Validation of Babesia proteasome as a drug target

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60076658%3A12310%2F18%3A43897427" target="_blank" >RIV/60076658:12310/18:43897427 - isvavai.cz</a>

Alternative codes found

RIV/60077344:_____/18:00498709

Result on the web

<a href="https://reader.elsevier.com/reader/sd/pii/S2211320717301574?token=4498D51CE0BA52164913AEB4E75E32F895392D8B4C279664C354B316B296233188A065D726B216370D8BA055E3D89770" target="_blank" >https://reader.elsevier.com/reader/sd/pii/S2211320717301574?token=4498D51CE0BA52164913AEB4E75E32F895392D8B4C279664C354B316B296233188A065D726B216370D8BA055E3D89770</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ijpddr.2018.08.001" target="_blank" >10.1016/j.ijpddr.2018.08.001</a>

Result language

angličtina

Original language name

Validation of Babesia proteasome as a drug target

Original language description

Babesiosis is a tick-transmitted zoonosis caused by apicomplexan parasites of the genus Babesia. Treatment of this emerging malaria-related disease has relied on antimalarial drugs and antibiotics. The proteasome of Plasmodium, the causative agent of malaria, has recently been validated as a target for anti-malarial drug development and therefore, in this study, we investigated the effect of epoxyketone (carfilzomib, ONX-0914 and epoxomicin) and boronic acid (bortezomib and ixazomib) proteasome inhibitors on the growth and survival of Babesia. Testing the compounds against Babesia divergens ex vivo revealed suppressive effects on parasite growth with activity that was higher than the cytotoxic effects on a non-transformed mouse macrophage cell line. Furthermore, we showed that the most-effective compound, carfilzomib, significantly reduces parasite multiplication in a Babesia microti infected mouse model without noticeable adverse effects. In addition, treatment with carfilzomib lead to an ex vivo and in vivo decrease in proteasome activity and accumulation of polyubiquitinated proteins compared to untreated control. Overall, our results demonstrate that the Babesia proteasome is a valid target for drug development and warrants the design of potent and selective B. divergens proteasome inhibitors for the treatment of babesiosis.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30310 - Parasitology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

International Journal for Parasitology: Drugs and Drug Resistance

ISSN

2211-3207

e-ISSN

—

Volume of the periodical

8

Issue of the periodical within the volume

3

Country of publishing house

GB - UNITED KINGDOM

Number of pages

9

Pages from-to

394-402

UT code for WoS article

000452063600005

EID of the result in the Scopus database

2-s2.0-85051269921