LIVIVO - Search results -

Search results

Result 1 - 10 of total 14

Search options

Article: Use of physiological based pharmacokinetic modeling for cross-species prediction of pharmacokinetic and tissue distribution profiles of a novel niclosamide prodrug.

Yang, Mengbi / Wang, Amy Q / Padilha, Elias C / Shah, Pranav / Hagen, Natalie R / Ryu, China / Shamim, Khalida / Huang, Wenwei / Xu, Xin

Frontiers in pharmacology

2023 Volume 14, Page(s) 1099425

Abstract: Introduction: ...

Abstract	Introduction:
Language	English
Publishing date	2023-04-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2023.1099425
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.

Article: Identification of natural compounds as potent inhibitors of SARS-CoV-2 main protease using combined docking and molecular dynamics simulations.

Jairajpuri, Deeba Shamim / Hussain, Afzal / Nasreen, Khalida / Mohammad, Taj / Anjum, Farah / Tabish Rehman, Md / Mustafa Hasan, Gulam / Alajmi, Mohamed F / Imtaiyaz Hassan, Md

Saudi journal of biological sciences

2021 Volume 28, Issue 4, Page(s) 2423–2431

Abstract: Coronavirus disease 2019 (COVID-19) has emerged from China and globally affected the entire population through the human-to-human transmission of a newly emerged virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The genome of ... ...

Abstract	Coronavirus disease 2019 (COVID-19) has emerged from China and globally affected the entire population through the human-to-human transmission of a newly emerged virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The genome of SARS-CoV-2 encodes several proteins that are essential for multiplication and pathogenesis. The main protease (M
Language	English
Publishing date	2021-01-27
Publishing country	Saudi Arabia
Document type	Journal Article
ZDB-ID	2515206-3
ISSN	2213-7106 ; 1319-562X
ISSN (online)	2213-7106
ISSN	1319-562X
DOI	10.1016/j.sjbs.2021.01.040
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Identification of natural compounds as potent inhibitors of SARS-CoV-2 main protease using combined docking and molecular dynamics simulations

Deeba Shamim Jairajpuri / Afzal Hussain / Khalida Nasreen / Taj Mohammad / Farah Anjum / Md. Tabish Rehman / Gulam Mustafa Hasan / Mohamed F. Alajmi / Md. Imtaiyaz Hassan

Saudi Journal of Biological Sciences, Vol 28, Iss 4, Pp 2423-

2021 Volume 2431

Abstract	Coronavirus disease 2019 (COVID-19) has emerged from China and globally affected the entire population through the human-to-human transmission of a newly emerged virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The genome of SARS-CoV-2 encodes several proteins that are essential for multiplication and pathogenesis. The main protease (Mpro or 3CLpro) of SARS-CoV-2 plays a central role in its pathogenesis and thus is considered as an attractive drug target for the drug design and development of small-molecule inhibitors. We have employed an extensive structure-based high-throughput virtual screening to discover potential natural compounds from the ZINC database which could inhibit the Mpro of SARS-CoV-2. Initially, the hits were selected on the basis of their physicochemical and drug-like properties. Subsequently, the PAINS filter, estimation of binding affinities using molecular docking, and interaction analyses were performed to find safe and potential inhibitors of SARS-CoV-2 Mpro. We have identified ZINC02123811 (1-(3-(2,5,9-trimethyl-7-oxo-3-phenyl-7H-furo[3,2-g]chromen-6-yl)propanoyl)piperidine-4-carboxamide), a natural compound bearing appreciable affinity, efficiency, and specificity towards the binding pocket of SARS-CoV-2 Mpro. The identified compound showed a set of drug-like properties and preferentially binds to the active site of SARS-CoV-2 Mpro. All-atom molecular dynamics (MD) simulations were performed to evaluate the conformational dynamics, stability and interaction mechanism of Mpro with ZINC02123811. MD simulation results indicated that Mpro with ZINC02123811 forms a stable complex throughout the trajectory of 100 ns. These findings suggest that ZINC02123811 may be further exploited as a promising scaffold for the development of potential inhibitors of SARS-CoV-2 Mpro to address COVID-19.
Keywords	SARS-CoV-2 main protease ; Natural compounds ; Drug discovery ; Virtual high-throughput screening ; Molecular dynamics simulation ; Small molecule inhibitors ; Biology (General) ; QH301-705.5
Subject code	540
Language	English
Publishing date	2021-04-01T00:00:00Z
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: Massive-scale biological activity-based modeling identifies novel antiviral leads against SARS-CoV-2.

