Host-pathogen interactions are complex associations which evolve over long co-evolutionary histories. Pathogens exhibit different mechanisms to gain advantage over their host. Mimicry of host factors is an influential tool in subverting host mechanisms to ensure pathogenesis. This chapter discusses such molecular mimicry exhibited during viral infections. Understanding the evolutionary relationships, shared identity and functional impact of the virus encoded mimics is critical. With a particular emphasis on viral mimics and their association with cancer and autoimmune diseases, this chapter highlights the importance of molecular mimicry in virus biology.
- Klíčová slova
- Autoimmune diseases, Cancer, Host-pathogen interaction, Infectious diseases, Virus,
- MeSH
- autoimunitní nemoci metabolismus virologie imunologie MeSH
- endokrinní systém metabolismus MeSH
- interakce hostitele a patogenu MeSH
- lidé MeSH
- molekulární mimikry * MeSH
- nádory metabolismus virologie MeSH
- virové nemoci metabolismus virologie imunologie MeSH
- viry metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Diphyllin is a natural arylnaphtalide lignan extracted from tropical plants of particular importance in traditional Chinese medicine. This compound has been described as a potent inhibitor of vacuolar (H+)ATPases and hence of the endosomal acidification process that is required by numerous enveloped viruses to trigger their respective viral infection cascades after entering host cells by receptor-mediated endocytosis. Accordingly, we report here a revised, updated, and improved synthesis of diphyllin, and demonstrate its antiviral activities against a panel of enveloped viruses from Flaviviridae, Phenuiviridae, Rhabdoviridae, and Herpesviridae families. Diphyllin is not cytotoxic for Vero and BHK-21 cells up to 100 µM and exerts a sub-micromolar or low-micromolar antiviral activity against tick-borne encephalitis virus, West Nile virus, Zika virus, Rift Valley fever virus, rabies virus, and herpes-simplex virus type 1. Our study shows that diphyllin is a broad-spectrum host cell-targeting antiviral agent that blocks the replication of multiple phylogenetically unrelated enveloped RNA and DNA viruses. In support of this, we also demonstrate that diphyllin is more than just a vacuolar (H+)ATPase inhibitor but may employ other antiviral mechanisms of action to inhibit the replication cycles of those viruses that do not enter host cells by endocytosis followed by low pH-dependent membrane fusion.
- Klíčová slova
- antiviral activity, cleistanthin B, cytotoxicity, diphyllin, enveloped virus, vacuolar ATPase inhibitor,
- MeSH
- antigeny virové metabolismus MeSH
- antivirové látky chemická syntéza farmakologie MeSH
- buněčné linie MeSH
- glukosidy farmakologie MeSH
- lignany chemická syntéza farmakologie MeSH
- replikace viru účinky léků MeSH
- vakuolární protonové ATPasy antagonisté a inhibitory MeSH
- viabilita buněk účinky léků MeSH
- viry klasifikace účinky léků metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antigeny virové MeSH
- antivirové látky MeSH
- cleistanthin B MeSH Prohlížeč
- diphyllin MeSH Prohlížeč
- glukosidy MeSH
- lignany MeSH
- vakuolární protonové ATPasy MeSH
G-quadruplexes contribute to the regulation of key molecular processes. Their utilization for antiviral therapy is an emerging field of contemporary research. Here we present comprehensive analyses of the presence and localization of putative G-quadruplex forming sequences (PQS) in all viral genomes currently available in the NCBI database (including subviral agents). The G4Hunter algorithm was applied to a pool of 11,000 accessible viral genomes representing 350 Mbp in total. PQS frequencies differ across evolutionary groups of viruses, and are enriched in repeats, replication origins, 5'UTRs and 3'UTRs. Importantly, PQS presence and localization is connected to viral lifecycles and corresponds to the type of viral infection rather than to nucleic acid type; while viruses routinely causing persistent infections in Metazoa hosts are enriched for PQS, viruses causing acute infections are significantly depleted for PQS. The unique localization of PQS identifies the importance of G-quadruplex-based regulation of viral replication and life cycle, providing a tool for potential therapeutic targeting.
- Klíčová slova
- Acute infection, Bioinformatics, G-quadruplex, G4Hunter, Persistent infection, Viral genome,
- MeSH
- databáze nukleových kyselin * MeSH
- DNA virů genetika metabolismus MeSH
- G-kvadruplexy * MeSH
- genom virový * MeSH
- lidé MeSH
- virové nemoci * genetika metabolismus MeSH
- viry * genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- DNA virů MeSH
The term 'receptor' is generally accepted as the cell-surface component that participates in virus binding and facilitates subsequent viral infection. Recent advances in technology have permitted the identification of several virus receptors, increasing our understanding of the significance of this initial virus-cell and virus-host interaction. Virus binding was previously considered to involve simple recognition and attachment to a single cell surface molecule by virus attachment proteins. The classical concept of these as single entities that participate in a lock-and-key-type process has been superseded by new data indicating that binding can be a multistep process, often involving different virus-attachment proteins and more than one host-cell receptor.
- MeSH
- virové nemoci veterinární virologie MeSH
- virové receptory metabolismus MeSH
- viry metabolismus patogenita MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- virové receptory MeSH
This article reviews diverse strategies of rational development of antivirals based upon an interference with processes involved in viral multiplication cycle. With the aid of approved antiviral drugs as well as of antiviral drugs candidates in diverse stages of development this review demonstrates broad variability of chemical structure and mechanism of action in the field of antiviral development.
- MeSH
- antivirové látky chemie farmakologie MeSH
- viry účinky léků metabolismus MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- antivirové látky MeSH
- MeSH
- Bacteria enzymologie růst a vývoj metabolismus MeSH
- bibliografie jako téma * MeSH
- Eukaryota enzymologie růst a vývoj metabolismus MeSH
- houby enzymologie růst a vývoj metabolismus MeSH
- kultivace virů MeSH
- kultivační média MeSH
- mikrobiální genetika MeSH
- teoretické modely MeSH
- viry enzymologie růst a vývoj metabolismus MeSH
- zdravotnické prostředky MeSH
- Publikační typ
- bibliografie MeSH
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- kultivační média MeSH