• Biomolecules & Therapeutics
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• v.32 no.4
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• pp.481-491
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• 2024

Paxlovid is the first approved oral treatment for coronavirus disease 2019 and includes nirmatrelvir, a protease inhibitor targeting the main protease (M^pro) of SARS-CoV-2, as one of the key components. While some specific mutations emerged in M^pro were revealed to significantly reduce viral susceptibility to nirmatrelvir in vitro, there is no report regarding resistance to nirmatrelvir in patients and animal models for SARS-CoV-2 infection yet. We recently developed xenograft tumors derived from Calu-3 cells in immunodeficient mice and demonstrated extended replication of SARS-CoV-2 in the tumors. In this study, we investigated the effect of nirmatrelvir administration on SARS-CoV-2 replication. Treatment with nirmatrelvir after virus infection significantly reduced the replication of the parental SARS-CoV-2 and SARS-CoV-2 Omicron at 5 days post-infection (dpi). However, the virus titers were completely recovered at the time points of 15 and 30 dpi. The virus genomes in the tumors at 30 dpi were analyzed to investigate whether nirmatrelvir-resistant mutant viruses had emerged during the extended replication of SARS-CoV-2. Various mutations in several genes including ORF1ab, ORF3a, ORF7a, ORF7b, ORF8, and N occurred in the SARS-CoV-2 genome; however, no mutations were induced in the M^pro sequence by a single round of nirmatrelvir treatment, and none were observed even after two rounds of treatment. The parental SARS-CoV-2 and its sublineage isolates showed similar IC₅₀ values of nirmatrelvir in Vero E6 cells. Therefore, it is probable that inducing viral resistance to nirmatrelvir in vivo is challenging differently from in vitro passage.

• Nonlinear Functional Analysis and Applications
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• v.28 no.2
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• pp.473-495
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• 2023

The use of mathematical modelling in the study of epidemiological disorders continues to grow substantially. In order to better support global policy initiatives and explain the possible consequence of an outbreak, mathematical models were constructed to forecast how epidemic illnesses spread. In this paper, fractional derivatives and (${\varpi}$ - F_𝓒)-contractions are used to explore the existence and uniqueness solutions of the novel coronavirus-19 model.

• Journal of the Korean Crystal Growth and Crystal Technology
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• v.29 no.6
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• pp.270-275
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• 2019

Mica capacitor is being adopted for high voltage firing unit of guided weapon system because of its superior impact enduring property relative to ceramic capacitor. Reliability of localized mica high voltage capacitors was verified through environmental test like terminal strength test, humidity test, thermal shock test and accelerated life test for application to high voltage firing unit. Failure mode of mica capacitor is a decrease of insulation resistance and its final dielectric breakdown. Main constants of accelerated life model were derived experimentally and voltage constant and activation energy were 5.28 and 0.805 eV respectively. Lifetime of mica capacitor at normal use condition was calculated to be 38.5 years by acceleration factor, 496, and lifetime at accelerated condition and this long lifetime confirmed that mica high voltage capacitor could be applied for firing unit.