, to death. Inflammation is the cause of several diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and asthma. The search for agents inhibiting inflammation is a great challenge as the inflammatory response plays an important role in the defense of the host to infections. Marine invertebrates are exceptional sources of new natural products, and among those diterpenoids secondary metabolites exhibit notable anti-inflammatory properties. Novel anti-inflammatory diterpenoids, exclusively produced by marine organisms, have been identified and synthetic molecules based on those structures have been obtained. The anti-inflammatory activity of marine diterpenoids has been attributed to the inhibition of Nuclear Factor-κB activation and to the modulation of arachidonic acid metabolism. However, more research is necessary to describe the mechanisms of action of these secondary metabolites. This review is a compilation of marine diterpenoids, mainly isolated from corals, which have been described as potential anti-inflammatory molecules.

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Marine Diterpenoids as Potential Anti-Inflammatory Agents

Despite intense research efforts towards clinical and molecular causes of Parkinson disease (PD), the etiology of disease still remains unclear. However, recent studies have provided ample evidences that the oxidative stress is the key player that contributes a lot to dopaminergic (DAergic) neurodegeneration in brain. It is due to the discrepancy of antioxidant defence system of which nuclear factor erythroid 2-related factor 2 (Nrf2) signalling is of central contour. In the current study, potent heme oxygenase-1 agonists (Nrf2 signalling regulator), vinyl sulfones, were selected and an optimal pharmacophore model was brought forth which was examined using a decoy set by atom-based 3D-QSAR. The best four-feature model consists of two hydrogen bond acceptors and two aromatic rings, which has the highest correlation coefficient, R(2) = .71 and [Formula: see text] = .73 in QSAR. These ligands were further studied for molecular docking with Nrf2-keap protein to gain insight into the major binding motifs followed by analysing pharmacokinetic properties to evaluate their bioavailability dominance. From this study, it is concluded that vinyl sulfones could be ideal compounds for targeting Nrf2 pathway which in turn halt the PD progression. Hence, these can be considered as potential leads for drug development against the same.

Pharmacophore model prediction, 3D-QSAR and molecular docking studies on vinyl sulfones targeting Nrf2-mediated gene transcription intended for anti-Parkinson drug design

Meridianin derivatives as potent Dyrk1A inhibitors and neuroprotective agents.

The structures, names, bioactivities, and references of 124 briarane-type natural products, including 66 new metabolites, isolated between 2014 and 2016 are summarized in this review article. All of the briarane diterpenoids mentioned in this review were isolated from octocorals, mainly from Briareum violacea, Dichotella gemmacea, Ellisella dollfusi, Junceella fragilis, Junceella gemmacea, and Pennatula aculeata. Some of these compounds exhibited potential biomedical activities, including anti-inflammatory activity, antibacterial activity, and cytotoxicity towards cancer cells.

Briarane Diterpenoids Isolated from Octocorals between 2014 and 2016.

Ligand-based pharmacophore filtering, atom based 3D-QSAR, virtual screening and ADME studies for the discovery of potential ck2 inhibitors

A new briarane-type diterpenoid, named 2-acetoxyverecynarmin C, was isolated from the methanolic extract of an octocoral, Pennatula aculeata, that exhibited cyclooxygenase (COX) inhibitory activity. The structure of the compound was elucidated by ESI-HRMS, 1D and 2D NMR spectroscopy and comparison of the measured spectral data with those reported in the literature. The relative stereochemistry at chiral carbons was established from 2D NOESY experiments. 2-Acetoxyverecynarmin C is a tricyclic compound containing a furan ring at C-7,8 of a briarane skeleton. 2-Acetoxyverecynarmin C showed moderate inhibitory activity in in vitro COX-1 and COX-2 assays.

https://journals.sagepub.com/doi/pdf/10.1177/1934578X1400900820

2-Acetoxyverecynarmin C, a new briarane COX inhibitory diterpenoid from Pennatula aculeata.

Dyrk family enzymes are essential components of important signaling casades in the pathophysiology of cancer and Alzheimer’s disease. Especially, Dyrk2 biological expression levels regulate key signaling processes in these diseases. In the present work, a pharmacophore-based 3D-QSAR model was generated for a series of leucettine analogs possessing Dyrk2 inhibitory activity. Developed pharmacophore model contains four hydrogen bond acceptors (A) and one hydrophobic aromatic ring (R). These are crucial molecular fingerprints which predict binding efficacy of high affinity and low affinity ligands to the Dyrk2 enzyme. These pharmacophoric features point toward key structural requirements of leucettines for potent Dyrk2 inhibition. Furthermore, a biological correlation between pharmacophore hypothesis-based 3D-QSAR variables and functional fingerprints of leucettines responsible for the receptor binding was observed. Alignment of the developed model with Dyrk2 crystal structure indicated importance of A3 and A4 H-bond accetor sites, which are involved in the important interactions with Leu231A and Lys178A residues of the active site. Excellent statistical results of QSAR model such as good correlation coefficient (r
 2 > 0.95), higher F value (F > 106), and excellent predictive power (Q
 2 > 0.7) with low standard deviation (SD < 0.2) strongly suggest that the developed model is good for the future prediction of Dyrk2 inhibitory activity of new leucettine analogs.

