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Antiviral research

Antiviral research

IF: 4.5
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Identification of a clinical compound losmapimod that blocks Lassa virus entry

Published:1 July 2019 DOI: 10.1016/j.antiviral.2019.03.014 PMID: 30953674
Xiaoyu Zhang , Feihu Yan , Ke Tang , Qing Chen , Jiamei Guo , Wenjun Zhu , Shihua He , Logan Banadyga , Xiangguo Qiu , Ying Guo

Abstract

Lassa virus (LASV) causes Lassa hemorrhagic fever in humans and poses a significant threat to public health in West Africa. Current therapeutic treatments for Lassa fever are limited, making the development of novel countermeasures an urgent priority. In this study, we identified losmapimod, a p38 mitogen-activated protein kinase (MAPK) inhibitor, from 102 screened compounds as an inhibitor of LASV infection. Losmapimod exerted its inhibitory effect against LASV after p38 MAPK down-regulation, and, interestingly, had no effect on other arenaviruses capable of causing viral hemorrhagic fever. Mechanistic studies showed that losmapimod inhibited LASV entry by affecting the stable signal peptide (SSP)-GP2 subunit interface of the LASV glycoprotein, thereby blocking pH-dependent viral fusion. As an aryl heteroaryl bis-carboxyamide derivative, losmapimod represents a novel chemical scaffold with anti-LASV activity, and it provides a new lead structure for the future development of LASV fusion inhibitors.

Substances (8)

Materials
Procduct Name CAS Molecular Formula Supplier Price
DESIPRAMINE HYDROCHLORIDE 58-28-6 C18H23ClN2 184 suppliers $21.00-$1972.00
DESIPRAMINE HYDROCHLORIDE 58-28-6 C18H23ClN2 184 suppliers $21.00-$1972.00
DESIPRAMINE HYDROCHLORIDE 58-28-6 C18H23ClN2 184 suppliers $21.00-$1972.00
DESIPRAMINE HYDROCHLORIDE 58-28-6 C18H23ClN2 184 suppliers $21.00-$1972.00
Losmapimod (GW856553X) 585543-15-3 C22H26FN3O2 121 suppliers $10.00-$1300.00
Losmapimod (GW856553X) 585543-15-3 C22H26FN3O2 121 suppliers $10.00-$1300.00
Losmapimod (GW856553X) 585543-15-3 C22H26FN3O2 121 suppliers $10.00-$1300.00
Losmapimod (GW856553X) 585543-15-3 C22H26FN3O2 121 suppliers $10.00-$1300.00

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