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Article ; Online: Selective inhibition of peptidyl-arginine deiminase (PAD): can it control multiple inflammatory disorders as a promising therapeutic strategy?

Padhy, Dibya Sundar / Palit, Partha / Ikbal, Abu Md Ashif / Das, Nirupam / Roy, Dilip Kumar / Banerjee, Sugato

2023 Volume 31, Issue 2, Page(s) 731–744

Abstract: Peptidyl arginine deiminases (PADs) are a family of post-translational modification enzymes that irreversibly citrullinate (deiminate) arginine residues of protein and convert them to a non-classical amino acid citrulline in the presence of calcium ions. ...

Abstract	Peptidyl arginine deiminases (PADs) are a family of post-translational modification enzymes that irreversibly citrullinate (deiminate) arginine residues of protein and convert them to a non-classical amino acid citrulline in the presence of calcium ions. It has five isotypes, such as PAD1, PAD2, PAD3, PAD4, and PAD6, found in mammalian species. It has been suggested that increased PAD expression in various tissues contributes to the development of multiple inflammatory diseases, including rheumatoid arthritis (RA), cancer, diabetes, and neurological disorders. Elevation of PAD enzyme expression depends on several factors like rising intracellular Ca
MeSH term(s)	Animals ; Protein-Arginine Deiminases/chemistry ; Protein-Arginine Deiminases/metabolism ; Hydrolases/metabolism ; Proteins ; Arginine ; Mammals/metabolism
Chemical Substances	Protein-Arginine Deiminases (EC 3.5.3.15) ; arginine deiminase (EC 3.5.3.6) ; Hydrolases (EC 3.-) ; Proteins ; Arginine (94ZLA3W45F)
Language	English
Publishing date	2023-02-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1080058-x
ISSN	1568-5608 ; 0925-4692
ISSN (online)	1568-5608
ISSN	0925-4692
DOI	10.1007/s10787-023-01149-5
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Zs.A 3274: Show issues

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Article ; Online: Phyto-pharmacological perspective of Silymarin: A potential prophylactic or therapeutic agent for COVID-19, based on its promising immunomodulatory, anti-coagulant and anti-viral property.

Palit, Partha / Mukhopadhyay, Aparna / Chattopadhyay, Debprasad

Phytotherapy research : PTR

2021 Volume 35, Issue 8, Page(s) 4246–4257

Abstract: Coronavirus disease 2019 (COVID-19) triggered by a new viral pathogen, named severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), is now a global health emergency. This debilitating viral pandemic not only paralyzed the normal daily life of the ... ...

Abstract	Coronavirus disease 2019 (COVID-19) triggered by a new viral pathogen, named severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), is now a global health emergency. This debilitating viral pandemic not only paralyzed the normal daily life of the global community but also spread rapidly via global travel. To date there are no effective vaccines or specific treatments against this highly contagious virus; therefore, there is an urgent need to advocate novel prophylactic or therapeutic interventions for COVID-19. This brief opinion critically discusses the potential of Silymarin, a flavonolignan with diverse pharmacological activity having antiinflammatory, antioxidant, antiplatelet, and antiviral properties, with versatile immune-cytokine regulatory functions, that able to bind with transmembrane protease serine 2 (TMPRSS2) and induce endogenous antiviral cytokine interferon-stimulated gene 15, for the management of COVID-19. Silymarin inhibits the expression of host cell surface receptor TMPRSS2 with a docking binding energy corresponding to -1,350.61 kcal/mol and a full fitness score of -8.11. The binding affinity of silymarin with an impressive virtual score exhibits significant potential to interfere with SARS-CoV-2 replication. We propose in-depth pre-clinical and clinical review studies of silymarin for the development of anti-COVID-19 lead, based on its clinical manifestations of COVID-19 and multifaceted bioactivities.
MeSH term(s)	Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; COVID-19/drug therapy ; COVID-19/prevention & control ; Humans ; Pandemics ; SARS-CoV-2/drug effects ; Silymarin/pharmacology ; Silymarin/therapeutic use
Chemical Substances	Antiviral Agents ; Silymarin
Language	English
Publishing date	2021-04-04
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	639136-9
ISSN	1099-1573 ; 0951-418X
ISSN (online)	1099-1573
ISSN	0951-418X
DOI	10.1002/ptr.7084
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Article: Phyto‐pharmacological perspective of Silymarin: A potential prophylactic or therapeutic agent for COVID‐19, based on its promising immunomodulatory, anti‐coagulant and anti‐viral property

