DNA virus infections are often lifelong and can cause serious diseases in their hosts. Their recognition by the sensors of the innate immune system represents the front line of host defence. Understanding the molecular mechanisms of innate immunity responses is an important prerequisite for the design of effective antivirotics. This review focuses on the present state of knowledge surrounding the mechanisms of viral DNA genome sensing and the main induced pathways of innate immunity responses. The studies that have been performed to date indicate that herpesviruses, adenoviruses, and polyomaviruses are sensed by various DNA sensors. In non-immune cells, STING pathways have been shown to be activated by cGAS, IFI16, DDX41, or DNA-PK. The activation of TLR9 has mainly been described in pDCs and in other immune cells. Importantly, studies on herpesviruses have unveiled novel participants (BRCA1, H2B, or DNA-PK) in the IFI16 sensing pathway. Polyomavirus studies have revealed that, in addition to viral DNA, micronuclei are released into the cytosol due to genotoxic stress. Papillomaviruses, HBV, and HIV have been shown to evade DNA sensing by sophisticated intracellular trafficking, unique cell tropism, and viral or cellular protein actions that prevent or block DNA sensing. Further research is required to fully understand the interplay between viruses and DNA sensors.

• MeSH
• DNA virů metabolismus   MeSH
• Herpesviridae * genetika   metabolismus   MeSH
• infekce DNA virem * MeSH
• lidé MeSH
• Polyomavirus * genetika   MeSH
• přirozená imunita MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Viral proteases are indispensable for successful virion maturation, thus making them a prominent drug target. Their enzyme activity is tightly spatiotemporally regulated by expression in the precursor form with little or no activity, followed by activation via autoprocessing. These cleavage events are frequently triggered upon transportation to a specific compartment inside the host cell. Typically, precursor oligomerization or the presence of a co-factor is needed for activation. A detailed understanding of these mechanisms will allow ligands with non-canonical mechanisms of action to be designed, which would specifically modulate the initial irreversible steps of viral protease autoactivation. Binding sites exclusive to the precursor, including binding sites beyond the protease domain, can be exploited. Both inhibition and up-regulation of the proteolytic activity of viral proteases can be detrimental for the virus. All these possibilities are discussed using examples of medically relevant viruses including herpesviruses, adenoviruses, retroviruses, picornaviruses, caliciviruses, togaviruses, flaviviruses, and coronaviruses.

• MeSH
• antivirové látky farmakologie   MeSH
• Flavivirus účinky léků   metabolismus   MeSH
• Herpesviridae účinky léků   metabolismus   MeSH
• HIV-1 účinky léků   MeSH
• inhibitory virových proteáz farmakologie   MeSH
• lidé MeSH
• lidské adenoviry účinky léků   metabolismus   MeSH
• SARS-CoV-2 účinky léků   metabolismus   MeSH
• virové nemoci farmakoterapie   MeSH
• virové proteasy biosyntéza   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

This review article is the first in the series providing an overview of currently used antiviral drugs and presenting contemporary approaches to their analysis. Large number of available antivirals and their structural variability makes this task very challenging. Trying to cover this topic comprehensively while maintaining reasonable size of the article, the review is presented in two parts. For the purpose of the overall review, antivirals were divided into four groups: (i) antivirals against herpes viruses, (ii) antivirals against respiratory viruses, (iii) antivirals against hepatitis viruses, and (iv) antivirals against HIV. Part one is devoted to the groups (i) and (ii) and also concerns the key features of the bioanalytical method. The mechanisms of action of antivirals against respiratory and herpes viruses and their use in clinical practice are briefly outlined, and the analytical methods for selected representatives of each class are described in more detail. The methods developed for the determination of drugs from these classes mostly include conventional procedures. In contrast, current trends such as UHPLC are used rarely and proper method validation based on requirements of bioanalytical guidelines can be often considered insufficient.

• MeSH
• antivirové látky analýza   terapeutické užití   MeSH
• biologické faktory analýza   MeSH
• Herpesviridae účinky léků   metabolismus   MeSH
• herpetické infekce farmakoterapie   metabolismus   MeSH
• infekce dýchací soustavy farmakoterapie   metabolismus   MeSH
• lidé MeSH
• tandemová hmotnostní spektrometrie metody   MeSH
• virové nemoci farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Lamins are the best characterized cytoskeletal components of the cell nucleus that help to maintain the nuclear shape and participate in diverse nuclear processes including replication or transcription. Nuclear actin is now widely accepted to be another cytoskeletal protein present in the nucleus that fulfills important functions in the gene expression. Some viruses replicating in the nucleus evolved the ability to interact with and probably utilize nuclear actin for their replication, e.g., for the assembly and transport of capsids or mRNA export. On the other hand, lamins play a role in the propagation of other viruses since nuclear lamina may represent a barrier for virions entering or escaping the nucleus. This review will summarize the current knowledge about the roles of nuclear actin and lamins in viral infections.

• MeSH
• aktiny metabolismus   MeSH
• Baculoviridae metabolismus   patogenita   MeSH
• buněčné jádro metabolismus   virologie   MeSH
• cytoskelet MeSH
• Herpesviridae metabolismus   patogenita   MeSH
• herpetické infekce metabolismus   patologie   virologie   MeSH
• laminy metabolismus   MeSH
• lidé MeSH
• replikace viru MeSH
• Retroviridae metabolismus   patogenita   MeSH
• retrovirové infekce metabolismus   patologie   virologie   MeSH
• sestavení viru MeSH
• virové nemoci metabolismus   virologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH