cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.28652171
title: Bigger.srt

description: Timestamps and transcription for public speaking: "Bigger"
DOI: 10.6084/m9.figshare.24961533.v1
title: Inhibitory potential of furanocoumarins against cyclin dependent kinase 4 using integrated docking, molecular dynamics and ONIOM methods

description: Cyclin Dependent Kinase 4 (CDK4) is vital in the process of cell-cycle and serves as a G1 phase checkpoint in cell division. Selective antagonists of CDK4 which are in use as clinical chemotherapeutics cause various side-effects in patients. Furanocoumarins induce anti-cancerous effects in a range of human tumours. Therefore, targeting these compounds against CDK4 is anticipated to enhance therapeutic effectiveness. This work intended to explore the CDK4 inhibitory potential of 50 furanocoumarin molecules, using a comprehensive approach that integrates the processes of docking, drug-likeness, pharmacokinetic analysis, molecular dynamics simulations and ONIOM (Our own N-layered Integrated molecular Orbital and Molecular mechanics) methods. The top five best docked compounds obtained from docking studies were screened for subsequent analysis. The molecules displayed good pharmacokinetic properties and no toxicity. Epoxybergamottin, dihydroxybergamottin and notopterol were found to inhabit the ATP-binding zone of CDK4 with substantial stability and negative binding free energy forming hydrogen bonds with key catalytic residues of the protein. Notopterol exhibiting the highest binding energy was subjected to ONIOM calculations wherein the hydrogen bonding interactions were retained with significant negative interaction energy. Hence, through these series of computerised methods, notopterol was screened as a potent CDK4 inhibitor and can act as a starting point in successive processes of drug design.
DOI: 10.6084/m9.figshare.24961533
title: Inhibitory potential of furanocoumarins against cyclin dependent kinase 4 using integrated docking, molecular dynamics and ONIOM methods

description: Cyclin Dependent Kinase 4 (CDK4) is vital in the process of cell-cycle and serves as a G1 phase checkpoint in cell division. Selective antagonists of CDK4 which are in use as clinical chemotherapeutics cause various side-effects in patients. Furanocoumarins induce anti-cancerous effects in a range of human tumours. Therefore, targeting these compounds against CDK4 is anticipated to enhance therapeutic effectiveness. This work intended to explore the CDK4 inhibitory potential of 50 furanocoumarin molecules, using a comprehensive approach that integrates the processes of docking, drug-likeness, pharmacokinetic analysis, molecular dynamics simulations and ONIOM (Our own N-layered Integrated molecular Orbital and Molecular mechanics) methods. The top five best docked compounds obtained from docking studies were screened for subsequent analysis. The molecules displayed good pharmacokinetic properties and no toxicity. Epoxybergamottin, dihydroxybergamottin and notopterol were found to inhabit the ATP-binding zone of CDK4 with substantial stability and negative binding free energy forming hydrogen bonds with key catalytic residues of the protein. Notopterol exhibiting the highest binding energy was subjected to ONIOM calculations wherein the hydrogen bonding interactions were retained with significant negative interaction energy. Hence, through these series of computerised methods, notopterol was screened as a potent CDK4 inhibitor and can act as a starting point in successive processes of drug design.
DOI: 10.6084/m9.figshare.28533756
title: Molluscan microbiomes: current research focus, knowledge gaps, and future directions

description: Microbiome research has increased exponentially in recent years. This is not different for molluscs. We now know that molluscan-associated microbes are involved in the most diverse roles, from aiding digestion to the production of light. However, impacts of the microbiome on molluscan ecology and evolution are still poorly understood. Here, we present a systematic review of the literature on molluscan microbiomes, aiming to portray the current state of the field and with no pretension to summarise all the knowledge on molluscan microbiomes. Based on our review, we identified knowledge gaps and opportunities for future research. We have found that gastropods and bivalves are the most researched classes, and the gut is the most used tissue for microbiome assessments in molluscs. While studies focusing on microbiome characterisations are extremely common, a widespread concern among malacologists is microbiome responses to anthropogenic pressure. We propose that diversifying the molluscan groups assessed and tissues used will be important to address gaps in knowledge. At the same time, partnership with the aquaculture sector and greater use of the ‘omics toolbox’ are promising avenues for a more thorough understanding of molluscs as holobionts.
DOI: 10.6084/m9.figshare.28533756.v1
title: Molluscan microbiomes: current research focus, knowledge gaps, and future directions