Palit, Partha / Mukhopadhyay, Aparna / Chattopadhyay, Debprasad

Phytotherapy research. 2021 Aug., v. 35, no. 8

2021

Abstract: Coronavirus disease 2019 (COVID‐19) triggered by a new viral pathogen, named severe acute respiratory syndrome Coronavirus‐2 (SARS‐CoV‐2), is now a global health emergency. This debilitating viral pandemic not only paralyzed the normal daily life of the ... ...

Abstract	Coronavirus disease 2019 (COVID‐19) triggered by a new viral pathogen, named severe acute respiratory syndrome Coronavirus‐2 (SARS‐CoV‐2), is now a global health emergency. This debilitating viral pandemic not only paralyzed the normal daily life of the global community but also spread rapidly via global travel. To date there are no effective vaccines or specific treatments against this highly contagious virus; therefore, there is an urgent need to advocate novel prophylactic or therapeutic interventions for COVID‐19. This brief opinion critically discusses the potential of Silymarin, a flavonolignan with diverse pharmacological activity having antiinflammatory, antioxidant, antiplatelet, and antiviral properties, with versatile immune‐cytokine regulatory functions, that able to bind with transmembrane protease serine 2 (TMPRSS2) and induce endogenous antiviral cytokine interferon‐stimulated gene 15, for the management of COVID‐19. Silymarin inhibits the expression of host cell surface receptor TMPRSS2 with a docking binding energy corresponding to −1,350.61 kcal/mol and a full fitness score of −8.11. The binding affinity of silymarin with an impressive virtual score exhibits significant potential to interfere with SARS‐CoV‐2 replication. We propose in‐depth pre‐clinical and clinical review studies of silymarin for the development of anti‐COVID‐19 lead, based on its clinical manifestations of COVID‐19 and multifaceted bioactivities.
Keywords	COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; anticoagulants ; antioxidants ; antiviral properties ; cytokines ; energy ; genes ; lead ; medicinal properties ; pandemic ; pathogens ; phytotherapy ; proteinases ; research ; serine ; silymarin ; travel ; viruses
Language	English
Dates of publication	2021-08
Size	p. 4246-4257.
Publishing place	John Wiley & Sons, Ltd.
Document type	Article
Note	REVIEW
ZDB-ID	639136-9
ISSN	1099-1573 ; 0951-418X
ISSN (online)	1099-1573
ISSN	0951-418X
DOI	10.1002/ptr.7084
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Comprehensive review on recent trends and perspectives of natural exo-polysaccharides: Pioneering nano-biotechnological tools.

Tiwari, Onkar Nath / Bobby, Md Nazneen / Kondi, Vanitha / Halder, Gopinath / Kargarzadeh, Hanieh / Ikbal, Abu Md Ashif / Bhunia, Biswanath / Thomas, Sabu / Efferth, Thomas / Chattopadhyay, Debprasad / Palit, Partha

International journal of biological macromolecules

2024 Volume 265, Issue Pt 2, Page(s) 130747

Abstract: Exopolysaccharides (EPSs), originating from various microbes, and mushrooms, excel in their conventional role in bioremediation to showcase diverse applications emphasizing nanobiotechnology including nano-drug carriers, nano-excipients, medication and/ ... ...

