Potential anti-monkeypox virus activity of atovaquone, mefloquine, and molnupiravir, and their potential use as treatments

Akazawa, Daisuke; Ohashi, Hirofumi; Hishiki, Takayuki; Morita, Takeshi; Iwanami, Shoya; Kim, Kwang Su; Jeong, Yong Dam; Park, Eun-Sil; Kataoka, Michiyo; Shionoya, Kaho; Mifune, Junki; Tsuchimoto, Kana; Ojima, Shinjiro; Azam, Aa Haeruman; Nakajima, Sachiko; Park, Hyeongki; Yoshikawa, Tomoki; Shimojima, Masayuki; Kiga, Kotaro; Iwami, Shingo; Maeda, Ken; Suzuki, Tadaki; Ebihara, Hideki; Takahashi, Yoshimasa; Watashi, Koichi

doi:10.1101/2022.08.02.502485

Cited by 12 publications

(5 citation statements)

References 48 publications

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“…In a study, Atovaquone was used in conjunction with other recognized antiorthopoxvirus medications such as tecovirimat. It is worth noting that the combination of tecovirimat and atovaquone reduced the levels of MPXV DNA in cell culture tests while having no negative effects on the cells themselves 161 …”

Section: Monkeypox Therapeutic Drug Targets and Strategiesmentioning

confidence: 96%

“…According to a study, the levels of intracellular MPXV DNA were decreased by atovaquone, leflunomide, and teriflunomide (DHODH inhibitors) in a dose‐dependent manner. It was demonstrated that inhibiting DHODH prevented the reproduction of the MPXV 161 …”

Section: Monkeypox Therapeutic Drug Targets and Strategiesmentioning

confidence: 99%

“…It is worth noting that the combination of tecovirimat and atovaquone reduced the levels of MPXV DNA in cell culture tests while having no negative effects on the cells themselves. 161…”

Section: Combination Therapymentioning

confidence: 99%

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Monkeypox outbreak 2022: What we know so far and its potential drug targets and management strategies

Rabaan

Abas

Tallei

et al. 2022

Journal of Medical Virology

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Monkeypox is a rare zoonotic disease caused by infection with the monkeypox virus. The disease can result in flu‐like symptoms, fever, and a persistent rash. The disease is currently spreading throughout the world and prevention and treatment efforts are being intensified. Although there is no treatment that has been specifically approved for monkeypox virus infection, infected patients may benefit from using certain antiviral medications that are typically prescribed for the treatment of smallpox. The drugs are tecovirimat, brincidofovir, and cidofovir, all of which are currently in short supply due to the spread of the monkeypox virus. Resistance is also a concern, as widespread replication of the monkeypox virus can lead to mutations that produce monkeypox viruses that are resistant to the currently available treatments. This article discusses monkeypox disease, potential drug targets, and management strategies to overcome monkeypox disease. With the discovery of new drugs, it is hoped that the problem of insufficient drugs will be resolved, and it is not anticipated that drug resistance will become a major issue in the near future.

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Section: Monkeypox Therapeutic Drug Targets and Strategiesmentioning

confidence: 96%

Section: Monkeypox Therapeutic Drug Targets and Strategiesmentioning

confidence: 99%

See 1 more Smart Citation

Monkeypox outbreak 2022: What we know so far and its potential drug targets and management strategies

Rabaan

Abas

Tallei

et al. 2022

Journal of Medical Virology

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“…An in vitro screen of 132 clinically approved drugs identified atovaquone, mefloquine, and molnupiravir with efficacy against MPXV. 52 Supportiveandsymptomaticcare,whichmaybetheonlyresources availableforpatientsinresource-limitedsettings,playanimportantrole in the management of monkeypox. Pain management is key and requires topical agents, oral medications, or nerve blocks.…”