description: Microbiome research has increased exponentially in recent years. This is not different for molluscs. We now know that molluscan-associated microbes are involved in the most diverse roles, from aiding digestion to the production of light. However, impacts of the microbiome on molluscan ecology and evolution are still poorly understood. Here, we present a systematic review of the literature on molluscan microbiomes, aiming to portray the current state of the field and with no pretension to summarise all the knowledge on molluscan microbiomes. Based on our review, we identified knowledge gaps and opportunities for future research. We have found that gastropods and bivalves are the most researched classes, and the gut is the most used tissue for microbiome assessments in molluscs. While studies focusing on microbiome characterisations are extremely common, a widespread concern among malacologists is microbiome responses to anthropogenic pressure. We propose that diversifying the molluscan groups assessed and tissues used will be important to address gaps in knowledge. At the same time, partnership with the aquaculture sector and greater use of the ‘omics toolbox’ are promising avenues for a more thorough understanding of molluscs as holobionts.
DOI: 10.6084/m9.figshare.24961480
title: Bitter taste receptors establish a stable binding affinity with the SARS-CoV-2-spike 1 protein akin to ACE2

description: COVID-19 is caused by the highly contagious <i>SARS-CoV-2</i> virus, which originated in Wuhan, China, resulting in the highest worldwide mortality rate. Gustatory dysfunction is common among individuals infected with the <i>Wild-type Wuhan</i> strain. However, there are no reported cases of gustatory dysfunction among patients infected with the <i>mutant delta</i> variant. The reason behind this remains elusive to date. This <i>in-silico</i>-based study aims to unravel this clinical factor by evaluating the overall binding affinity of predominant bitter taste receptors associated with gustatory function (<i>T2R-4</i>, <i>10</i>, <i>14</i>, <i>19</i>, <i>31</i>, <i>38</i>, <i>43</i>, and <i>46</i>) with the Receptor Binding Domain (<i>RBD</i>) of spike 1 (<i>S1</i>) protein of <i>Wuhan</i> (<i>Wild</i>)/d<i>elta-SARS-CoV-2</i> (<i>mut1</i>-<i>T478K</i>; <i>mut2</i>-<i>E484K</i>) variants. Based on docking and MM/PBSA free binding energy scores, the <i>Wild</i> <i>RBD</i> showed a stronger interaction with <i>T2R-46</i> compared to the <i>ACE2</i> protein. However, both d<i>elta</i> variant mutants (<i>mut1</i> and <i>mut2</i>) could not establish a stronger binding affinity with bitter taste receptor proteins, except for <i>T2R-43</i> against <i>mut1</i>. In conclusion, the <i>delta</i> variants could not establish a better binding affinity with bitter taste receptors, contradicting the <i>Wild</i> variant that determines the severity of gustatory dysfunction among patients exposed to the d<i>elta</i> and <i>Wild SARS-CoV-2</i> variants. The study’s inference also proposes <i>T2R-46</i> as an alternate binding receptor target for <i>RBD-S1</i> of <i>Wild SARS-CoV-2</i>, augmenting its virulence in all functional organs with compromised <i>α-gustducin</i> interaction and bitter sensitization. This <i>in-silico</i>-based study needs further wet-lab-based validation for a better understanding of the role of <i>T2R-46</i>-based viral entry in the human host.
DOI: 10.6084/m9.figshare.24961480.v1
title: Bitter taste receptors establish a stable binding affinity with the SARS-CoV-2-spike 1 protein akin to ACE2