Abstract	Exopolysaccharides (EPSs), originating from various microbes, and mushrooms, excel in their conventional role in bioremediation to showcase diverse applications emphasizing nanobiotechnology including nano-drug carriers, nano-excipients, medication and/or cell encapsulation, gene delivery, tissue engineering, diagnostics, and associated treatments. Acknowledged for contributions to adsorption, nutrition, and biomedicine, EPSs are emerging as appealing alternatives to traditional polymers, for biodegradability and biocompatibility. This article shifts away from the conventional utility to delve deeply into the expansive landscape of EPS applications, particularly highlighting their integration into cutting-edge nanobiotechnological methods. Exploring EPS synthesis, extraction, composition, and properties, the discussion emphasizes their structural diversity with molecular weight and heteropolymer compositions. Their role as raw materials for value-added products takes center stage, with critical insights into recent applications in nanobiotechnology. The multifaceted potential, biological relevance, and commercial applicability of EPSs in contemporary research and industry align with the nanotechnological advancements coupled with biotechnological nano-cleansing agents are highlighted. EPS-based nanostructures for biological applications have a bright future ahead of them. Providing crucial information for present and future practices, this review sheds light on how eco-friendly EPSs derived from microbial biomass of terrestrial and aquatic environments can be used to better understand contemporary nanobiotechnology for the benefit of society.
MeSH term(s)	Polysaccharides, Bacterial/chemistry ; Biotechnology ; Drug Carriers ; Nanostructures ; Nanotechnology
Chemical Substances	Polysaccharides, Bacterial ; Drug Carriers
Language	English
Publishing date	2024-03-12
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2024.130747
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Article: Phytopharmaceuticals mediated Furin and TMPRSS2 receptor blocking: can it be a potential therapeutic option for Covid-19?

Palit, Partha / Chattopadhyay, Debprasad / Thomas, Sabu / Kundu, Amit / Kim, Hyung Sik / Rezaei, Nima

Phytomedicine. 2021 May, v. 85

2021

Abstract: Currently, novel coronavirus disease (Covid-19) outbreak creates global panic across the continents, as people from almost all countries and territories have been affected by this highly contagious viral disease. The scenario is deteriorating due to lack ...

Abstract	Currently, novel coronavirus disease (Covid-19) outbreak creates global panic across the continents, as people from almost all countries and territories have been affected by this highly contagious viral disease. The scenario is deteriorating due to lack of proper & specific target-oriented pharmacologically safe prophylactic agents or drugs, and or any effective vaccine. drug development is urgently required to back in the normalcy in the community and to combat this pandemic.Thus, we have proposed two novel drug targets, Furin and TMPRSS2, as Covid-19 treatment strategy. We have highlighted this target-oriented novel drug delivery strategy, based on their pathophysiological implication on SARS-CoV-2 infection, as evident from earlier SARS-CoV-1, MERS, and influenza virus infection via host cell entry, priming, fusion, and endocytosis.An earlier study suggested that Furin and TMPRSS2 knockout mice had reduced level of viral load and a lower degree of organ damage such as the lung. The present study thus highlights the promise of some selected novel and potential anti-viral Phytopharmaceutical that bind to Furin and TMPRSS2 as target.Few of them had shown promising anti-viral response in both preclinical and clinical study with acceptable therapeutic safety-index.Hence, this strategy may limit life-threatening Covid-19 infection and its mortality rate through nano-suspension based intra-nasal or oral nebulizer spray, to treat mild to moderate SARS-COV-2 infection when Furin and TMPRSS2 receptor may initiate to express and activate for processing the virus to cause cellular infection by replication within the host cell and blocking of host-viral interaction.
Keywords	COVID-19 infection ; Orthomyxoviridae ; Severe acute respiratory syndrome coronavirus ; Severe acute respiratory syndrome coronavirus 2 ; drug development ; lungs ; mortality ; phytopharmaceuticals ; therapeutics ; vaccines ; viral load ; viruses
Language	English
Dates of publication	2021-05
Publishing place	Elsevier GmbH
Document type	Article
Note	NAL-light
ZDB-ID	1205240-1
ISSN	1618-095X ; 0944-7113
ISSN (online)	1618-095X
ISSN	0944-7113
DOI	10.1016/j.phymed.2020.153396
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Zs.A 4115: Show issues

