Zinc Influx Restricts Enterovirus D68 Replication

Abstract

Enterovirus D68 (EV-D68) is a respiratory viral pathogen that causes severe respiratory diseases and neurologic manifestations. Since the 2014 outbreak, EV-D68 has been reported to cause severe complications worldwide. However, there are currently no approved antiviral agents or vaccines for EV-D68. In this study, we found that zinc ions exerted substantial antiviral activity against EV-D68 infection in vitro. Zinc salt treatment potently suppressed EV-D68 RNA replication, protein synthesis, and infectious virion production and inhibited cytopathic effects without producing significant cytotoxicity at virucidal concentrations (EC50=0.033mM). Zinc chloride (ZnCl2) treatment moderately inhibited EV-D68 attachment. Time-dose analysis of EV-D68 structural protein VP1 synthesis showed stronger suppression of VP1 in the culture medium than that in the cell lysates. Furthermore, a zinc ionophore, pyrrolidine dithiocarbamate, which can transport zinc ions into cells, also enhanced the anti-EV-D68 activity of ZnCl2 treatment. Taken together, our results demonstrated that the enhancement of zinc influx could serve as a powerful strategy for the therapeutic treatment of EV-D68 infections.

Antiviral activity of zinc against hepatitis viruses: current status and future prospects

“…It also enhances T cell and antibody mediated immunity in mice, have adjuvant like properties and thus reduces chances of reinfection ( Antoine et al, 2016 ; Samad et al, 2021 ). Zinc treatment was shown to moderately inhibit enterovirus D68 attachment and entry into target cells ( Figure 3 ; Liu et al, 2021 ). In the case of Rhinovirus, zinc may act as a competitive inhibitor of virus binding to the ICAM1 (intercellular adhesion molecule 1) on the host cell surface, which is the receptor for virus entry ( Hulisz, 2004 ; Figure 3 ).…”

“…Antiviral effect of zinc have been demonstrated in vivo and in vitro in several viruses, including corona viruses, picornaviruses, papilloma viruses, metapneumoviruses, rhinoviruses, herpes simplex viruses, varicella-zoster viruses, respiratory syncytial viruses, retroviruses, SARS-CoV and SARS-CoV-2 etc. ( Bracha and Schlesinger, 1976 ; Gupta and Rapp, 1976 ; Polatnick and Bachrach, 1978 ; Katz and Margalith, 1981 ; Kümel et al, 1990 ; Hulisz, 2004 ; Krenn et al, 2009 ; Te Velthuis et al, 2010 ; Liu and Kielian, 2012 ; Wei et al, 2012 ; Antoine et al, 2016 ; Liu et al, 2021 ; Samad et al, 2021 ). Based on the available literature, mechanism underlying the antiviral properties of zinc may be broadly classified into two categories: (a) direct inhibitory effect on the different stages of the life cycle of the virus and (b) indirect effect of zinc attributed to its ability to modulate various host cellular processes and immune response.…”

Synthesis and Antimicrobial Applications of ZnO Nanostructures: A Review

“…It is noteworthy that most of the papers available in literature deal with the use of Zn 2+ ions as antiviral agents, rather than ZnO NSs, possibly in combination with other molecules like lactoferrin, heparin, etc. − Zinc ions can penetrate cell walls (especially when driven by ionophores), augmenting the intracellular Zn 2+ concentration and subsequently impairing virus replication . Bhatti and DeLong recently reviewed the antiviral application of different nanomaterials, including ZnO NSs: in that paper, ROS generated through photocatalytic reactions driven by UV–Vis light on ZnO NSs are indicated as the main species responsible for damaging of the viral envelopes, interfering with viral entry and replication …”

Hubungan Pengetahuan dan Kesadaran terhadap COVID-19 dengan Asupan Vitamin D dan Seng pada Mahasiswa Kedokteran UNS

“…Hal ini menunjukkan bahwa seng dapat memainkan peran kunci dalam pertahanan host terhadap virus RNA. Replikasi in vitro virus influenza dihambat oleh zinc ionophore pyrrolidine dithiocarbamate (Liu et al, 2021). Selain itu, ada indikasi bahwa seng dapat menghambat replikasi SARS-CoV in vitro (Asl et al, 2021).…”