description: COVID-19 is caused by the highly contagious <i>SARS-CoV-2</i> virus, which originated in Wuhan, China, resulting in the highest worldwide mortality rate. Gustatory dysfunction is common among individuals infected with the <i>Wild-type Wuhan</i> strain. However, there are no reported cases of gustatory dysfunction among patients infected with the <i>mutant delta</i> variant. The reason behind this remains elusive to date. This <i>in-silico</i>-based study aims to unravel this clinical factor by evaluating the overall binding affinity of predominant bitter taste receptors associated with gustatory function (<i>T2R-4</i>, <i>10</i>, <i>14</i>, <i>19</i>, <i>31</i>, <i>38</i>, <i>43</i>, and <i>46</i>) with the Receptor Binding Domain (<i>RBD</i>) of spike 1 (<i>S1</i>) protein of <i>Wuhan</i> (<i>Wild</i>)/d<i>elta-SARS-CoV-2</i> (<i>mut1</i>-<i>T478K</i>; <i>mut2</i>-<i>E484K</i>) variants. Based on docking and MM/PBSA free binding energy scores, the <i>Wild</i> <i>RBD</i> showed a stronger interaction with <i>T2R-46</i> compared to the <i>ACE2</i> protein. However, both d<i>elta</i> variant mutants (<i>mut1</i> and <i>mut2</i>) could not establish a stronger binding affinity with bitter taste receptor proteins, except for <i>T2R-43</i> against <i>mut1</i>. In conclusion, the <i>delta</i> variants could not establish a better binding affinity with bitter taste receptors, contradicting the <i>Wild</i> variant that determines the severity of gustatory dysfunction among patients exposed to the d<i>elta</i> and <i>Wild SARS-CoV-2</i> variants. The study’s inference also proposes <i>T2R-46</i> as an alternate binding receptor target for <i>RBD-S1</i> of <i>Wild SARS-CoV-2</i>, augmenting its virulence in all functional organs with compromised <i>α-gustducin</i> interaction and bitter sensitization. This <i>in-silico</i>-based study needs further wet-lab-based validation for a better understanding of the role of <i>T2R-46</i>-based viral entry in the human host.
DOI: 10.6084/m9.figshare.24961156
title: An <i>in silico</i> analysis of the interaction of marine sponge-derived bioactive compounds with type 2 diabetes mellitus targets DPP-4 and PTP1B

description: Type 2 diabetes is a medical condition involving elevated blood glucose levels resulting from impaired or improper insulin utilization. As the number of type 2 diabetes cases increases each year, there is an urgent need to develop novel drugs having new targets and/or complementing existing therapeutic protocols. In this regard, marine sponge-derived compounds hold great potential due to their potent biological activity and structural diversity. In this study, a small library of 50 marine sponge-derived compounds were examined for their activity towards type 2 diabetes targets, namely dipeptidyl peptidase-4 (DPP-4) and protein tyrosine phosphatase 1B (PTP1B). The compounds were first subjected to molecular docking on protein models based on their respective co-crystal structures to assess binding free energies (BFE) and conformations. Clustering analysis yielded BFE that ranged from 24.54 kcal/mol to −9.97 kcal/mol for DPP-4, and from −4.98 kcal/mol to −8.67 kcal/mol for PTP1B. Interaction analysis on the top ten compounds with the most negative BFE towards each protein target showed similar intermolecular interactions and key interacting residues as in the previously solved co-crystal structure. These compounds were subjected to absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling to characterize drug-likeness and combining the results from these analyses, (<i>S</i>)-6’-debromohamacanthin B was identified as a potential multi-target inhibitor of DPP-4 and PTP1B, having favorable protein interaction, no Lipinski violations, good gastrointestinal (GI) tract absorption, blood-brain barrier (BBB) penetration, and no predicted toxicity. Finally, the interaction of (<i>S</i>)-6’-debromohamacanthin B with the two proteins was validated using molecular dynamics simulations over 100 ns through RMSD, radius of gyration, PCA, and molecular mechanics Poisson-Boltzmann surface area (MMPBSA) confirming favorable interactions with the respective proteins. A 50-compound library previously reported from marine sponges was docked to putative T2DM targets, DDP-4 and PTP1B.(<i>S</i>)-6’-debromohamacanthin B was identified as a probable dual-targeting compound based on binding interactions and ADMET evaluation.Interaction of (<i>S</i>)-6’-debromohamacanthin B with DPP-4 and PTP1B was validated by MD simulations. A 50-compound library previously reported from marine sponges was docked to putative T2DM targets, DDP-4 and PTP1B. (<i>S</i>)-6’-debromohamacanthin B was identified as a probable dual-targeting compound based on binding interactions and ADMET evaluation. Interaction of (<i>S</i>)-6’-debromohamacanthin B with DPP-4 and PTP1B was validated by MD simulations.
DOI: 10.6084/m9.figshare.24961156.v1
title: An <i>in silico</i> analysis of the interaction of marine sponge-derived bioactive compounds with type 2 diabetes mellitus targets DPP-4 and PTP1B