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Article ; Online: Investigation of bio-active Amaryllidaceae alkaloidal small molecules as putative SARS-CoV-2 main protease and host TMPRSS2 inhibitors: interpretation by

Bhowmick, Shovonlal / Mistri, Tapan Kumar / Khan, Mohammad Rizwan / Patil, Pritee Chunarkar / Busquets, Rosa / Ashif Ikbal, Abu Md / Choudhury, Ankita / Roy, Dilip Kumar / Palit, Partha / Saha, Achintya

Journal of biomolecular structure & dynamics

2023 , Page(s) 1–21

Abstract: The novel coronavirus disease 2019 (Covid-19) outburst is still threatening global health. This highly contagious viral disease is caused by the infection of SARS-CoV-2 virus. Covid-19 and post-Covid-19 complications induce noteworthy mortality. ... ...

Abstract	The novel coronavirus disease 2019 (Covid-19) outburst is still threatening global health. This highly contagious viral disease is caused by the infection of SARS-CoV-2 virus. Covid-19 and post-Covid-19 complications induce noteworthy mortality. Potential chemical hits and leads against SARS-CoV-2 for combating Covid-19 are urgently required. In the present study, a virtual-screening protocol was executed on potential Amaryllidaceae alkaloids from a pool of natural compound library against SARS-CoV-2 main protease (M
Language	English
Publishing date	2023-07-24
Publishing country	England
Document type	Journal Article
ZDB-ID	49157-3
ISSN	1538-0254 ; 0739-1102
ISSN (online)	1538-0254
ISSN	0739-1102
DOI	10.1080/07391102.2023.2238065
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Zs.A 2093: Show issues

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Article: Discoidin domain receptor 2: An emerging pharmacological drug target for prospective therapy against osteoarthritis.

Kumar, Amresh / Dutta Choudhury, M / Ghosh, Parasar / Palit, Partha

Pharmacological reports : PR

2019 Volume 71, Issue 3, Page(s) 399–408

Abstract: Discoidin domain receptor2 (DDR2), a cell membrane tyrosine kinase on chondrocytes surface plays main role in cell-ECM interaction during the progressive degeneration of articular cartilage in osteoarthritis. The degraded component of ECM, type II ... ...

Abstract	Discoidin domain receptor2 (DDR2), a cell membrane tyrosine kinase on chondrocytes surface plays main role in cell-ECM interaction during the progressive degeneration of articular cartilage in osteoarthritis. The degraded component of ECM, type II collagen upon DDR2 binding provokes synthesis of matrix metalloproteinases (MMPs), responsible for severe destruction of joint tissues. DDR2 knockout has been investigated to decline the expression of MMP-1 and 13. Previously, various molecules were effective in preclinical level against different targets in OA, but found to be collapsed in clinical trial due to insufficient target specificity and clinical toxicity. Review emphasizes the role of DDR2 in the degeneration of cartilage in osteoarthritis (OA) and its blocking by DDR2 antagonist attenuates the disease severity. DDR2 in chondrocytes contributes paramount role in degradation of cartilage at early stage of osteoarthritis via collagen 2 binding through the felicitation of TGF-β signaling molecule and other triggering factors. DDR2 involvement in regulation of matrix metalloproteinase (MMP), cross talking interaction in maintenance of ECM-chondrocytes, bone developments, interference RNA and designing the DDR2 antagonists have been critically investigated. The exploration may conclude that the DDR2 could be the novel pharmacological target to prevent the progression of osteoarthritis at early stage because of over expression of DDR2 and MMP which further promotes severe cartilage degeneration. Owing to pharmacological specificity of DDR2 in OA as drug target, it is to be hypothesized that development of safe molecules as DDR2 antagonist could be the good option in the treatment of OA with promising landmark.
MeSH term(s)	Animals ; Cartilage, Articular/metabolism ; Discoidin Domain Receptor 2/metabolism ; Disease Progression ; Humans ; Metalloendopeptidases/metabolism ; Osteoarthritis/metabolism ; Prospective Studies
Chemical Substances	Discoidin Domain Receptor 2 (EC 2.7.10.1) ; Metalloendopeptidases (EC 3.4.24.-)
Language	English
Publishing date	2019-01-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2186248-5
ISSN	1734-1140
ISSN	1734-1140
DOI	10.1016/j.pharep.2019.01.007
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Article: Enhancement of immune surveillance in breast cancer by targeting hypoxic tumor endothelium: Can it be an immunological switch point?

