Treatment with the Smallpox Antiviral Tecovirimat (ST-246) Alone or in Combination with ACAM2000 Vaccination Is Effective as a Postsymptomatic Therapy for Monkeypox Virus Infection

Berhanu, Aklile; Prigge, Jonathan T.; Silvera, Peter; Honeychurch, Kady M.; Hruby, Dennis E.; Grosenbach, Douglas W.

doi:10.1128/aac.00208-15

Cited by 87 publications

(68 citation statements)

References 10 publications

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“…In comparison, tecovirimat provide full protection against monkeypox either given alone or in combination with small pox vaccine after having disease of monkeypox. Moreover, when given tecovirimat 4, 5, or 6 day after infection was effective 83% for days 4 and 5 and 50% effective for day 6 (Berhanu et al, 2015).…”

Section: Need For Having An Antiviral Drug St-246mentioning

confidence: 91%

Monkeypox Transmission, Need and Treatment of Humans with an Antiviral Drug

Jabeen

Umbreen

2017

Int J Soc Sci Mgt

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Monkeypox is a viral zoonotic disease belongs to the family Poxviridae and Orthopoxvirus genus. Transmission of monkey pox is through direct contact with infected animal and blood. Human to human transmission occur through respiratory route but previously so many studies are conducted to prove that monkey pox viruse was not transmitted through the respiratory route both in animals and humans. But now monkey pox is able to survive in humans due to genetic changes and human to human transmission is possible. Because it can be used as bioweapon, So there is a great need of having an antiviral drug which is effective against monkey pox virus.ST 246 proved effective in vivo and in vitro in infected animals and trials done safely on non-infected humans but no data is available about the effectiveness of ST 246 on monkey pox or Orthopox infected human treated with ST 246.

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Section: Need For Having An Antiviral Drug St-246mentioning

confidence: 91%

Monkeypox Transmission, Need and Treatment of Humans with an Antiviral Drug

Jabeen

Umbreen

2017

Int J Soc Sci Mgt

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“…Doses between 3-300mg/kg were highly protective up to 5 days p.i. if given for a duration of 14 days; though 3mg/kg was the minimum dose, 10mg/kg also reduced viremia and lesion count (16,(98)(99)(100). As lesions appear by 1 day p.i., results suggest tecovirimat can be given post-lesionally (99).…”

Section: Intravenous Monkeypox Model (2 Studies)mentioning

confidence: 97%

“…Efficacy of tecovirimat and vaccination was assessed by 3 studies. Coadministration with ACAM2000 was tested in healthy cynomolgus macaques in an intravenous monkeypox model (100). Where ACAM2000 given alone was not efficacious, all animals treated with tecovirimat, with or without ACAM2000 were fully protected from initial challenge, and re-challenge 2 months later.…”

Section: Tecovirimatmentioning

confidence: 99%

Efficacy of three key antiviral drugs used to treat orthopoxvirus infections: a systematic review

Yu¹,

Raj²

2019

Global Biosecurity

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Background: In a global political climate increasingly concerned about terrorism, bioterrorism agents such as smallpox would undoubtedly be catastrophic. Since WHO announced the eradication of smallpox in 1980, consequently discontinuing the worldwide vaccination campaign, today's population is either immunologically naïve or has waning levels of protection. Further, up to 25% of today's population are contraindicated for smallpox vaccination due to various immunodeficiency conditions. The aim of this study was to evaluate the efficacy of the anti-DNA antivirals cidofovir (CDV), brincidofovir (BCV) and tecovirimat against smallpox and other orthopoxviruses. As of July 2018, FDA approved tecovirimat as the first treatment for smallpox. Methods: A systematic review was conducted to identify relevant literature describing the efficacy and safety of CDV, BCV and tecovirimat including in vitro and in vivo animal studies, human safety trials and human case reports of orthopoxvirus infection. Results: 158 studies met the inclusion criteria. In vitro and in vivo animal studies have found that CDV, BCV and tecovirimat are highly efficacious when used therapeutically and prophylactically. They are partially protective in moderate, but not severe, immunodeficiency models. Clinical trials consistently report BCV and tecovirimat to be safe and well tolerated in humans. In human case reports, CDV, BCV and tecovirimat contributed to recovery from orthopoxvirus infection. BCV and tecovirimat demonstrate strong synergistic effect and may reduce risk of antiviralresistant strains. Conclusion: BCV and tecovirimat are particularly promising as anti-smallpox agents. Gaps in the literature indicate that further research should focus on developing more robust immunodeficiency and antiviral-resistance models.

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“…Tecovirimat (ST-246) (SIGA) (Corvallis, OR, USA), is a small molecule inhibitor that targets the viral envelop protein F13, and prevents enveloped virus egress. This drug is efficacious in various animal models [ 116 , 121 , 133 , 134 , 135 , 136 , 137 ], and unaccepted toxicity was not reported. Yet, the risk of drug resistance following extended use exists.…”

Section: Antiviral Therapymentioning

confidence: 99%

Challenges and Achievements in Prevention and Treatment of Smallpox

2018

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Declaration of smallpox eradication by the WHO in 1980 led to discontinuation of the worldwide vaccination campaign. The increasing percentage of unvaccinated individuals, the existence of its causative infectious agent variola virus (VARV), and the recent synthetic achievements increase the threat of intentional or accidental release and reemergence of smallpox. Control of smallpox would require an emergency vaccination campaign, as no other protective measure has been approved to achieve eradication and ensure worldwide protection. Experimental data in surrogate animal models support the assumption, based on anecdotal, uncontrolled historical data, that vaccination up to 4 days postexposure confers effective protection. The long incubation period, and the uncertainty of the exposure status in the surrounding population, call for the development and evaluation of safe and effective methods enabling extension of the therapeutic window, and to reduce the disease manifestations and vaccine adverse reactions. To achieve these goals, we need to evaluate the efficacy of novel and already licensed vaccines as a sole treatment, or in conjunction with immune modulators and antiviral drugs. In this review, we address the available data, recent achievements, and open questions.

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Treatment with the Smallpox Antiviral Tecovirimat (ST-246) Alone or in Combination with ACAM2000 Vaccination Is Effective as a Postsymptomatic Therapy for Monkeypox Virus Infection

Cited by 87 publications

References 10 publications

Monkeypox Transmission, Need and Treatment of Humans with an Antiviral Drug

Monkeypox Transmission, Need and Treatment of Humans with an Antiviral Drug

Efficacy of three key antiviral drugs used to treat orthopoxvirus infections: a systematic review

Challenges and Achievements in Prevention and Treatment of Smallpox

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