Virucidal nano-perforator of viral membrane trapping viral RNAs in the endosome

Kong, Byoungjae; Moon, Seokoh; Kim, Yuna; Heo, Pilwon; Jung, Younghun; Yu, Seok Hyeon; Chung, Woo‐Jae; Ban, Choongjin; Kim, Yong Ho; Kim, Paul; Hwang, Beom Jeung; Shin, Young Kil; Seong, Baik Lin; Kweon, Dae Hyuk

doi:10.1038/s41467-018-08138-1

Cited by 41 publications

(30 citation statements)

References 43 publications

(52 reference statements)

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“…The peptide bound specifically to HIV-1 by interacting with gp41 and was shown to prevent viral replication in a dose-dependent manner. In addition, phospholipids can be rearranged into a planar nanostructure known as nanodiscs [ 280 ]. When conjugated with sialic acid, nanodiscs have been able to selectively bind to H1N1, H3N2, and H5N2 viruses and neutralize their infectivity in a plaque assay.…”

Section: Nanotechnology Interventionsmentioning

confidence: 99%

Nanotechnology for virus treatment

et al. 2021

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Section: Nanotechnology Interventionsmentioning

confidence: 99%

Nanotechnology for virus treatment

et al. 2021

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“…After 4, 6, and 8 h, the cells were washed thrice with PBS for 5 min and fixed in 100% methanol. Influenza A virus particles were detected though immunofluorescence of NA as previously reported ( 17 ). Anti-influenza A virus NP antibody and Alexa Fluor 647-labeled goat-anti mouse IgG H&L antibody (Abcam, Cambridge, MA, USA) were used.…”

Section: Methodsmentioning

confidence: 80%

Morin Hydrate Inhibits Influenza Virus entry into Host Cells and Has Anti-inflammatory Effect in Influenza-infected Mice

et al. 2020

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Influenza virus is the major cause of seasonal and pandemic flu. Currently, oseltamivir, a potent and selective inhibitor of neuraminidase of influenza A and B viruses, is the drug of choice for treating patients with influenza virus infection. However, recent emergence of oseltamivir-resistant influenza viruses has limited its efficacy. Morin hydrate (3,5,7,2′,4′-pentahydroxyflavone) is a flavonoid isolated from Morus alba L. It has antioxidant, anti-inflammatory, neuroprotective, and anticancer effects partly by the inhibition of the NF-кB signaling pathway. However, its effects on influenza virus have not been studied. We evaluated the antiviral activity of morin hydrate against influenza A/Puerto Rico/8/1934 (A/ PR/8; H1N1) and oseltamivir-resistant A/PR/8 influenza viruses in vitro. To determine its mode of action, we carried out time course experiments, and time of addition, hemolysis inhibition, and hemagglutination assays. The effects of the co-administration of morin hydrate and oseltamivir were assessed using the murine model of A/PR/8 infection. We found that morin hydrate reduced hemagglutination by A/PR/8 in vitro. It alleviated the symptoms of A/PR/8infection, and reduced the levels of pro-inflammatory cytokines and chemokines, such as TNF-α and CCL2, in infected mice. Co-administration of morin hydrate and oseltamivir phosphate reduced the virus titers and attenuated pulmonary inflammation. Our results suggest that morin hydrate exhibits antiviral activity by inhibiting the entry of the virus.

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“…The virucidal effect was the strongest activity observed for RcP which might suggest that an anti-CHIKV mechanism of action for this complex might be related to a direct action on the viral particle envelope. Previous studies have shown that the virucidal effect of several compounds is closely related to an action on the virus envelope (Tang et al, 1990;Schuhmacher et al, 2003;Carravilla et al, 2017;Kong et al, 2019;Russo et al, 2019). This suggests the existence of interactions between CHIKV envelope glycoproteins and RcP.…”

Section: Discussionmentioning

confidence: 93%

Organometallic Complex Strongly Impairs Chikungunya Virus Entry to the Host Cells

et al. 2020

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Chikungunya fever is a disease caused by the Chikungunya virus (CHIKV) that is transmitted by the bite of the female of Aedes sp. mosquito. The symptoms include fever, muscle aches, skin rash, and severe joint pains. The disease may develop into a chronic condition and joint pain for months or years. Currently, there is no effective antiviral treatment against CHIKV infection. Treatments based on natural compounds have been widely studied, as many drugs were produced by using natural molecules and their derivatives. Alpha-phellandrene (α-Phe) is a naturally occurring organic compound that is a ligand for ruthenium, forming the organometallic complex [Ru2Cl4(p-cymene)2] (RcP). Organometallic complexes have shown promising as candidate molecules to a new generation of compounds that presented relevant biological properties, however, there is a lack of knowledge concerning the anti-CHIKV activity of these complexes. The present work evaluated the effects of the RcP and its precursors, the hydrate ruthenium(III) chloride salt (RuCl3⋅xH2O) (Ru) and α-Phe, on CHIKV infection in vitro. To this, BHK-21 cells were infected with CHIKV-nanoluciferase (CHIKV-nanoluc), a viral construct harboring the nanoluciferase reporter gene, at the presence or absence of the compounds for 16 h. Cytotoxicity and impact on infectivity were analyzed. The results demonstrated that RcP exhibited a strong therapeutic potential judged by the selective index > 40. Antiviral effects of RcP on different stages of the CHIKV replicative cycle were investigated; the results showed that it affected early stages of virus infection reducing virus replication by 77% at non-cytotoxic concentrations. Further assays demonstrated the virucidal activity of the compound that completely blocked virus infectivity. In silico molecular docking calculations suggested different binding interactions between aromatic rings of RcP and the loop of amino acids of the E2 envelope CHIKV glycoprotein mainly through hydrophobic interactions. Additionally, infrared spectroscopy spectral analysis indicated interactions of RcP with CHIKV glycoproteins. These data suggest that RcP may act on CHIKV particles, disrupting virus entry to the host cells. Therefore, RcP may represent a strong candidate for the development of anti-CHIKV drugs.

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Virucidal nano-perforator of viral membrane trapping viral RNAs in the endosome

Cited by 41 publications

References 43 publications

Nanotechnology for virus treatment

Nanotechnology for virus treatment

Morin Hydrate Inhibits Influenza Virus entry into Host Cells and Has Anti-inflammatory Effect in Influenza-infected Mice

Organometallic Complex Strongly Impairs Chikungunya Virus Entry to the Host Cells

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