Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jul-Aug;11(4):353-366.
doi: 10.22038/AJP.2020.17215.

Inhibitory activity of limonoids from Khaya grandifoliola C.DC (Meliaceae) against hepatitis C virus infection in vitro

Affiliations

Inhibitory activity of limonoids from Khaya grandifoliola C.DC (Meliaceae) against hepatitis C virus infection in vitro

Arnaud Fondjo Kouam et al. Avicenna J Phytomed. 2021 Jul-Aug.

Abstract

Objective: A fraction from Khaya grandifoliola has recently been shown to inhibit hepatitis C virus (HCV) infection and three limonoids (17-epi-methyl-6-hydroxylangolensate, 7-deacetoxy-7-oxogedunin and 7-deacetoxy-7R-hydroxygedunin) were purified from this fraction. The present study aimed at assessing the inhibitory effect of these limonoids on HCV using cell-culture derived HCV (HCVcc) system.

Materials and methods: Cytotoxic effects of the limonoids on Huh7.5 cells were assessed by MTT assay. Huh7.5 cells were transfected with RNA transcripts of the plasmid Jc1/GLuc2a, carrying a Gaussia luciferase reporter gene to rescue the HCVcc particles which were used to infect naïve cells in the presence or absence of the studied limonoids during 72 hr. Infection and replication rates were monitored by luciferase reporter assay and immunofluorescence assay (IFA) while cellular gene expression was analyzed by western blot, respectively.

Results: The limonoids inhibited HCV infection mostly by targeting entry and replication stage. Their inhibitory effect on entry step, comparable to that of anti-CD81 antibody, was related to the blocking of CD81 receptor. In the replication step, the limonoids decreased the expression of NS5B similar to danoprevir. These compounds also significantly decreased but up-regulated the expression of Class-III phosphatidylinositol 4-kinase alpha and 2',5'-oligoadenylate synthase-3, respectively.

Conclusion: The present findings suggest that limonoids from K. grandifoliola are potential anti-HCV agents and may offer an advantage in the treatment of HCV infection.

Keywords: 2’; 5’- oligoadenylate synthase-3; Anti-HCV infection; Class III phosphatidylinositol 4-kinase alpha; Khaya grandifoliola; Limonoids.

PubMed Disclaimer

Conflict of interest statement

The authors have declared that there is no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structures of studied limonoids
Figure 2
Figure 2
Transfection and infection of Huh7.5
Figure 3
Figure 3
Cytotoxicity and assessment of limonoids from K. grandifoliola against Jc1/GLuc2A infectivity in Huh7.5 cells
Figure 4
Figure 4
Immunofluorescence of HCV core protein detection showing inhibitory effect of limonoids from K. grandifoliolaonHCV entry step
Figure 5
Figure 5
Antiviral mechanisms of tested limonoids in the replication step
Figure 6
Figure 6
Effect of limonoids on the expression of DGAT-1

References

    1. Averhoff FM, Glass N, Holtzman D. Global Burden of Hepatitis C: Considerations for Healthcare Providers in the United States. Clin. Infect. Dis. 2012:S10–S15. - PubMed
    1. Bartenschlager R, Cosset FL, Lohmann V, 2010 J Hepatol. Hepatitis C virus replication cycle;53:583–585. - PubMed
    1. Bartenschlager R, Sparacio S. Hepatitis C virus molecular clones and their replication capacity in vivo and in cell culture. Virus Res. 2007;127:195–207. - PubMed
    1. Belouzard S, Cocquerel L, Dubuisson J. Hepatitis C virus entry into the hepatocyte. Open Life Sci. 2011:6. - PMC - PubMed
    1. Bianco A, Reghellin V, Donnici L, Fenu S, Alvarez R, Baruffa C, Peri F, Pagani M, Abrignani S, Neddermann P, De Francesco R. Metabolism of Phosphatidylinositol 4-Kinase IIIα-Dependent PI4P Is Subverted by HCV and Is Targeted by a 4-Anilino Quinazoline with Antiviral Activity. PLoS Pathog. 2012;8:e1002576. - PMC - PubMed

LinkOut - more resources