Biology subjects

Meiyanto, E.

Publications and source records attributed to Meiyanto, E..

2 recordsLinked to original sources

bioRxiv2024

The effect of Citrus reticulata peel extract containing hesperidin on inhibition of SARS-CoV-2 infection based on pseudovirus entry assays

Orange (Citrus reticulata Blanco) peel contains a flavonoid glycoside hesperidin (HSD) as the primary component. HSD, upon enzymatic hydrolysis, forms hesperetin (HST) aglycone derivate. These two flavonoids have been predicted to have in-silico affinities for ACE2 and SARS-CoV-2 spike, crucial proteins in SARS-CoV-2 infection mechanisms. However, in vitro antiviral testing of orange peel extract, HSD, and HST has not been reported. This study presents for the first time a pseudovirus entry assay approach to test the anti-SARS-CoV-2 effect of HSD, HST, and orange peel extract prepared by hydrodynamic cavitation (HCV). We used a non-virulent pseudovirus model as an alternative to the original virus to target the entry point and enable research to be conducted outside the BSL-3 facility. Based on HPLC analysis, the test results showed that HCV contained HSD at about 4% w/w. Moreover, HSD 1 and 10 M, HST 10 M, and HCV 1 g/ml showed inhibition of pseudovirus entry in 293/hACE2 cells with percentages inhibition 25.92, 37.40, 27.32, and 38.97 %, respectively. Despite HCV 1 g/ml showing about 6 % lower inhibitory activity than HSD 1 M in pseudovirus entry assay, it holds potential as a supplement or source of raw material for HSD as a SARS-CoV-2 antiviral.

pharmacology and toxicology↗

bioRxiv2023

The placental protein NRK promotes cell death through its plasma membrane-localizing CNH domain

Placental development is regulated by the balance between cell proliferation and death. The placental protein NRK (NIK-related kinase) plays a role in preventing excessive placenta growth. We previously demonstrated that NRK underwent rapid molecular evolution in the ancestor of placental mammals and acquired the functional regions, including the phospholipid-binding citron homology (CNH) domain, by which NRK inhibits cell proliferation. NRK is also potentially responsible for cell death; caspases cleave NRK during apoptosis, releasing the C-terminal fragment that promotes cell death. Here, we explored the molecular mechanisms underlying the cell death-promoting effects of NRK. Our experimental data using HeLa, placenta trophoblast BeWo (human), and Rcho-1 (rat) cells indicated that the CNH domain of NRK was required and sufficient to promote cell death. In vitro and in silico studies showed the NRK CNH domain bound to phospholipids via its polybasic clusters and remains at the plasma membrane (PM) during apoptosis. Evolutional analyses indicated that these clusters formed in the ancestor of placental mammals. Mutations in these clusters (CNH-18A) hindered the cell death-promoting activity of the CNH domain. We concluded that NRK promotes cell death through its plasma membrane-localizing CNH domain and suggested its active role in PM-associated events during cell death.

cell biology↗