New effective chemically synthesized anti-smallpox compound NIOCH-14

Mazurkov, O. Yu.; Кабанов, А. С.; Шишкина, Л. Н.; Сергеев, А. А.; Скарнович, М. О.; Бормотов, Н. И.; Ovchinnikova, A. S.; Titova, K. A.; Galahova, D. O.; Le, Bulychev; Sergeev, Artemiy A.; Taranov, Oleg S.; Selivanov, B. A.; Tikhonov, А. Ya.; Zavjalov, Evgenii L.; Агафонов, А. П.

doi:10.1099/jgv.0.000422

Cited by 61 publications

(55 citation statements)

References 37 publications

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“…A prophylactic regimen of 40mg/kg starting 1 day prior to infection, followed by doses 2 hours prior infection and daily for 6 days p.i. was 100% protective (97).…”

Section: Intranasal Monkeypox Model (3 Studies)mentioning

confidence: 96%

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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“…A prophylactic regimen of 40mg/kg starting 1 day prior to infection, followed by doses 2 hours prior infection and daily for 6 days p.i. was 100% protective (97).…”

Section: Intranasal Monkeypox Model (3 Studies)mentioning

confidence: 96%

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

Yu¹,

Raj²

2019

Global Biosecurity

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“…Statistical treatment of results was carried out with standard methods using the software package Statistica 6.0 (StatSoft, Tulsa, OK, USA), with assessment of significant differences (p < 0.05) for a 95% confidence level [18].…”

Section: Statisticsmentioning

confidence: 99%

Effect of the Route of Administration of the Vaccinia Virus Strain LIVP to Mice on Its Virulence and Immunogenicity

Щелкунов

Yakubitskiy

Сергеев

et al. 2020

Viruses

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The mass smallpox vaccination campaign has played a crucial role in smallpox eradication. Various strains of the vaccinia virus (VACV) were used as a live smallpox vaccine in different countries, their origin being unknown in most cases. The VACV strains differ in terms of pathogenicity exhibited upon inoculation of laboratory animals and reactogenicity exhibited upon vaccination of humans. Therefore, each generated strain or clonal variant of VACV needs to be thoroughly studied in in vivo systems. The clonal variant 14 of LIVP strain (LIVP-14) was the study object in this work. A comparative analysis of the virulence and immunogenicity of LIVP-14 inoculated intranasally (i.n.), intradermally (i.d.), or subcutaneously (s.c.) to BALB/c mice at doses of 108, 107, and 106 pfu was carried out. Adult mice exhibited the highest sensitivity to the i.n. administered LIVP-14 strain, although the infection was not lethal. The i.n. inoculated LIVP-14 replicated efficiently in the lungs. Furthermore, this virus was accumulated in the brain at relatively high concentrations. Significantly lower levels of LIVP-14 were detected in the liver, kidneys, and spleen of experimental animals. No clinical manifestations of the disease were observed after i.d. or s.c. injection of LIVP-14 to mice. After s.c. inoculation, the virus was detected only at the injection site, while it could disseminate to the liver and lungs when delivered via i.d. administration. A comparative analysis of the production of virus-specific antibodies by ELISA and PRNT revealed that the highest level of antibodies was induced in i.n. inoculated mice; a lower level of antibodies was observed after i.d. administration of the virus and the lowest level after s.c. injection. Even at the lowest studied dose (106 pfu), i.n. or i.d. administered LIVP-14 completely protected mice against infection with the cowpox virus at the lethal dose. Our findings imply that, according to the ratio between such characteristics as pathogenicity/immunogenicity/protectivity, i.d. injection is the optimal method of inoculation with the VACV LIVP-14 strain to ensure the safe formation of immune defense after vaccination against orthopoxviral infections.

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“…This compound is currently undergoing clinical trials. NIOCH-14, an analog of ST-246, also showed high activity in different animal models of orthopoxvirus infections [ 93 ].…”

Section: Anti-smallpox Chemotherapeuticsmentioning

confidence: 99%

40 Years without Smallpox

Shchelkunova¹,

Щелкунов²

2017

Acta Naturae

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The last case of natural smallpox was recorded in October, 1977. It took humanity almost 20 years to achieve that feat after the World Health Organization had approved the global smallpox eradication program. Vaccination against smallpox was abolished, and, during the past 40 years, the human population has managed to lose immunity not only to smallpox, but to other zoonotic orthopoxvirus infections as well. As a result, multiple outbreaks of orthopoxvirus infections in humans in several continents have been reported over the past decades. The threat of smallpox reemergence as a result of evolutionary transformations of these zoonotic orthopoxviruses exists. Modern techniques for the diagnostics, prevention, and therapy of smallpox and other orthopoxvirus infections are being developed today.

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New effective chemically synthesized anti-smallpox compound NIOCH-14

Cited by 61 publications

References 37 publications

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

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

Effect of the Route of Administration of the Vaccinia Virus Strain LIVP to Mice on Its Virulence and Immunogenicity

40 Years without Smallpox

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