Section: Managementmentioning

confidence: 99%

Neurologic Complications of Smallpox and Monkeypox

et al. 2022

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ImportanceOrthopox viruses include smallpox virus, a once feared but now eradicated virus, as well as monkeypox virus. Monkeypox is an emerging virus initially isolated in 1958, previously unrecognized outside sub-Saharan Africa until a worldwide outbreak in May 2022. It is important to review known neurologic consequences of both these viruses, as complications of smallpox may be relevant to monkeypox, though complications of monkeypox may be rarer and perhaps less severe.ObservationsThis was a literature review of the known neurologic complications of smallpox, which include encephalitis, transverse myelitis, and acute disseminated encephalomyelitis among others; historical complications of smallpox vaccination, including postvaccinal encephalomyelitis; and the known neurologic complications of monkeypox, which include headaches and mood disturbances, as well as rare presentations of encephalitis, transverse myelitis, and seizures. Of concern is the possibility of viral persistence and systemic complications in immunocompromised individuals. Also provided were considerations for diagnosis, current treatment, and prevention of monkeypox.Conclusions and RelevanceMonkeypox should be considered in high-risk populations who present with neurologic syndromes. Diagnosis may require serology and polymerase chain reaction testing of blood and spinal fluid. Antiviral therapy should be initiated early in the course of the illness.

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“…An in silico study has shown better efficacy against mpox virus with combination of atovaquone and TPOXX (Akazawa et al, 2022). Some of the common associated adverse events are headaches, gastrointestinal disturbances, and injection site complaints like pain, swelling, erythema and extravasation (De Clercq et al, 2022;Food and Drug Administration, 2022;Siegrist and Sassine, 2022).…”

Section: Treatments and Vaccinesmentioning

confidence: 99%

Pharmacological treatment and vaccines in monkeypox virus: a narrative review and bibliometric analysis

et al. 2023

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Mpox (earlier known as monkeypox) virus infection is a recognized public health emergency. There has been little research on the treatment options. This article reviews the specific drugs used to treat mpox virus infection and the vaccines used here. Instead of focusing on the mechanistic basis, this review narrates the practical, real-life experiences of individual patients of mpox virus disease being administered these medicines. We conducted a bibliometric analysis on the treatment of the mpox virus using data from several databases like PubMed, Scopus, and Embase. The research on this topic has grown tremendously recently but it is highly concentrated in a few countries. Cidofovir is the most studied drug. This is because it is indicated and also used off-label for several conditions. The drugs used for mpox virus infection include tecovirimat, cidofovir, brincidofovir, vaccinia immune globulin, and trifluridine. Tecovirimat is used most frequently. It is a promising option in progressive mpox disease in terms of both efficacy and safety. Brincidofovir has been associated with treatment discontinuation due to elevated hepatic enzymes. Cidofovir is also not the preferred drug, often used because of the unavailability of tecovirimat. Trifluridine is used topically as an add-on agent along with tecovirimat for ocular manifestations of mpox virus disease. No study reports individual patient data for vaccinia immune globulin. Though no vaccine is currently approved for mpox virus infection, ACAM 2000 and JYNNEOS are the vaccines being mainly considered. ACAM 2000 is capable of replicating and may cause severe adverse reactions. It is used when JYNNEOS is contraindicated. Several drugs and vaccines are under development and have been discussed alongside pragmatic aspects of mpox virus treatment and prevention. Further studies can provide more insight into the safety and efficacy of Tecovirimat in actively progressing mpox virus disease.

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Potential anti-monkeypox virus activity of atovaquone, mefloquine, and molnupiravir, and their potential use as treatments

Cited by 12 publications

References 48 publications

Monkeypox outbreak 2022: What we know so far and its potential drug targets and management strategies

Monkeypox outbreak 2022: What we know so far and its potential drug targets and management strategies

Neurologic Complications of Smallpox and Monkeypox

Pharmacological treatment and vaccines in monkeypox virus: a narrative review and bibliometric analysis

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