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

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.

Minimal In Vivo Efficacy of Iminosugars in a Lethal Ebola Virus Guinea Pig Model

“…The difference in efficacy of iminosugars in EBOV-infected mouse and guinea pig models may be due to differences between species, EBOV-strains used or the potency of the different iminosugars, and cannot be determined without performing direct comparisons. Discrepancies in efficacy testing chloroquine against EBOV have been reported previously with efficacy observed in mice [55] but not when tested in guinea pigs [56] or hamsters [57]. The different effects on the pseudotyped virus could similarly be explained by use of GP from different EBOV-isolates and it is worth noting that, in Chang et al .…”

Repurposed Therapeutic Agents Targeting the Ebola Virus: A Systematic Review

“…This resulted in 11 drug screening,23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33 17 preclinical studies,34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50 and 9 clinical studies 51, 52, 53, 54, 55, 56, 57, 58, 59…”

“…If unavailable, we reported the half maximal inhibitory concentration or EC 50 values from the World Health Organization categorization and prioritization table 60 . A total of 14 studies included experiments on animals 26, 27, 29, 39, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50. Three of these trials were carried out on monkey species,39, 44, 50 such as the rhesus macaques, whilst the remaining 11 studies where carried on small animal models, such as mice, hamsters, or guinea pigs.…”

“…This is believed to take place by inhibiting various factors such as vesicle sorting and endosome-membrane fusion, as well as increasing endosomal pH 27 . Chloroquine was shown to successfully inhibit the Ebola virus in vitro in different studies and with various cell lines 27, 36, 39, 46. Animal studies, on the other hand, revealed mixed results.…”

Antiviral Agents Against Ebola Virus Infection: Repositioning Old Drugs and Finding Novel Small Molecules

“…2), a very well-known remedy in Traditional Chinese Medicine (TCM) for the treatment of a number of diseases such as tuberculosis, dysentery, malaria, cancer, and fever, 19 isolated from different species of plants from the Menispermaceae family, was shown to inhibit EBOV entry into host cells and infection of human macrophages (EC 50 ¼ 55 nM) by binding to TPC. [22][23][24] 20 Madrid et al showed that the antimalarial chloroquine (CQ) (Fig.…”