Biology subjects

Espano, E.

Publications and source records attributed to Espano, E..

2 recordsLinked to original sources

bioRxiv2024

Teicoplanin attenuates RNA virus infection in vitro

Teicoplanin (TP) is a glycopeptide antibiotic used for Gram-positive bacterial infections, and it has been reported to inhibit SARS-CoV-2 and Ebola virus entry through cathepsin inhibition. Given that TP can inhibit viruses belonging to different virus families, we aimed to expand the potential targets of TP to determine whether TP can be developed as a broad-spectrum antiviral agent. Considering the original indication of TP, we first determined the effects of TP against viruses that cause respiratory tract infections and found that TP inhibits enveloped and non-enveloped RNA viruses, namely: human and avian influenza viruses; representative coronaviruses including porcine epidemic diarrhea virus (PEDV), human coronavirus OC43 (HCoV-OC43), and SARS-CoV-2; measles virus; human respiratory syncytial virus A2; and enterovirus 71 (EV-71). Representative flaviviruses, Zika virus (ZIKV) and dengue virus serotype 2 (DENV2), were also susceptible to inhibition by TP. In contrast, TP did not attenuate infection of human adenovirus 5, a non-enveloped DNA virus. Addition of TP at the endocytosis stage but not at the attachment/binding stage of PEDV infection reduced PEDV production in vitro, indicating cathepsin inhibition. Meanwhile, addition of TP during either the attachment/binding or the endocytosis stage of ZIKV infection reduced ZIKV particle production in host cells, and in silico modeling suggested that TP has potential binding pockets in the envelope proteins of ZIKV and DENV2. These results show that TP can be developed as a broad-spectrum antiviral especially against RNA viruses, with potentially different targets in the replication cycle of various viruses.

microbiology↗

bioRxiv2022

Chelerythrine as an anti-Zika virus agent: therapeutic potential and mode of action

Zika virus (ZIKV) is a mosquito-borne virus that has been associated with adult and neonatal neurological conditions. So far, there is no approved drug or vaccine against ZIKV infection; thus, ZIKV remains a global health threat. Here, we explored the effects of chelerythrine (CTC), a known protein kinase C (PKC) inhibitor, against ZIKV infection in cell culture models to determine its potential as a therapeutic agent for ZIKV infection. We found that CTC protected Vero cells from ZIKV-induced cytopathic effects in a dose-dependent manner. It also reduced the production of ZIKV in Vero and A549 cells. In contrast, other PKC inhibitors failed to protect Vero cells from ZIKV-induced cytopathic effects, indicating PKC-independent mechanisms underlying the effects of CTC on ZIKV. Further investigation suggested that CTC inhibited ZIKV attachment/binding rather than internalization in the host cells. Pretreatment of cell-free ZIKV particles rather than pretreatment of cells with CTC resulted in reduced ZIKV infectivity in vitro, indicating that CTC blocked the attachment/binding of the ZIKV particles to host factors. In silico analyses suggested that these effects are potentially due to the binding of CTC to the ZIKV E protein, which may occlude the interaction of the E protein with attachment factors or receptors on the host cell surface. Overall, our findings suggest that CTC reduces the infectivity of ZIKV particles through PKC- and cell-independent mechanisms. Our findings also support further exploration of CTC as an anti-ZIKV agent.

microbiology↗