更新于：2024-11-01

DENV capsid

更新于：2024-11-01

基本信息

别名-

简介-

关联

项与 DENV capsid 相关的药物

Cas13(GSU)

靶点

DENV capsid

作用机制

DENV capsid 抑制剂

在研机构

Georgia State University

原研机构

Georgia State University

在研适应症

登革热

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

DSPD3

靶点

DENV capsid

作用机制

DENV capsid 抑制剂

在研机构

Institute of Himalayan Bioresource Technology

原研机构

Institute of Himalayan Bioresource Technology

在研适应症

登革热

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

ST-148

靶点

DENV capsid

作用机制

DENV capsid 抑制剂

在研机构

SIGA Technologies, Inc.

原研机构

SIGA Technologies, Inc.

在研适应症

登革热

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 DENV capsid 相关的临床结果

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100 项与 DENV capsid 相关的转化医学

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0 项与 DENV capsid 相关的专利（医药）

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项与 DENV capsid 相关的文献（医药）

2023-12-01·International Journal of Biological Macromolecules

Characterization of pH-induced conformational changes in recombinant DENV NS2B-NS3pro

Article

作者: Hisamuddin, Malik ; Khan, Rizwan H ; Khan, Javed Masood ; Ali, Syed Moasfar ; Hassan, Md Nadir ; Nabi, Faisal ; Rizvi, Irum ; Malik, Ajamaluddin ; Khan, Tabish H

The increasing frequency of Dengue is a cause of severe epidemics and therefore demands strategies for effective prevention, diagnosis, and treatment. DENV-protease is being investigated as a potential therapeutic target. However, due to the flat and highly charged active site of the DENV-protease, designing orthosteric medicines is very difficult. In this study, we have done a thorough analysis of pH-dependent conformational changes in recombinantly expressed DENV protease using various spectroscopic techniques. Our spectroscopic study of DENV protease (NS2B-NS3pro) at different pH conditions gives important insights into the dynamicity of structural conformation. At physiological pH, the DENV-protease exists in a random-coiled state. Lowering the pH promotes the formation of alpha-helical and beta-sheet structures i.e. gain of secondary structure as shown by Far-UV CD. The light scattering and Thioflavin T (ThT)-binding assay proved the aggregation-prone tendency of DENV-protease at pH 4.0. Further, the confocal microscopy image intensity showed the amorphous aggregate formation of DENV protease at pH 4.0. Thus, the DENV protease acquires different conformations with changes in pH conditions. Together, these results have the potential to facilitate the design of a conformation destabilizer-based therapeutic strategy for dengue fever.

2023-06-01·Computational Biology and Chemistry

Exploring allosteric hits of the NS2B-NS3 protease of DENV2 by structure-guided screening

Article

作者: Gangopadhyay, Aditi ; Saha, Achintya

Despite the rising number of cases and increasing global disease burden, there is no definitive therapy against dengue to date, which necessitates the urgent discovery of inhibitors against the virus.The NS2B-NS3 serine protease of the dengue virus (DENV) catalyzes polyprotein cleavage and is a potential target for drug discovery.The protease possesses a potentially druggable allosteric site, and the binding of inhibitors to this site locks the protease in an inactive conformation.The allosteric site is a potential druggable target for drug discovery against flaviviruses.This study aimed to identify serotype-specific hits against the allosteric site in the NS2B-NS3 protease of DENV serotype 2 (DENV2) from the Enamine, Selleck, and ChemDiv antiviral libraries.The prepared libraries were screened using a redocking and rescoring-based strategy with Glide SP and Glide XP, and the hitlist was initially screened by comparing their docking scores with that of reported allosteric inhibitors, myricetin and curcumin.The hitlist was subsequently screened by comparing the mol. mechanics with generalised Born and surface area solvation (MM-GBSA) energy with that of the standardsTen hits were finally selected by virtual screening, and the stability of the hit-receptor complexes was determined with 100 ns mol. dynamics (MD) simulations in an explicit solvent.Trajectory visualisation and analyses of the RMSD and RMSF values revealed that three hits, including two catechins, remained stably bound to the allosteric binding site throughout the production run.Hit-receptor interaction analyses revealed that the hits formed highly stable interactions with Glu 88, Trp 89, Leu 149, Ile 165, and Asn 167, and MM-GBSA energy anal. revealed that the three hits had high binding affinity to the allosteric site.The findings obtained herein can aid in identifying novel serotype-specific inhibitors of DENV protease in future.

2023-05-01·European Journal of Medicinal Chemistry

N-sulfonyl peptide-hybrids as a new class of dengue virus protease inhibitors

Article

作者: Kühl, Nikos ; Behrouz, Somayeh ; Klein, Christian D

Dengue virus (DENV) from the Flaviviridae family causes an epidemic disease that seriously threatens human life. The viral serine protease NS2B-NS3 is a promising target for drug development against DENV and other flaviviruses. We here report the design, synthesis, and in-vitro characterization of potent peptidic inhibitors of DENV protease with a sulfonyl moiety as N-terminal cap, thereby creating sulfonamide-peptide hybrids. The in-vitro target affinities of some synthesized compounds were in the nanomolar range, with the most promising derivative reaching a K_i value of 78 nM against DENV-2 protease. The synthesized compounds did not have relevant off-target activity nor cytotoxicity. The metabolic stability of compounds against rat liver microsomes and pancreatic enzymes was remarkable. In general, the integration of sulfonamide moieties at the N-terminus of peptidic inhibitors proved to be a promising and attractive strategy for further drug development against DENV infections.