Biology subjects

Paramitasari, K. A.

Publications and source records attributed to Paramitasari, K. A..

3 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

Curcumin and turmeric extract inhibited SARS-CoV-2 pseudovirus cell entry and Spike mediated cell fusion

Turmeric extract (TE) with curcumin as its main active ingredient has been studied as a potential COVID-19 therapeutic. Curcumin has been studied in silico and in vitro against a naive SARS-CoV-2 virus, yet little is known about TEs impact on SARS-CoV-2 infection. Moreover, no study reveals the potential of both curcumin and TE on the inhibition of SARS-CoV-2 cell-to-cell transmission. Here, we investigated the effects of both curcumin and TE on inhibiting SARS-CoV-2 entry and cell-to-cell transmission using pseudovirus (PSV) and syncytia models. We performed a PSV entry assay in 293T or 293 cells expressing hACE2. The cells were pretreated with curcumin or TE and then treated with PSV with or without the test samples. Next, we carried out syncytia assay by co-transfecting 293T cells with plasmids encoding spike, hACE2, and TMPRSS2 to be treated with the test samples. The results showed that in PSV entry assay on 293T/hACE/TMPRSS2 cells, both curcumin and TE inhibited PSV entry at concentrations of 1 {micro}M and 10 {micro}M for curcumin and 1 {micro}g/ml and 10 {micro}g/ml for TE. Moreover, both curcumin and TE reduced syncytia formation compared to control cells. Our study shows that TE and curcumin are potential inhibitors of SARS-CoV-2 infection at entry points, either by direct or indirect infection models. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=164 SRC="FIGDIR/small/560070v2_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@18f3faforg.highwire.dtl.DTLVardef@19e2818org.highwire.dtl.DTLVardef@5a6670org.highwire.dtl.DTLVardef@fb82d8_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2023

Sensitization with an allogeneic MHC class I molecule induces anti-tumor immunity in the absence of PD-1 in mice

To investigate the effect of a major histocompatibility complex class I (MHC-I) overexpression to augment immune sensitivity against tumors, we have generated the murine colorectal carcinoma cell line MC38 (with the endogenous H-2b haplotype) overexpressing the allogeneic mouse MHC-I cell surface molecule H-2Kd (MC38 H-2Kd). The tumorigenicity of unmodified parental cells (MC38 PT) and MC38 H-2Kd was tested in vivo by subcutaneous injection into the flank of wild-type (WT) and programmed death-1 (PD-1) knockout (KO) mice in a C57BL/6 (H-2b) genetic background. MC38 PT cells readily formed tumors and grew progressively in both WT and PD-1 KO mice. The speed of MC38 PT tumor growth was slower in PD-1 KO mice than in WT mice. In contrast, MC38 H-2Kd cells showed full sensitivity to rejection by the immune system in both naive WT and PD-1 KO mice, indicated by spontaneous tumor regression. Next, we sought to determine the extent to which H-2Kd-overexpressing tumors could protect the mice against unmodified cancers. PD-1 KO mice were first sensitized with highly immunogenic MC38 H-2Kd cells and then challenged with weakly immunogenic MC38 PT cells. Intriguingly, all PD-1 KO mice gained immunity against the aggressive MC38 tumor and became tumor-free. Sensitizing PD-1 KO mice with growth-arrested (by the pre-treatment with mitomycin C, MMC) and the debris of MC38 H-2Kd tumors also provided full protection against the growth of secondary MC38 PT tumors. Most notably, sensitization with the debris of MC38 H-2Kd cells provided the long-term immunological memory against MC38 PT carcinoma cells. This finding implies that MC38 H-2Kd cells retain highly efficient and durable immunogenicity.

immunology↗