LIVIVO - Search results -

Search results

Result 1 - 10 of total 26

Search options

Article ; Online: Dual targeting of 3CLpro and PLpro of SARS-CoV-2

Sajjan Rajpoot / Manikandan Alagumuthu / Mirza S. Baig

Current Research in Structural Biology, Vol 3, Iss , Pp 9-

A novel structure-based design approach to treat COVID-19

2021 Volume 18

Abstract: With the rapid growth of the COVID-19 (coronavirus disease 2019) pandemic across the globe, therapeutic attention must be directed to fight the novel severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). However, developing new antiviral drugs ... ...

Abstract	With the rapid growth of the COVID-19 (coronavirus disease 2019) pandemic across the globe, therapeutic attention must be directed to fight the novel severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). However, developing new antiviral drugs and vaccines is time-consuming, so one of the best solutions to tackle this virus at present is to repurpose ready-to-use drugs. This paper proposes the repurposing of the Food and Drug Administration (FDA)-approved, purchasable, and naturally occurring drugs for preventive and therapeutic use. We propose to design a dual-inhibitor for the SARS-CoV-2 cysteine proteases—3 Chemotrypsin-like protease or main protease (3CLpro or Mpro) and Papain-like protease (PLpro) responsible for processing the translated polyprotein chain from the viral RNA yielding functional viral proteins. For virtual screening, an unbiased blind docking was performed from which the top nine dual-targeting inhibitors for 3CLpro and PLpro were selected. The nine repurposed drugs, block the catalytic dyad (His41 and Cys145) of 3CLpro as well as the catalytic triad (Cys111, His272, and Asp286) of PLpro. Repurposing known drugs will not only pave the way for rapid in-vitro and in-vivo studies to battle the SARS-CoV-2 but will also expedite the quest for a potent anti-coronaviral drug.
Keywords	COVID-19 ; SARS-CoV-2 ; 3CLpro ; PLpro ; Therapeutic candidates ; Repurposing ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Dual targeting of 3CL

Rajpoot, Sajjan / Alagumuthu, Manikandan / Baig, Mirza S

Current research in structural biology

2020 Volume 3, Page(s) 9–18

Abstract	With the rapid growth of the COVID-19 (coronavirus disease 2019) pandemic across the globe, therapeutic attention must be directed to fight the novel severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). However, developing new antiviral drugs and vaccines is time-consuming, so one of the best solutions to tackle this virus at present is to repurpose ready-to-use drugs. This paper proposes the repurposing of the Food and Drug Administration (FDA)-approved, purchasable, and naturally occurring drugs for preventive and therapeutic use. We propose to design a dual-inhibitor for the SARS-CoV-2 cysteine proteases-3 Chemotrypsin-like protease or main protease (3CL
Language	English
Publishing date	2020-12-10
Publishing country	Netherlands
Document type	Journal Article
ISSN	2665-928X
ISSN (online)	2665-928X
DOI	10.1016/j.crstbi.2020.12.001
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: Structure-Based Design of Novel Peptidomimetics Targeting the SARS-CoV-2 Spike Protein.

Alagumuthu, Manikandan / Rajpoot, Sajjan / Baig, Mirza S

Cellular and molecular bioengineering

2020 Volume 14, Issue 2, Page(s) 177–185

Abstract: Purpose: SARS-CoV-2 is a SARS-like novel coronavirus strain first identified in December 2019 in Wuhan, China. The virus has since spread globally, resulting in the current ongoing coronavirus disease 19 (COVID-19) pandemic. SARS-CoV-2 spike protein is ... ...

Abstract	Purpose: SARS-CoV-2 is a SARS-like novel coronavirus strain first identified in December 2019 in Wuhan, China. The virus has since spread globally, resulting in the current ongoing coronavirus disease 19 (COVID-19) pandemic. SARS-CoV-2 spike protein is a critical factor in the COVID-19 pathogenesis Methods: We utilized the information from ACE2-SARS-CoV-2 binary interactions, and based on crucial interacting interface residues, novel peptidomimetics were designed. Results: Top scoring peptidomimetics were found to bind at the ACE2 binding site of the receptor-binding domain (RBD) of SARS-CoV-2 spike protein. Conclusions: The current studies could pave the way for further investigations of these novel and potent compounds against the SARS-CoV-2.
Keywords	covid19
Language	English
Publishing date	2020-10-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2416037-4
ISSN	1865-5033 ; 1865-5025
ISSN (online)	1865-5033
ISSN	1865-5025
DOI	10.1007/s12195-020-00658-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

Order via subito

Details ▾
- Full text online
- Order with fees

Article ; Online: Investigating theobromine as a potential anti-human coronaviral agent.