Huang, Ruili / Xu, Miao / Zhu, Hu / Chen, Catherine Z / Lee, Emily M / He, Shihua / Shamim, Khalida / Bougie, Danielle / Huang, Wenwei / Hall, Mathew D / Lo, Donald / Simeonov, Anton / Austin, Christopher P / Qiu, Xiangguo / Tang, Hengli / Zheng, Wei

bioRxiv : the preprint server for biology

2020

Abstract: The recent global pandemic caused by the new coronavirus SARS-CoV-2 presents an urgent need for new therapeutic candidates. While the importance of ... ...

Abstract	The recent global pandemic caused by the new coronavirus SARS-CoV-2 presents an urgent need for new therapeutic candidates. While the importance of traditional
Keywords	covid19
Language	English
Publishing date	2020-07-27
Publishing country	United States
Document type	Preprint
DOI	10.1101/2020.07.27.223578
Database	MEDical Literature Analysis and Retrieval System OnLINE

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.

Details ▾

Article ; Online: Biological activity-based modeling identifies antiviral leads against SARS-CoV-2.

Nature biotechnology

2021 Volume 39, Issue 6, Page(s) 747–753

Abstract: Computational approaches for drug discovery, such as quantitative structure-activity relationship, rely on structural similarities of small molecules to infer biological activity but are often limited to identifying new drug candidates in the chemical ... ...

Abstract	Computational approaches for drug discovery, such as quantitative structure-activity relationship, rely on structural similarities of small molecules to infer biological activity but are often limited to identifying new drug candidates in the chemical spaces close to known ligands. Here we report a biological activity-based modeling (BABM) approach, in which compound activity profiles established across multiple assays are used as signatures to predict compound activity in other assays or against a new target. This approach was validated by identifying candidate antivirals for Zika and Ebola viruses based on high-throughput screening data. BABM models were then applied to predict 311 compounds with potential activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Of the predicted compounds, 32% had antiviral activity in a cell culture live virus assay, the most potent compounds showing a half-maximal inhibitory concentration in the nanomolar range. Most of the confirmed anti-SARS-CoV-2 compounds were found to be viral entry inhibitors and/or autophagy modulators. The confirmed compounds have the potential to be further developed into anti-SARS-CoV-2 therapies.
MeSH term(s)	Antiviral Agents/pharmacology ; COVID-19/genetics ; COVID-19/virology ; Drug Discovery/methods ; Drug Evaluation, Preclinical/methods ; High-Throughput Screening Assays/methods ; Humans ; SARS-CoV-2/drug effects ; SARS-CoV-2/pathogenicity ; COVID-19 Drug Treatment
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2021-02-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	1311932-1
ISSN	1546-1696 ; 1087-0156
ISSN (online)	1546-1696
ISSN	1087-0156
DOI	10.1038/s41587-021-00839-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2167: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 137: Show issues
Zs.MG 43: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Efforts toward the total synthesis of (-)-kendomycin.

Williams, David R / Shamim, Khalida

Organic letters

2005 Volume 7, Issue 19, Page(s) 4161–4164

Abstract: structure: see text] The synthesis of an advanced component leading to (-)-kendomycin is described. The synthetic scheme features the application of asymmetric conjugate addition methodology for the early generation of the C13-C14 (E)-trisubstituted ... ...

Abstract	[structure: see text] The synthesis of an advanced component leading to (-)-kendomycin is described. The synthetic scheme features the application of asymmetric conjugate addition methodology for the early generation of the C13-C14 (E)-trisubstituted olefin, providing an efficient assembly of the ansa chain. Condensation reactions probe two strategies for attachment of the aromatic system.
MeSH term(s)	Aldehydes/chemistry ; Alkenes/chemistry ; Molecular Structure ; Rifabutin/analogs & derivatives ; Rifabutin/chemical synthesis ; Rifabutin/chemistry
Chemical Substances	Aldehydes ; Alkenes ; kendomycin ; Rifabutin (1W306TDA6S)
Language	English
Publishing date	2005-09-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1523-7060
ISSN	1523-7060
DOI	10.1021/ol051512r
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: Application of niclosamide and analogs as small molecule inhibitors of Zika virus and SARS-CoV-2 infection.

Bioorganic & medicinal chemistry letters

2021 Volume 40, Page(s) 127906

Abstract: Zika virus has emerged as a potential threat to human health globally. A previous drug repurposing screen identified the approved anthelminthic drug niclosamide as a small molecule inhibitor of Zika virus infection. However, as antihelminthic drugs are ... ...