Thomas, Juvin Ann / Gireesh Moly, Athira Gireesh / Xavier, Hima / Suboj, Priya / Ladha, Amit / Gupta, Gaurav / Singh, Santosh Kumar / Palit, Partha / Babykutty, Suboj

Frontiers in oncology

2023 Volume 13, Page(s) 1063051

Abstract: Breast cancer ranks second among the causes of cancer-related deaths in women. In spite of the recent advances achieved in the diagnosis and treatment of breast cancer, further study is required to overcome the risk of cancer resistance to treatment and ... ...

Abstract	Breast cancer ranks second among the causes of cancer-related deaths in women. In spite of the recent advances achieved in the diagnosis and treatment of breast cancer, further study is required to overcome the risk of cancer resistance to treatment and thereby improve the prognosis of individuals with advanced-stage breast cancer. The existence of a hypoxic microenvironment is a well-known event in the development of mutagenesis and rapid proliferation of cancer cells. Tumor cells, purposefully cause local hypoxia in order to induce angiogenesis and growth factors that promote tumor growth and metastatic characteristics, while healthy tissue surrounding the tumor suffers damage or mutate. It has been found that these settings with low oxygen levels cause immunosuppression and a lack of immune surveillance by reducing the activation and recruitment of tumor infiltrating leukocytes (TILs). The immune system is further suppressed by hypoxic tumor endothelium through a variety of ways, which creates an immunosuppressive milieu in the tumor microenvironment. Non responsiveness of tumor endothelium to inflammatory signals or endothelial anergy exclude effector T cells from the tumor milieu. Expression of endothelial specific antigens and immunoinhibitory molecules like Programmed death ligand 1,2 (PDL-1, 2) and T cell immunoglobulin and mucin-domain containing-3 (TIM-3) by tumor endothelium adds fuel to the fire by inhibiting T lymphocytes while promoting regulatory T cells. The hypoxic microenvironment in turn recruits Myeloid Derived Suppressor Cells (MDSCs), Tumor Associated Macrophages (TAMs) and T regulatory cells (Treg). The structure and function of newly generated blood vessels within tumors, on the other hand, are aberrant, lacking the specific organization of normal tissue vasculature. Vascular normalisation may work for a variety of tumour types and show to be an advantageous complement to immunotherapy for improving tumour access. By enhancing immune response in the hypoxic tumor microenvironment,
Language	English
Publishing date	2023-03-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2023.1063051
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Article ; Online: Interaction of a Triantennary Quinoline Glycoconjugate with the Asialoglycoprotein Receptor.

Palit, Subhadeep / Banerjee, Sayanika / Mahata, Tridib / Niyogi, Sougata / Das, Tanusree / Sova Mandi, Chandra / Chakrabarti, Partha / Dutta, Sanjay

ChemMedChem

2021 Volume 16, Issue 14, Page(s) 2211–2216

Abstract: Targeted intracellular delivery is an efficient strategy for developing therapeutics against cancer and other intracellular infections. Nonspecific drug delivery shows limited clinical applications owing to high dosage, cytotoxicity, nonspecific action, ... ...