Li, Jiajing / Wang, Yining / Rajpoot, Sajjan / Lavrijsen, Marla / Pan, Qiuwei / Li, Pengfei / Baig, Mirza S

Microbiology and immunology

2023 Volume 67, Issue 9, Page(s) 404–412

Abstract: Coronaviruses (CoVs) have long been known to infect humans, mainly alpha-CoV and beta-CoV. The vaccines developed for SARS-CoV-2 are likely not effective against other coronavirus species, whereas the risk of the emergence of new strains that may cause ... ...

Abstract	Coronaviruses (CoVs) have long been known to infect humans, mainly alpha-CoV and beta-CoV. The vaccines developed for SARS-CoV-2 are likely not effective against other coronavirus species, whereas the risk of the emergence of new strains that may cause the next epidemic/pandemic is high. The development of antiviral drugs that are effective across different CoVs represents a viable strategy for improving pandemic preparedness. In this study, we aim to identify pan-coronaviral agents by targeting the conserved main protease (Mpro). For drug screening, the catalytic dyad of four human CoVs (HCoVs: SARS-CoV-2, and seasonal CoV NL63, OC43, and 229E) was targeted by molecular docking. The identified leading candidate theobromine, a xanthine derivative, was further tested in cell culture models of coronavirus infection. Theobromine binds strongly with the catalytic dyad (His41 and Cys144/145) of SARS-CoV-2 and HCoV-NL63 Mpro, mildly with HCoV-OC43, but not with HCoV-229E. However, theobromine only shows dose-dependent inhibition in Calu3 cells inoculated with SARS-CoV-2, but not in cells inoculated with seasonal CoVs. Theobromine exerts antiviral activity against coronavirus infections potentially through targeting Mpro. However, the antiviral potency is distinct among different CoVs.
MeSH term(s)	Humans ; Theobromine/pharmacology ; COVID-19 ; SARS-CoV-2 ; Molecular Docking Simulation ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use
Chemical Substances	Theobromine (OBD445WZ5P) ; Antiviral Agents
Language	English
Publishing date	2023-07-06
Publishing country	Australia
Document type	Journal Article
ZDB-ID	224792-6
ISSN	1348-0421 ; 0385-5600
ISSN (online)	1348-0421
ISSN	0385-5600
DOI	10.1111/1348-0421.13086
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ud II Zs.204: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: TIRAP-mediated activation of p38 MAPK in inflammatory signaling.

Rajpoot, Sajjan / Kumar, Ashutosh / Zhang, Kam Y J / Gan, Siew Hua / Baig, Mirza S

Scientific reports

2022 Volume 12, Issue 1, Page(s) 5601

Abstract: The role of TIRAP (toll/interleukin-1 receptor (TIR) domain-containing adapter protein) in macrophage inflammatory signalling has been significantly evolved since its discovery in 2001 due to its dynamic nature and subcellular localization to regulate ... ...

