“…NIOCH-14 is a newly developed compound of tecovirimat analogue synthesized by the State Research Center of Virology and Biotechnology, Russia. This orally bioavailable compound demonstrated comparable results with tecovirimat studies in vitro, thus providing a promising candidate for the newer generation of anti-orthopoxvirus drugs [ 113 ].…”
The 2022 multi-country monkeypox outbreak in humans has brought new public health adversity on top of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The disease has spread to 104 countries throughout six continents of the world, with the highest burden in North America and Europe. The etiologic agent, monkeypox virus (MPXV), has been known since 1959 after isolation from infected monkeys, and virulence among humans has been reported since the 1970s, mainly in endemic countries in West and Central Africa. However, the disease has re-emerged in 2022 at an unprecedented pace, with particular concern on its human-to-human transmissibility and community spread in non-endemic regions. As a mitigation effort, healthcare workers, public health policymakers, and the general public worldwide need to be well-informed on this relatively neglected viral disease. Here, we provide a comprehensive and up-to-date overview of monkeypox, including the following aspects: epidemiology, etiology, pathogenesis, clinical features, diagnosis, and management. In addition, the current review discusses the preventive and control measures, the latest vaccine developments, and the future research areas in this re-emerging viral disease that was declared as a public health emergency of international concern.
“…NIOCH-14 is a newly developed compound of tecovirimat analogue synthesized by the State Research Center of Virology and Biotechnology, Russia. This orally bioavailable compound demonstrated comparable results with tecovirimat studies in vitro, thus providing a promising candidate for the newer generation of anti-orthopoxvirus drugs [ 113 ].…”
The 2022 multi-country monkeypox outbreak in humans has brought new public health adversity on top of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The disease has spread to 104 countries throughout six continents of the world, with the highest burden in North America and Europe. The etiologic agent, monkeypox virus (MPXV), has been known since 1959 after isolation from infected monkeys, and virulence among humans has been reported since the 1970s, mainly in endemic countries in West and Central Africa. However, the disease has re-emerged in 2022 at an unprecedented pace, with particular concern on its human-to-human transmissibility and community spread in non-endemic regions. As a mitigation effort, healthcare workers, public health policymakers, and the general public worldwide need to be well-informed on this relatively neglected viral disease. Here, we provide a comprehensive and up-to-date overview of monkeypox, including the following aspects: epidemiology, etiology, pathogenesis, clinical features, diagnosis, and management. In addition, the current review discusses the preventive and control measures, the latest vaccine developments, and the future research areas in this re-emerging viral disease that was declared as a public health emergency of international concern.
“…It should be noted that there are only three drugs approved for the treatment of the diseases caused by orthopoxviruses: they are Cidofovir, Brincidofovir and Tecovirimat (ST-246) 14 , 15 , 16 , 17 ( Figure 1 ). Following the successful preclinical trials, clinical trials of the fourth effective and bioavailable anti-smallpox compound NIOCH-14 are currently being carried out in Russia 18 , 19 . Figure 1 Structures of the compounds possessing anti-orthopoxvirus activity.…”
Section: Introductionmentioning
confidence: 99%
“…Due to the likeliness of the structures of the most effective antivirals against orthopoxviruses (Tecovirimat and NIOCH-14) and to the fact that in mammal organism NIOCH-14 transforms into ST-246 [19] , it may be supposed that they obtain a similar mechanism of action that may cause problems with resistance. So, the search for new structures possessing antiviral activity against orthopoxviruses continues.…”
“…In comparison with ST-246, NIOCH-14 has shown comparable activity against orthopoxviruses in vitro and in vivo and similar bioavailability. [12] N(1)-isonicotinoyl-N(2)-3methyl-4-chlorobenzoylhy-drazine (IMCBH) has shown a relatively high protecting effect on vaccinia virus-infected cells in vitro, but it was inactive in experiments with infected mice or rabbits. [13] Since 2016, together with researchers from SRC VB Vector, we have been searching for novel orthopoxvirus inhibitors.…”
In this work, a library of (+)‐camphor and (−)‐fenchone based N‐acylhydrazones, amides, and esters, including para‐substituted aromatic/hetaromatic/cyclohexane ring was synthesized, with potent orthopoxvirus inhibitors identified among them. Investigations of the structure‐activity relationship revealed the significance of the substituent at the para‐position of the aromatic ring. Also, the nature of the linker between a hydrophobic moiety and aromatic ring was clarified. Derivatives with p‐Cl, p‐Br, p‐CF3, and p‐NO2 substituted aromatic ring and derivatives with cyclohexane ring showed the highest antiviral activity against vaccinia virus, cowpox, and ectromelia virus. The hydrazone and the amide group were more favourable as a linker for antiviral activity than the ester group. Compounds 3 b and 7 e with high antiviral activity were examined using the time‐of‐addition assay and molecular docking study. The results revealed the tested compounds to inhibit the late processes of the orthopoxvirus replication cycle and the p37 viral protein to be a possible biological target.
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