Abstract	Targeted intracellular delivery is an efficient strategy for developing therapeutics against cancer and other intracellular infections. Nonspecific drug delivery shows limited clinical applications owing to high dosage, cytotoxicity, nonspecific action, high cost, etc. Therefore, targeted delivery of less cytotoxic drug candidates to hepatocytes through ASGPR-mediated endocytosis could be an efficient strategy to surmount the prevailing shortcomings. In the present work, the gene encoding ASGPR-H1-CRD was amplified from Huh7 cells, cloned into pET 11a vector, and the ASGPR-H1-CRD protein was expressed and purified from E. coli. A novel triantennary galactose-conjugated quinoline derivative 4 was synthesized that demonstrates 17-fold higher binding affinity to isolated ASGPR-H1-CRD protein receptor (K
MeSH term(s)	Asialoglycoprotein Receptor/metabolism ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Glycoconjugates/chemical synthesis ; Glycoconjugates/chemistry ; Glycoconjugates/pharmacology ; Humans ; Molecular Structure ; Quinolines/chemical synthesis ; Quinolines/chemistry ; Quinolines/pharmacology ; Structure-Activity Relationship
Chemical Substances	Asialoglycoprotein Receptor ; Glycoconjugates ; Quinolines
Language	English
Publishing date	2021-05-05
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2218496-X
ISSN	1860-7187 ; 1860-7179
ISSN (online)	1860-7187
ISSN	1860-7179
DOI	10.1002/cmdc.202100158
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Zs.A 6280: Show issues

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Article ; Online: Phytopharmaceuticals mediated Furin and TMPRSS2 receptor blocking: can it be a potential therapeutic option for Covid-19?

Palit, Partha / Chattopadhyay, Debprasad / Thomas, Sabu / Kundu, Amit / Kim, Hyung Sik / Rezaei, Nima

Phytomedicine : international journal of phytotherapy and phytopharmacology

2020 Volume 85, Page(s) 153396

Abstract: Background: Currently, novel coronavirus disease (Covid-19) outbreak creates global panic across the continents, as people from almost all countries and territories have been affected by this highly contagious viral disease. The scenario is ... ...

Abstract	Background: Currently, novel coronavirus disease (Covid-19) outbreak creates global panic across the continents, as people from almost all countries and territories have been affected by this highly contagious viral disease. The scenario is deteriorating due to lack of proper & specific target-oriented pharmacologically safe prophylactic agents or drugs, and or any effective vaccine. drug development is urgently required to back in the normalcy in the community and to combat this pandemic. Purpose: Thus, we have proposed two novel drug targets, Furin and TMPRSS2, as Covid-19 treatment strategy. We have highlighted this target-oriented novel drug delivery strategy, based on their pathophysiological implication on SARS-CoV-2 infection, as evident from earlier SARS-CoV-1, MERS, and influenza virus infection via host cell entry, priming, fusion, and endocytosis. STUDY DESIGN & METHODS: An earlier study suggested that Furin and TMPRSS2 knockout mice had reduced level of viral load and a lower degree of organ damage such as the lung. The present study thus highlights the promise of some selected novel and potential anti-viral Phytopharmaceutical that bind to Furin and TMPRSS2 as target. Result: Few of them had shown promising anti-viral response in both preclinical and clinical study with acceptable therapeutic safety-index. Conclusion: Hence, this strategy may limit life-threatening Covid-19 infection and its mortality rate through nano-suspension based intra-nasal or oral nebulizer spray, to treat mild to moderate SARS-COV-2 infection when Furin and TMPRSS2 receptor may initiate to express and activate for processing the virus to cause cellular infection by replication within the host cell and blocking of host-viral interaction.
MeSH term(s)	Angiotensin-Converting Enzyme 2/antagonists & inhibitors ; Animals ; COVID-19/drug therapy ; Furin/antagonists & inhibitors ; Furin/metabolism ; Humans ; Mice ; Mice, Knockout ; Phytochemicals/pharmacology ; Receptors, Virus/antagonists & inhibitors ; SARS-CoV-2 ; Serine Endopeptidases/metabolism ; Serine Proteinase Inhibitors/pharmacology ; Spike Glycoprotein, Coronavirus/metabolism
Chemical Substances	Phytochemicals ; Receptors, Virus ; Serine Proteinase Inhibitors ; Spike Glycoprotein, Coronavirus ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, human (EC 3.4.21.-) ; Furin (EC 3.4.21.75)
Language	English
Publishing date	2020-10-28
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	1205240-1
ISSN	1618-095X ; 0944-7113
ISSN (online)	1618-095X
ISSN	0944-7113
DOI	10.1016/j.phymed.2020.153396
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