The antimalarial drug amodiaquine possesses anti‐ZIKA virus activities

Han, Ying-Shan; Mésplède, Thibault; Xu, Hongtao; Quan, Yudong; Wainberg, Mark A.

doi:10.1002/jmv.25031

Cited by 43 publications

(41 citation statements)

References 41 publications

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“…Aminoquinolines were proposed for the treatment of other viral infections, such as ZIKV. In 2017, it was demonstrated that CQ and AQ exerted anti-ZIKV activity in Vero cells, with low micromolar IC 50 s [140]. These results were in agreement with the decreasing number of ZIKV-infected cells after CQ treatment.…”

Section: Chloroquine and Hydroxychloroquine And Emerging Virusesmentioning

confidence: 62%

“…Flaviviridae BVDV(surrogate HCV) Artemisinin in vitro [187,188] Dihydroartemisinin in vitro [63] HCV Artemisinin in vitro [20][21][22] Artesunate in vitro [57] Chloroquine in vitro [148][149][150] ZIKV Mefloquine in vitro [130,131] Chloroquine in vitro [140,141] Amodiaquine in vitro [140] Atovaquone in vitro [166] DENV Quinine sulfate in vitro [66] Mefloquine in vitro [131] Halofantrine in vitro [134] Doxycycline in vitro [168,178] Amodiaquine in vitro [162] CHIKV Doxycycline in vitro [169] Chloroquine in vitro [37,138,139] Atovaquone in vitro [166] Togaviridae SFV Halofantrine in vitro [134] Rhabdoviridae VSV Doxycycline in vitro [170] Orthomyxoviridae IAV Quinine sulfate in vitro [70] In vivo (mouse) [67] Mefloquine in vitro [70] Doxycycline in vivo (mouse) [171] Chloroquine in vitro [159]…”

Section: Virus Family Virus Species Drug Type Of Study (Model) Referementioning

confidence: 99%

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The Use of Antimalarial Drugs against Viral Infection

et al. 2020

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In recent decades, drugs used to treat malaria infection have been shown to be beneficial for many other diseases, including viral infections. In particular, they have received special attention due to the lack of effective antiviral drugs against new emerging viruses (i.e., HIV, dengue virus, chikungunya virus, Ebola virus, etc.) or against classic infections due to drug-resistant viral strains (i.e., human cytomegalovirus). Here, we reviewed the in vitro/in vivo and clinical studies conducted to evaluate the antiviral activities of four classes of antimalarial drugs: Artemisinin derivatives, aryl-aminoalcohols, aminoquinolines, and antimicrobial drugs.

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Section: Chloroquine and Hydroxychloroquine And Emerging Virusesmentioning

confidence: 62%

Section: Virus Family Virus Species Drug Type Of Study (Model) Referementioning

confidence: 99%

The Use of Antimalarial Drugs against Viral Infection

et al. 2020

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“…Despite current potential protection due to herd and selfimmunity, environmental factors, and host-vector-virus interactions that keep ZIKV at low incidence (1,55,56), preventing ZIKV and other arbovirus infections should be a priority. In recent years, many compounds have been proposed as potential anti-ZIKV agents following in vitro results (29,30,(57)(58)(59)(60)(61)(62)(63)(64)(65)(66). Some of these drugs have an extensive background in the medical field and offer attractive options, either alone or in combination, for treatment and perhaps prophylaxis of ZIKV infections; however, most of them remain inadequate to be used during pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Atovaquone Inhibits Arbovirus Replication through the Depletion of Intracellular Nucleotides