description: Type 2 diabetes is a medical condition involving elevated blood glucose levels resulting from impaired or improper insulin utilization. As the number of type 2 diabetes cases increases each year, there is an urgent need to develop novel drugs having new targets and/or complementing existing therapeutic protocols. In this regard, marine sponge-derived compounds hold great potential due to their potent biological activity and structural diversity. In this study, a small library of 50 marine sponge-derived compounds were examined for their activity towards type 2 diabetes targets, namely dipeptidyl peptidase-4 (DPP-4) and protein tyrosine phosphatase 1B (PTP1B). The compounds were first subjected to molecular docking on protein models based on their respective co-crystal structures to assess binding free energies (BFE) and conformations. Clustering analysis yielded BFE that ranged from 24.54 kcal/mol to −9.97 kcal/mol for DPP-4, and from −4.98 kcal/mol to −8.67 kcal/mol for PTP1B. Interaction analysis on the top ten compounds with the most negative BFE towards each protein target showed similar intermolecular interactions and key interacting residues as in the previously solved co-crystal structure. These compounds were subjected to absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling to characterize drug-likeness and combining the results from these analyses, (<i>S</i>)-6’-debromohamacanthin B was identified as a potential multi-target inhibitor of DPP-4 and PTP1B, having favorable protein interaction, no Lipinski violations, good gastrointestinal (GI) tract absorption, blood-brain barrier (BBB) penetration, and no predicted toxicity. Finally, the interaction of (<i>S</i>)-6’-debromohamacanthin B with the two proteins was validated using molecular dynamics simulations over 100 ns through RMSD, radius of gyration, PCA, and molecular mechanics Poisson-Boltzmann surface area (MMPBSA) confirming favorable interactions with the respective proteins. A 50-compound library previously reported from marine sponges was docked to putative T2DM targets, DDP-4 and PTP1B.(<i>S</i>)-6’-debromohamacanthin B was identified as a probable dual-targeting compound based on binding interactions and ADMET evaluation.Interaction of (<i>S</i>)-6’-debromohamacanthin B with DPP-4 and PTP1B was validated by MD simulations. A 50-compound library previously reported from marine sponges was docked to putative T2DM targets, DDP-4 and PTP1B. (<i>S</i>)-6’-debromohamacanthin B was identified as a probable dual-targeting compound based on binding interactions and ADMET evaluation. Interaction of (<i>S</i>)-6’-debromohamacanthin B with DPP-4 and PTP1B was validated by MD simulations.
DOI: 10.6084/m9.figshare.25027099
title: <i>In silico</i> approaches for predicting natural compounds with therapeutic potential and vaccine candidates against <i>Streptococcus equi</i>

description: Equine strangles is a prevalent disease that affects the upper respiratory in horses and is caused by the Gram-positive bacterium <i>Streptococcus equi</i>. In addition to strangles, other clinical conditions are caused by the two <i>S. equi</i> subspecies, <i>equi</i> and <i>zooepidemicus</i>, which present relevant zoonotic potential. Treatment of infections caused by <i>S. equi</i> has become challenging due to the worldwide spreading of infected horses and the unavailability of effective therapeutics and vaccines. Penicillin treatment is often recommended, but multidrug resistance issues arised. We explored the whole genome sequence of 18 <i>S. equi</i> isolates to identify candidate proteins to be targeted by natural drug-like compounds or explored as immunogens. We considered only proteins shared among the sequenced strains of subspecies <i>equi</i> and <i>zooepidemicus</i>, absent in the equine host and predicted to be essential and involved in virulence. Of these, 4 proteins with cytoplasmic subcellular location were selected for molecular docking with a library of 5008 compounds, while 6 proteins were proposed as prominent immunogens against <i>S. equi</i> due to their probabilities of behaving as adhesins. The molecular docking analyses revealed the best ten ligands for each of the 4 drug target candidates, and they were ranked according to their binding affinities and the number of hydrogen bonds for complex stability. Finally, the natural 5-ring compound C<sub>25</sub>H<sub>20</sub>F<sub>3</sub>N<sub>5</sub>O<sub>3</sub> excelled in molecular dynamics simulations for the increased stability in the interaction with UDP-N-acetylenolpyruvoylglucosamine reductase (MurB). This research paves the way to developing new therapeutics to minimize the impacts caused by <i>S. equi</i> infections.
DOI: 10.6084/m9.figshare.25027099.v1
title: <i>In silico</i> approaches for predicting natural compounds with therapeutic potential and vaccine candidates against <i>Streptococcus equi</i>