Abstract	Zika virus has emerged as a potential threat to human health globally. A previous drug repurposing screen identified the approved anthelminthic drug niclosamide as a small molecule inhibitor of Zika virus infection. However, as antihelminthic drugs are generally designed to have low absorption when dosed orally, the very limited bioavailability of niclosamide will likely hinder its potential direct repurposing as an antiviral medication. Here, we conducted SAR studies focusing on the anilide and salicylic acid regions of niclosamide to improve physicochemical properties such as microsomal metabolic stability, permeability and solubility. We found that the 5-bromo substitution in the salicylic acid region retains potency while providing better drug-like properties. Other modifications in the anilide region with 2'-OMe and 2'-H substitutions were also advantageous. We found that the 4'-NO
MeSH term(s)	Animals ; Antiviral Agents/chemical synthesis ; Antiviral Agents/metabolism ; Antiviral Agents/pharmacology ; Binding Sites ; Chlorocebus aethiops ; Drug Stability ; Humans ; Microbial Sensitivity Tests ; Microsomes, Liver/metabolism ; Molecular Docking Simulation ; Molecular Structure ; Niclosamide/analogs & derivatives ; Niclosamide/metabolism ; Niclosamide/pharmacology ; Protein Binding ; Rats ; SARS-CoV-2/drug effects ; Serine Endopeptidases/chemistry ; Serine Endopeptidases/metabolism ; Structure-Activity Relationship ; Vero Cells ; Viral Nonstructural Proteins/chemistry ; Viral Nonstructural Proteins/metabolism ; Viral Proteins/chemistry ; Viral Proteins/metabolism ; Zika Virus/drug effects
Chemical Substances	Antiviral Agents ; NS1 protein, zika virus ; Viral Nonstructural Proteins ; Viral Proteins ; Niclosamide (8KK8CQ2K8G) ; NS3 protein, zika virus (EC 3.4.-) ; Serine Endopeptidases (EC 3.4.21.-)
Language	English
Publishing date	2021-03-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1063195-1
ISSN	1464-3405 ; 0960-894X
ISSN (online)	1464-3405
ISSN	0960-894X
DOI	10.1016/j.bmcl.2021.127906
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3203: 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 ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Discovery of 3-(4-sulfamoylnaphthyl)pyrazolo[1,5-a]pyrimidines as potent and selective ALK2 inhibitors.

Jiang, Jian-Kang / Huang, Xiuli / Shamim, Khalida / Patel, Paresma R / Lee, Arthur / Wang, Amy Q / Nguyen, Kimloan / Tawa, Gregory / Cuny, Gregory D / Yu, Paul B / Zheng, Wei / Xu, Xin / Sanderson, Philip / Huang, Wenwei

Bioorganic & medicinal chemistry letters

2018 Volume 28, Issue 20, Page(s) 3356–3362

Abstract: The pyrazolo[1,5-a]pyrimidine LDN-193189 is a potent inhibitor of activin receptor-like kinase 2 (ALK2) but is nonselective for highly homologous ALK3 and shows only modest kinome selectivity. Herein, we describe the discovery of a novel series of potent ...

Abstract	The pyrazolo[1,5-a]pyrimidine LDN-193189 is a potent inhibitor of activin receptor-like kinase 2 (ALK2) but is nonselective for highly homologous ALK3 and shows only modest kinome selectivity. Herein, we describe the discovery of a novel series of potent and selective ALK2 inhibitors by replacing the quinolinyl with a 4-(sulfamoyl)naphthyl, yielding ALK2 inhibitors that exhibit not only excellent discrimination versus ALK3 but also high kinome selectivity. In addition, the optimized compound 23 demonstrates good ADME and in vivo pharmacokinetic properties.
MeSH term(s)	Activin Receptors, Type I/antagonists & inhibitors ; Activin Receptors, Type I/chemistry ; Animals ; Binding Sites ; Drug Discovery ; Humans ; Mice, Inbred C57BL ; Molecular Structure ; Protein Kinase Inhibitors/chemical synthesis ; Protein Kinase Inhibitors/chemistry ; Protein Kinase Inhibitors/pharmacokinetics ; Protein Kinase Inhibitors/pharmacology ; Pyrazoles/chemical synthesis ; Pyrazoles/chemistry ; Pyrazoles/pharmacokinetics ; Pyrazoles/pharmacology ; Pyrimidines/chemical synthesis ; Pyrimidines/chemistry ; Pyrimidines/pharmacokinetics ; Pyrimidines/pharmacology ; Structure-Activity Relationship ; Sulfonamides/chemical synthesis ; Sulfonamides/chemistry ; Sulfonamides/pharmacokinetics ; Sulfonamides/pharmacology
Chemical Substances	LDN 193189 ; Protein Kinase Inhibitors ; Pyrazoles ; Pyrimidines ; Sulfonamides ; ACVR1 protein, human (EC 2.7.11.30) ; Activin Receptors, Type I (EC 2.7.11.30) ; Acvr1 protein, mouse (EC 2.7.11.30)
Language	English
Publishing date	2018-09-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1063195-1
ISSN	1464-3405 ; 0960-894X
ISSN (online)	1464-3405
ISSN	0960-894X
DOI	10.1016/j.bmcl.2018.09.006
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3203: 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 ▾
- See ZB MED holdings
- Order with fees