Kottkamp

Jesus

Grande

et al. 2019

J Virol

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Arthropod-borne viruses represent a significant public health threat worldwide, yet there are few antiviral therapies or prophylaxes targeting these pathogens. In particular, the development of novel antivirals for high-risk populations such as pregnant women is essential to prevent devastating disease such as that which was experienced with the recent outbreak of Zika virus (ZIKV) in the Americas. One potential avenue to identify new and pregnancy-acceptable antiviral compounds is to repurpose well-known and widely used FDA-approved drugs. In this study, we addressed the antiviral role of atovaquone, an FDA Pregnancy Category C drug and pyrimidine biosynthesis inhibitor used for the prevention and treatment of parasitic infections. We found that atovaquone was able to inhibit ZIKV and chikungunya virus virion production in human cells and that this antiviral effect occurred early during infection at the initial steps of viral RNA replication. Moreover, we were able to complement viral replication and virion production with the addition of exogenous pyrimidine nucleosides, indicating that atovaquone functions through the inhibition of the pyrimidine biosynthesis pathway to inhibit viral replication. Finally, using an ex vivo human placental tissue model, we found that atovaquone could limit ZIKV infection in a dose-dependent manner, providing evidence that atovaquone may function as an antiviral in humans. Taken together, these studies suggest that atovaquone could be a broad-spectrum antiviral drug and a potential attractive candidate for the prophylaxis or treatment of arbovirus infection in vulnerable populations, such as pregnant women and children.IMPORTANCE The ability to protect vulnerable populations such as pregnant women and children from Zika virus and other arbovirus infections is essential to preventing the devastating complications induced by these viruses. One class of antiviral therapies may lie in known pregnancy-acceptable drugs that have the potential to mitigate arbovirus infections and disease, yet this has not been explored in detail. In this study, we show that the common antiparasitic drug atovaquone inhibits arbovirus replication through intracellular nucleotide depletion and can impair ZIKV infection in an ex vivo human placental explant model. Our study provides a novel function for atovaquone and highlights that the rediscovery of pregnancy-acceptable drugs with potential antiviral effects can be the key to better addressing the immediate need for treating viral infections and preventing potential birth complications and future disease.

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“…Despite current potential protection from herd and self-immunity, environmental factors, and host-vector-virus interactions that keep ZIKV in the low incidence figures [1], [52], [53], [54], [55], preventing ZIKV and other arbovirus infections should be a priority. In recent years, many compounds have been proposed as potential anti-ZIKV agents following in vitro results [24], [25], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65]. Some of these drugs have an extensive background in the medical field and offer attractive options, either alone or in combination, for treatment and perhaps prophylaxis of ZIKV infections; however, most of them remain inadequate to be used during pregnancy.…”

Section: Discussionmentioning

confidence: 99%

The antiparasitic drug atovaquone inhibits arbovirus replication through the depletion of intracellular nucleotides.

Kottkamp

Jesus

Grande

et al. 2018

Preprint

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Arthropod-borne viruses represent a significant public health threat worldwide yet there are few antiviral therapies or prophylaxis targeting these pathogens. In particular, the development of novel antivirals for high-risk populations such as pregnant women is essential to prevent devastating disease such as that which was experienced with the recent outbreak of Zika virus (ZIKV) in the Americas. One potential avenue to identify new and pregnancy friendly antiviral compounds is to repurpose well-known and widely used FDA approved drugs. In this study, we addressed the antiviral role of atovaquone, a FDA Pregnancy Category C drug and pyrimidine biosynthesis inhibitor used for the prevention and treatment of parasitic infections. We found that atovaquone was able to inhibit ZIKV and chikungunya virus virion production in human cells and that this antiviral effect occurred early during infection at the initial steps of viral RNA replication. Moreover, we were able to complement viral replication and virion production with the addition of exogenous pyrimidine nucleosides indicating that atovaquone is functioning through the inhibition of the pyrimidine biosynthesis pathway to inhibit viral replication. Finally, using an ex vivo human placental tissue model, we found that atovaquone could limit ZIKV infection in a dose-dependent manner providing evidence that atovaquone may function as an antiviral in humans. Taken together, these studies suggest that atovaquone could be a broad-spectrum antiviral drug and a potential attractive candidate for the prophylaxis or treatment of arbovirus infection in vulnerable populations, such as pregnant women.

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The antimalarial drug amodiaquine possesses anti‐ZIKA virus activities

Cited by 43 publications

References 41 publications

The Use of Antimalarial Drugs against Viral Infection

The Use of Antimalarial Drugs against Viral Infection

Atovaquone Inhibits Arbovirus Replication through the Depletion of Intracellular Nucleotides

The antiparasitic drug atovaquone inhibits arbovirus replication through the depletion of intracellular nucleotides.

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