Abstract	The role of TIRAP (toll/interleukin-1 receptor (TIR) domain-containing adapter protein) in macrophage inflammatory signalling has been significantly evolved since its discovery in 2001 due to its dynamic nature and subcellular localization to regulate multiple signaling through several protein-protein interactions (PPIs). Structural analysis of these interactions can reveal a better understanding of their conformational dynamics and the nature of their binding. Tyrosine phosphorylation in the TIR domain of TIRAP is very critical for its function. In toll-like receptor (TLR) 4/2 signalling, Bruton's tyrosine kinase (BTK) and Protein kinase C delta (PKCδ) are known to phosphorylate the Y86, Y106, Y159, and Y187 of TIRAP which is crucial for the downstream function of MAPKs (mitogen-activated protein kinases) activation. The objective of this study is to understand the interaction of TIRAP with p38 MAPK through molecular docking and identify the importance of TIRAP tyrosine phosphorylation in p38 MAPK interaction. In this structural study, we performed an in-silico molecular docking using HADDOCK 2.4, pyDockWEB, ClusPro 2.0, and ZDOCK 3.0.2 tools to unravel the interaction between TIRAP and p38 MAPK. Further, manual in-silico phosphorylations of TIRAP tyrosines; Y86, Y106, Y159, and Y187 was created in the Discovery Studio tool to study the conformational changes in protein docking and their binding affinities with p38 MAPK in comparison to non-phosphorylated state. Our molecular docking and 500 ns of molecular dynamic (MD) simulation study demonstrates that the Y86 phosphorylation (pY86) in TIRAP is crucial in promoting the higher binding affinity (∆G
MeSH term(s)	Membrane Glycoproteins ; Mitogen-Activated Protein Kinases/metabolism ; Molecular Docking Simulation ; Phosphorylation ; Receptors, Interleukin-1 ; Signal Transduction ; p38 Mitogen-Activated Protein Kinases/metabolism
Chemical Substances	Membrane Glycoproteins ; Receptors, Interleukin-1 ; Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Language	English
Publishing date	2022-04-04
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-09528-8
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Repurposing dyphylline as a pan-coronavirus antiviral therapy.

Wang, Yining / Rajpoot, Sajjan / Li, Pengfei / Lavrijsen, Marla / Ma, Zhongren / Hirani, Nik / Saqib, Uzma / Pan, Qiuwei / Baig, Mirza S

Future medicinal chemistry

2022 Volume 14, Issue 10, Page(s) 685–699

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; COVID-19/drug therapy ; Drug Repositioning ; Dyphylline ; Humans ; Pandemics ; SARS-CoV-2
Chemical Substances	Antiviral Agents ; Dyphylline (263T0E9RR9)
Language	English
Publishing date	2022-04-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1756-8927
ISSN (online)	1756-8927
DOI	10.4155/fmc-2021-0311
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Dorzolamide suppresses PKCδ -TIRAP-p38 MAPK signaling axis to dampen the inflammatory response.

Rajpoot, Sajjan / Kumar, Ashutosh / Gaponenko, Vadim / Thurston, Teresa Lm / Mehta, Dolly / Faisal, Syed M / Zhang, Kam Yj / Jha, Hem C / Darwhekar, Gajanan N / Baig, Mirza S

Future medicinal chemistry

2023

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2023-04-27
Publishing country	England
Document type	Journal Article
ISSN	1756-8927
ISSN (online)	1756-8927
DOI	10.4155/fmc-2022-0260
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: TIRAP-mediated activation of p38 MAPK in inflammatory signaling

Sajjan Rajpoot / Ashutosh Kumar / Kam Y. J. Zhang / Siew Hua Gan / Mirza S. Baig

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 15

Abstract: Abstract The role of TIRAP (toll/interleukin-1 receptor (TIR) domain-containing adapter protein) in macrophage inflammatory signalling has been significantly evolved since its discovery in 2001 due to its dynamic nature and subcellular localization to ... ...