Article: The SARS-CoV-2 cytopathic effect is blocked with autophagy modulators.

bioRxiv : the preprint server for biology

2020

Abstract: SARS-CoV-02 is a new type of coronavirus capable of rapid transmission and causing severe clinical symptoms; much of which has unknown biological etiology. It has prompted researchers to rapidly mobilize their efforts towards identifying and developing ... ...

Abstract	SARS-CoV-02 is a new type of coronavirus capable of rapid transmission and causing severe clinical symptoms; much of which has unknown biological etiology. It has prompted researchers to rapidly mobilize their efforts towards identifying and developing anti-viral therapeutics and vaccines. Discovering and understanding the virus' pathways of infection, host-protein interactions, and cytopathic effects will greatly aid in the design of new therapeutics to treat COVID-19. While it is known that chloroquine and hydroxychloroquine, extensively explored as clinical agents for COVID-19, have multiple cellular effects including inhibiting autophagy, there are also dose-limiting toxicities in patients that make clearly establishing their potential mechanisms-of-action problematic. Therefore, we evaluated a range of other autophagy modulators to identify an alternative autophagy-based drug repurposing opportunity. In this work, we found that 6 of these compounds blocked the cytopathic effect of SARS-CoV-2 in Vero-E6 cells with EC
Keywords	covid19
Language	English
Publishing date	2020-05-28
Publishing country	United States
Document type	Preprint
DOI	10.1101/2020.05.16.091520
Database	MEDical Literature Analysis and Retrieval System OnLINE

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.

Details ▾

Article ; Online: Massive-scale biological activity-based modeling identifies novel antiviral leads against SARS-CoV-2

Huang, Ruili / Xu, Miao / Zhu, Hu / Chen, Catherine Z / Lee, Emily / He, Shihua / Shamim, Khalida / Bougie, Danielle / Huang, Wenwei / Hall, Matthew / Lo, Donald / Simeonov, Anton / Austin, Chris / Qiu, Xiangguo / Tang, Hengli / Zheng, Wei

bioRxiv

Abstract: The recent global pandemic caused by the new coronavirus SARS-CoV-2 presents an urgent need for new therapeutic candidates. While the importance of traditional in silico approaches such as QSAR in such efforts in unquestionable, these models ... ...

Abstract	The recent global pandemic caused by the new coronavirus SARS-CoV-2 presents an urgent need for new therapeutic candidates. While the importance of traditional in silico approaches such as QSAR in such efforts in unquestionable, these models fundamentally rely on structural similarity to infer biological activity and are thus prone to becoming trapped in the very nearby chemical spaces of already known ligands. For novel and unprecedented threats such as COVID-19 much faster and efficient paradigms must be devised to accelerate the identification of new chemical classes for rapid drug development. Here we report the development of a new biological activity-based modeling (BABM) approach that builds on the hypothesis that compounds with similar activity patterns tend to share similar targets or mechanisms of action. In BABM, compound activity profiles established on massive scale across multiple assays are used as signatures to predict compound activity in a new assay or against a new target. We first trained and validated this approach by identifying new antiviral lead candidates for Zika and Ebola based on data from ~0.5 million compounds screened against ~2,000 assays. BABM models were then applied to predict ~300 compounds not previously reported to have activity for SARS-CoV-2, which were then tested in a live virus assay with high (>30%) hit rates. The most potent compounds showed antiviral activities in the nanomolar range. These potent confirmed compounds have the potential to be further developed in novel chemical space into new anti-SARS-CoV-2 therapies. These results demonstrate unprecedented ability using BABM to predict novel structures as chemical leads significantly beyond traditional methods, and its application in rapid drug discovery response in a global public health crisis.
Keywords	covid19
Language	English
Publishing date	2020-07-27
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2020.07.27.223578
Database	COVID19

Full text online

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.

To top

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Inter-library loan at ZB MED

Full text online

Kategorien

Inter-library loan at ZB MED