Pharmacophore modeling and 3D-QSAR studies of leucettines as potent Dyrk2 inhibitors

Pharmacophore Based 3D-QSAR Modeling and Molecular Docking of Leucettines as Potent Dyrk1A Inhibitors

Data comparing the clinical spectrum of COVID-19 in kidney transplant recipients (KTRs) during the first and second waves of the pandemic in India is limited. Our single-center retrospective study compared the clinical profile, mortality, and associated risk factors in KTRs with COVID-19 during the 1st wave (1st February 2020 to 31st January 2021) and the second wave (1st March-31st August 2021). 156 KTRs with PCR confirmed SARS-CoV-2 infection treated at a tertiary care hospital in New Delhi during the 1st and the second waves were analyzed. The demographics and baseline transplant characteristics of the patients diagnosed during both waves were comparable. Patients in the second wave reported less frequent hospitalization, though the intensive care unit (ICU) and ventilator requirements were similar. Strategies to modify immunosuppressants such as discontinuation of antinucleoside drugs with or without change in calcineurin inhibitors and the use of steroids were similar during both waves. Overall patient mortality was 27.5%. The demographics and baseline characteristics of survivors and nonsurvivors were comparable. A higher percentage of nonsurvivors presented with breathing difficulty, low SpO2, and altered sensorium. Both wave risk factors for mortality included older age, severe disease, ICU/ventilator requirements, acute kidney injury (AKI) needing dialysis, Chest Computerized Tomographic (CT) scan abnormalities, and higher levels of inflammatory markers particularly D-dimer and interleukin-6 levels. Conclusions. KTRs in both COVID-19 waves had similar demographics and baseline characteristics, while fewer patients during the second wave required hospitalization. The D-dimer and IL-6 levels are directly correlated with mortality.

A Comprehensive Comparison of Clinical Presentation and Outcomes of Kidney Transplant Recipients with COVID-19 during Wave 1 versus Wave 2 at a Tertiary Care Center, India

ABSTRACT Background To investigate the anti-spike antibody response to vaccination in kidney transplant recipients (KTRs) previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as compared with KTRs with no history of coronavirus disease 2019 (COVID-19) from India. Methods SARS-CoV-2 spike immunoglobulin (Ig) G antibody response was measured in 105 post-COVID-19 KTRs with PCR-confirmed SARS-CoV-2 infection who received either no vaccination (cohort 1), a single dose (cohort 2) or two doses (cohort 3) of vaccine and compared with 103 two-dose vaccinated COVID-19-naïve KTRs with no history of COVID-19 (cohort 4). Results Out of 103 COVID-19-naïve two-dose vaccinated KTRs, <50% became seropositive with anti-spike antibody titres >50 arbitrary unit/mL subsequent to complete vaccination, the seroconversion rate being comparable in subjects receiving CovishieldTM versus CovaxinTM vaccines. However, the seropositive KTRs vaccinated with CovishieldTM had higher anti-spike antibody titres as compared with those who received CovaxinTM. We observed higher anti-SARS-CoV-2 spike antibody levels in post-COVID-19 KTRs after one dose of vaccine as compared with COVID-19-naïve two-dose vaccinated KTRs. Importantly, the second dose in post-COVID-19 KTRs did not significantly increase anti-spike antibody levels compared with the single-dose recipients. Conclusions Our data present that in KTRs with previous SARS-CoV-2 infection, a single dose of vaccine (CovishieldTM) may be effective in mounting an optimal immune response. In contrast, COVID-19-naïve two-dose vaccinated KTRs respond poorly (<50%) to the current recommendation of a two-dose regimen in India.

Post-vaccination analysis of anti-spike antibody responses in kidney transplant recipients with and without COVID-19 infection in a tertiary care centre, India

Anu Bahl

Papers

2-Acetoxyverecynarmin C, a new briarane COX inhibitory diterpenoid from Pennatula aculeata.

Pharmacophore modeling and 3D-QSAR studies of leucettines as potent Dyrk2 inhibitors

Pharmacophore Based 3D-QSAR Modeling and Molecular Docking of Leucettines as Potent Dyrk1A Inhibitors

A Comprehensive Comparison of Clinical Presentation and Outcomes of Kidney Transplant Recipients with COVID-19 during Wave 1 versus Wave 2 at a Tertiary Care Center, India

Post-vaccination analysis of anti-spike antibody responses in kidney transplant recipients with and without COVID-19 infection in a tertiary care centre, India