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. 2015 Dec;96(12):3484-3492.
doi: 10.1099/jgv.0.000309.

Chloroquine inhibited Ebola virus replication in vitro but failed to protect against infection and disease in the in vivo guinea pig model

Stuart D Dowall  1 , Andrew Bosworth  1 , Robert Watson  1 , Kevin Bewley  1 , Irene Taylor  1 , Emma Rayner  1 , Laura Hunter  1 , Geoff Pearson  1 , Linda Easterbrook  1 , James Pitman  1 , Roger Hewson  1 , Miles W Carroll  1
Affiliations

Chloroquine inhibited Ebola virus replication in vitro but failed to protect against infection and disease in the in vivo guinea pig model

Stuart D Dowall et al. J Gen Virol. 2015 Dec.

Abstract

Ebola virus (EBOV) is highly pathogenic, with a predisposition to cause outbreaks in human populations accompanied by significant mortality. Owing to the lack of approved therapies, screening programmes of potentially efficacious drugs have been undertaken. One of these studies has demonstrated the possible utility of chloroquine against EBOV using pseudotyped assays. In mouse models of EBOV disease there are conflicting reports of the therapeutic effects of chloroquine. There are currently no reports of its efficacy using the larger and more stringent guinea pig model of infection. In this study we have shown that replication of live EBOV is impaired by chloroquine in vitro. However, no protective effects were observed in vivo when EBOV-infected guinea pigs were treated with chloroquine. These results advocate that chloroquine should not be considered as a treatment strategy for EBOV.

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Figures

Fig. 1.
Fig. 1.
Survival and clinical signs of EBOV-challenged guinea pigs treated with oral chloroquine compared with untreated animals. (a) Survival analysis between chloroquine-treated animals and untreated animals. (b) Weight changes showing percentage difference compared with the day of challenge. (c) Temperature difference in animals compared with baseline taken on the day of challenge. (d) Clinical score of animals post-challenge. (b–d) Mean results are shown of animals still surviving in all groups, with error bars denoting se. Group sizes of six guinea pigs were used.
Fig. 2.
Fig. 2.
Viral RNA levels in blood in EBOV-challenged guinea pigs treated with chloroquine compared with untreated controls. (a) Samples taken at day 8 post-challenge. Means values are plotted with the error bar denoting se. (b) Samples taken at the time of necropsy, when animals met humane clinical end points, except for animal 98 583, which was culled at the scheduled end of the study on day 18 post-challenge.
Fig. 3.
Fig. 3.
EBOV antigen staining in the spleen and liver of EBOV-challenged guinea pigs treated with chloroquine or untreated. (a, b) Spleen. (a) Chloroquine-treated guinea pig, ID 98562. Scattered cells positive for viral antigen in both red and white pulp, predominantly in the former. Inset, higher magnification image ( × 227). (b) Untreated guinea pig, ID 89185. Scattered cells positive for viral antigen in both red and white pulp, predominantly in the former. Inset, higher magnification image ( × 227). (c, d) Liver. (c) Chloroquine-treated guinea pig, ID 98604. Multiple foci with strong staining for viral antigen. Inset, higher magnification ( × 227) of a focal lesion. (d) Untreated, ID 98609. Multiple foci with strong staining for viral antigen. Inset, higher magnification ( × 227) of a focal lesion. Immunohistochemistry: anti-EBOV VP40 antibody and counterstained with haematoxylin.
See this image and copyright information in PMC

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