Abstract	Abstract The role of TIRAP (toll/interleukin-1 receptor (TIR) domain-containing adapter protein) in macrophage inflammatory signalling has been significantly evolved since its discovery in 2001 due to its dynamic nature and subcellular localization to regulate multiple signaling through several protein–protein interactions (PPIs). Structural analysis of these interactions can reveal a better understanding of their conformational dynamics and the nature of their binding. Tyrosine phosphorylation in the TIR domain of TIRAP is very critical for its function. In toll-like receptor (TLR) 4/2 signalling, Bruton's tyrosine kinase (BTK) and Protein kinase C delta (PKCδ) are known to phosphorylate the Y86, Y106, Y159, and Y187 of TIRAP which is crucial for the downstream function of MAPKs (mitogen-activated protein kinases) activation. The objective of this study is to understand the interaction of TIRAP with p38 MAPK through molecular docking and identify the importance of TIRAP tyrosine phosphorylation in p38 MAPK interaction. In this structural study, we performed an in-silico molecular docking using HADDOCK 2.4, pyDockWEB, ClusPro 2.0, and ZDOCK 3.0.2 tools to unravel the interaction between TIRAP and p38 MAPK. Further, manual in-silico phosphorylations of TIRAP tyrosines; Y86, Y106, Y159, and Y187 was created in the Discovery Studio tool to study the conformational changes in protein docking and their binding affinities with p38 MAPK in comparison to non-phosphorylated state. Our molecular docking and 500 ns of molecular dynamic (MD) simulation study demonstrates that the Y86 phosphorylation (pY86) in TIRAP is crucial in promoting the higher binding affinity (∆Gbind) with p38 MAPK. The conformational changes due to the tyrosine phosphorylation mainly at the Y86 site pull the TIRAP closer to the active site in the kinase domain of p38 MAPK and plays a significant role at the interface site which is reversed in its dephosphorylated state. The heatmap of interactions between the TIRAP and p38 MAPK after the MD ...
Keywords	Medicine ; R ; Science ; Q
Subject code	500
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: Structural analysis of spike proteins from SARS-CoV-2 variants of concern highlighting their functional alterations.

Solanki, Kundan / Rajpoot, Sajjan / Kumar, Ashutosh / J Zhang, Kam Y / Ohishi, Tomokazu / Hirani, Nik / Wadhonkar, Khandu / Patidar, Pramod / Pan, Qiuwei / Baig, Mirza S

Future virology

2022

Abstract: Aim: ...

Abstract	Aim:
Language	English
Publishing date	2022-08-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2254606-6
ISSN	1746-0808 ; 1746-0794
ISSN (online)	1746-0808
ISSN	1746-0794
DOI	10.2217/fvl-2022-0003
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Identification of a Potential Peptide Inhibitor of SARS-CoV-2 Targeting its Entry into the Host Cells.

Baig, Mirza S / Alagumuthu, Manikandan / Rajpoot, Sajjan / Saqib, Uzma

Drugs in R&D

2020 Volume 20, Issue 3, Page(s) 161–169

Abstract: Background and objective: Coronavirus disease (COVID-19) is an ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the incessant spread of the disease with substantial morbidity and mortality rates, there is ... ...

Abstract	Background and objective: Coronavirus disease (COVID-19) is an ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the incessant spread of the disease with substantial morbidity and mortality rates, there is an urgent demand for effective therapeutics and vaccines to control and diminish this pandemic. A critical step in the crosstalk between the virus and the host cell is the binding of SARS-CoV-2 spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor present on the surface of the host cells. Hence, inhibition of this interaction could be a promising strategy to combat the SARS-CoV-2 infection. Methods: Docking and Molecular Dynamics (MD) simulation studies revealed that designed peptide maintains their secondary structure and provide a highly specific and stable binding (blocking) to SARS-CoV-2. Results: We have designed a novel peptide that could inhibit SARS-CoV-2 spike protein interaction with ACE2, thereby blocking the cellular entry of the virus. Conclusion: Our findings suggest that computationally developed inhibitory peptide may be developed as an anti-SARS-CoV-2 agent for the treatment of SARS-CoV-2 infection. We further plan to pursue the peptide in cell-based assays and eventually for clinical trials.
MeSH term(s)	Angiotensin-Converting Enzyme 2 ; Antiviral Agents/pharmacology ; Betacoronavirus/isolation & purification ; Betacoronavirus/metabolism ; COVID-19 ; Coronavirus Infections/prevention & control ; Coronavirus Infections/virology ; Humans ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Pandemics/prevention & control ; Peptides/pharmacology ; Peptidyl-Dipeptidase A/metabolism ; Pneumonia, Viral/prevention & control ; Pneumonia, Viral/virology ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/metabolism ; Viral Vaccines/pharmacology
Chemical Substances	Antiviral Agents ; Peptides ; Spike Glycoprotein, Coronavirus ; Viral Vaccines ; spike protein, SARS-CoV-2 ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Keywords	covid19
Language	English
Publishing date	2020-06-27
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2020476-0
ISSN	1179-6901 ; 1174-5886
ISSN (online)	1179-6901
ISSN	1174-5886
DOI	10.1007/s40268-020-00312-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 5262: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

To top

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito