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The Smallpox Story
Published in Rae-Ellen W. Kavey, Allison B. Kavey, Viral Pandemics, 2020
Rae-Ellen W. Kavey, Allison B. Kavey
After 9/11, the subject of treatment for smallpox was revisited. Animal studies suggested that the antiviral drug cidofovir might be a useful therapeutic agent. Cidofovir was the first nucleotide analogue approved for clinical use and has demonstrated in vitro activity against poxviruses; its clinical utility is unknown. It is given intravenously with careful monitoring of kidney function. Specific application in smallpox infection has not been investigated.87 The US government has stockpiled 2 million doses of the antiviral medication Arestvyr, an egress inhibitor which prevents the formation of extracellular enveloped forms of orthopoxviruses, to be used in exposed individuals in combination with the smallpox vaccine in the event of a smallpox bioterrorist attack. Tecovirimat is an oral antiviral drug for orthopox viruses which inhibits the function of a major envelope protein required for the production of extracellular virus.88,89 Theoretically, it could be combined with smallpox vaccine to maximize disease suppression after exposure to the virus. For obvious reasons, it has never been tested in humans, but more than 90% of monkeys and rabbits that were infected with a virus similar to smallpox and then given the drug survived. In August of 2018, the FDA approved TPOXX, a commercially developed version of tecovirimat to treat smallpox. TPOXX has now been added to the American emergency stockpile for biodefense against smallpox, with 2 million doses delivered to the US government to be added to the stockpile as part of the emergency biodefense reserve.89
Potential therapeutic targets for Mpox: the evidence to date
Published in Expert Opinion on Therapeutic Targets, 2023
Siddappa N Byrareddy, Kalicharan Sharma, Shrikesh Sachdev, Athreya S. Reddy, Arpan Acharya, Kaylee M. Klaustermeier, Christian L Lorson, Kamal Singh
Tecovirimat (ST-240) targets viral phospholipase protein (p37 or C19L od MPXV). It was discovered by high throughput screening against smallpox [132]. Tecovirimat inhibits the biogenesis of the MV to EV. However, the MV could still be released through cell lysis. In effect, Tecovirimat inhibits only a sub-population of the poxviruses. Thus, Tecovirimat helps to prevent viral spread and reduces viremia [132]. Limited studies have shown that Tecovirimat can be safely used after smallpox vaccination [97] and has synergistic effect with BCV [86]. Since Tecovirimat inhibits p37 and remains a promising anti-MPX drug, medicinal chemistry efforts to develop analogs of Tecovirimat have been limited. The absence of a solved structure of p37 remains the bottleneck in developing more potent drugs that target this protein. Tecovirimat has been shown to be well tolerated among 359 patients who received this drug in a Phase III clinical trial [92].
Monkeypox: a new face of outbreak
Published in Expert Review of Vaccines, 2022
Vivek P. Chavda, Lalitkumar K. Vora, Vasso Apostolopoulos
It is feared that the monkeypox virus might evolve into a more potent human infection. Perhaps this is due to the genetic composition of the virus, anthropogenic factors, variations in host behavior, and the fact that smallpox vaccination is no longer administered due to the elimination of the variola virus [27]. In this regard, anyone born post 1980 are not vaccinated and are at risk of disease. Moreover, real-time polymerase chain reaction (PCR) experiments have been utilized to identify two genes targeted by the monkeypox virus [28]. A test for immunoglobulin M (IgM) antibodies was conducted since anti-vaccine IgM antibodies from earlier smallpox immunizations should not be detected [29]. Diagnostic tests may also concentrate on cellular immune responses to certain infections. Counting orthopoxvirus-specific T cells is one such approach that is now under investigation [30]. While primates, including monkeys, are susceptible to infection, it is believed that squirrels and other rodents serve as reservoir hosts for the virus. Further spread of this orthopox virus must be carefully contained and not allow novel (variant) viruses to adapt further to the human population (Figure 2). Tecorivimat is a recently approved antiviral medicine for orthopoxvirus-associated illnesses, including monkeypox, based on animal models and human evidence for safety, bioavailability, and therapeutic efficacy [31,32]. Tecovirimat did not cause side effects and appeared to lead to a decrease in viral levels and a speedier recovery. Based on comparable results, the FDA authorized a second smallpox medication, brincidofovir, in 2021.
Mpox: epidemiology, clinical manifestations and recent developments in treatment and prevention
Published in Expert Review of Anti-infective Therapy, 2023
Nikil Selvaraj, Shreya Shyam, Puvin Dhurairaj, Kaviarasan Thiruselvan, Akil Thiruselvan, Yochana Kancherla, Pritika Kandamaran
Regarding MPXV infections specifically, tecovirimat was used to treat a patient in the United States in 2021 who had Mpox due to travel [5]. Five hundred courses of tecovirimat were slated to be used to treat Mpox in the Central African Republic as part of an extended access protocol that was announced in July 2021. One of seven patients got tecovirimat for two weeks in the recent case study by Adler et al. The patient’s sickness and virus shedding times were shorter, and they had no negative consequences. Recently, one patient treated with tecovirimat was listed in the CDC report on the initial 17 individuals with MPXV infection who were verified to have been infected in the US during the ongoing 2022 outbreak [21].