description: Equine strangles is a prevalent disease that affects the upper respiratory in horses and is caused by the Gram-positive bacterium <i>Streptococcus equi</i>. In addition to strangles, other clinical conditions are caused by the two <i>S. equi</i> subspecies, <i>equi</i> and <i>zooepidemicus</i>, which present relevant zoonotic potential. Treatment of infections caused by <i>S. equi</i> has become challenging due to the worldwide spreading of infected horses and the unavailability of effective therapeutics and vaccines. Penicillin treatment is often recommended, but multidrug resistance issues arised. We explored the whole genome sequence of 18 <i>S. equi</i> isolates to identify candidate proteins to be targeted by natural drug-like compounds or explored as immunogens. We considered only proteins shared among the sequenced strains of subspecies <i>equi</i> and <i>zooepidemicus</i>, absent in the equine host and predicted to be essential and involved in virulence. Of these, 4 proteins with cytoplasmic subcellular location were selected for molecular docking with a library of 5008 compounds, while 6 proteins were proposed as prominent immunogens against <i>S. equi</i> due to their probabilities of behaving as adhesins. The molecular docking analyses revealed the best ten ligands for each of the 4 drug target candidates, and they were ranked according to their binding affinities and the number of hydrogen bonds for complex stability. Finally, the natural 5-ring compound C<sub>25</sub>H<sub>20</sub>F<sub>3</sub>N<sub>5</sub>O<sub>3</sub> excelled in molecular dynamics simulations for the increased stability in the interaction with UDP-N-acetylenolpyruvoylglucosamine reductase (MurB). This research paves the way to developing new therapeutics to minimize the impacts caused by <i>S. equi</i> infections. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.25027099.v2
title: <i>In silico</i> approaches for predicting natural compounds with therapeutic potential and vaccine candidates against <i>Streptococcus equi</i>

description: Equine strangles is a prevalent disease that affects the upper respiratory in horses and is caused by the Gram-positive bacterium <i>Streptococcus equi</i>. In addition to strangles, other clinical conditions are caused by the two <i>S. equi</i> subspecies, <i>equi</i> and <i>zooepidemicus</i>, which present relevant zoonotic potential. Treatment of infections caused by <i>S. equi</i> has become challenging due to the worldwide spreading of infected horses and the unavailability of effective therapeutics and vaccines. Penicillin treatment is often recommended, but multidrug resistance issues arised. We explored the whole genome sequence of 18 <i>S. equi</i> isolates to identify candidate proteins to be targeted by natural drug-like compounds or explored as immunogens. We considered only proteins shared among the sequenced strains of subspecies <i>equi</i> and <i>zooepidemicus</i>, absent in the equine host and predicted to be essential and involved in virulence. Of these, 4 proteins with cytoplasmic subcellular location were selected for molecular docking with a library of 5008 compounds, while 6 proteins were proposed as prominent immunogens against <i>S. equi</i> due to their probabilities of behaving as adhesins. The molecular docking analyses revealed the best ten ligands for each of the 4 drug target candidates, and they were ranked according to their binding affinities and the number of hydrogen bonds for complex stability. Finally, the natural 5-ring compound C<sub>25</sub>H<sub>20</sub>F<sub>3</sub>N<sub>5</sub>O<sub>3</sub> excelled in molecular dynamics simulations for the increased stability in the interaction with UDP-N-acetylenolpyruvoylglucosamine reductase (MurB). This research paves the way to developing new therapeutics to minimize the impacts caused by <i>S. equi</i> infections.
DOI: 10.6084/m9.figshare.24941414
title: Integration analysis of PLAUR as a sunitinib resistance and macrophage related biomarker in ccRCC, an in silicon and experimental study

description: Sunitinib remains the preferred systemic treatment option for specific patients with advanced RCC who are ineligible for immune therapy. However, it’s essential to recognize that Sunitinib fails to elicit a favourable response in all patients. Moreover, most patients eventually develop resistance to Sunitinib. Therefore, identifying new targets associated with Sunitinib resistance is crucial. Utilizing multiple datasets from public cohorts, we conducted an exhaustive analysis and identified a total of 8 microRNAs and 112 mRNAs displaying significant expression differences between Sunitinib responsive and resistant groups. A particular set of six genes, specifically NIPSNAP1, STK40, SDC4, NEU1, TBC1D9, and PLAUR, were identified as highly significant <i>via</i> WGCNA. To delve deeper into the resistance mechanisms, we performed additional investigations using cell, molecular, and flow cytometry tests. These studies confirmed PLAUR's pivotal role in fostering Sunitinib resistance, both <i>in vitro</i> and <i>in vivo</i>. Our findings suggest that PLAUR could be a promising therapeutic target across various cancer types. In conclusion, this investigation not only uncovers vital genes and microRNAs associated with Sunitinib resistance in RCC but also introduces PLAUR as a prospective therapeutic target for diverse cancers. The outcomes contribute to advancing personalized healthcare and developing superior therapeutic strategies.