AT-9010 (2'-methyl-2'-fluoro guanosine triphosphate) is a GTP analog whose prodrug, AT-752 is under consideration in human medicine as a potential antiviral drug against certain flaviviruses. It was previously believed to inhibit viral replication by acting primarily as a chain terminator. However, it was discovered recently that it also binds the GTP binding site of the methyltransferase (MTase) domain of the orthoflavivirus polymerase, thus interfering with RNA capping. Here, we investigated the binding of AT-9010 to Ntaya and Zika virus MTases. Structural analysis using X-ray crystallography revealed similar interactions between the base and sugar moieties of AT-9010 and key residues in both MTases, although differences in hydrogen bonding were observed. Our analysis also suggested that the triphosphate part of AT-9010 is flexible. Despite minor variations, the overall binding mode of AT-9010 was found to be the same for all of the flaviviral MTases examined, suggesting a structural basis for the efficacy of AT-9010 against multiple orthoflavivirus MTases.

• MeSH
• adenosin analogy a deriváty   MeSH
• antivirové látky * farmakologie   metabolismus   chemie   MeSH
• Flavivirus enzymologie   MeSH
• guanosintrifosfát metabolismus   MeSH
• krystalografie rentgenová MeSH
• methyltransferasy * metabolismus   chemie   MeSH
• molekulární modely MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• virové proteiny metabolismus   chemie   genetika   MeSH
• virus zika enzymologie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adenosin MeSH
• antivirové látky * MeSH
• guanosintrifosfát MeSH
• methyltransferasy * MeSH
• sinefungin MeSH Prohlížeč
• virové proteiny MeSH

Monkeypox is a disease with pandemic potential. It is caused by the monkeypox virus (MPXV), a double-stranded DNA virus from the Poxviridae family, that replicates in the cytoplasm and must encode for its own RNA processing machinery including the capping machinery. Here, we present crystal structures of its 2'-O-RNA methyltransferase (MTase) VP39 in complex with the pan-MTase inhibitor sinefungin and a series of inhibitors that were discovered based on it. A comparison of this 2'-O-RNA MTase with enzymes from unrelated single-stranded RNA viruses (SARS-CoV-2 and Zika) reveals a conserved sinefungin binding mode, implicating that a single inhibitor could be used against unrelated viral families. Indeed, several of our inhibitors such as TO507 also inhibit the coronaviral nsp14 MTase.

• MeSH
• COVID-19 * MeSH
• infekce virem zika * MeSH
• lidé MeSH
• methyltransferasy metabolismus   MeSH
• RNA virová genetika   MeSH
• RNA MeSH
• SARS-CoV-2 genetika   MeSH
• virové nestrukturální proteiny chemie   MeSH
• virus opičích neštovic genetika   metabolismus   MeSH
• virus zika * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• methyltransferasy MeSH
• RNA virová MeSH
• RNA MeSH
• virové nestrukturální proteiny MeSH

INTRODUCTION: This study aims to describe the epidemiological characteristics of imported cases of dengue (DEN), chikungunya (CHIK), and Zika virus (ZIKV) infections in Czech travellers. MATERIALS AND METHODS: This single-centre descriptive study has retrospectively analysed data of patients with laboratory confirmed DEN, CHIK, and ZIKV infections diagnosed at the Department of Infectious, Parasitic and Tropical Diseases of the University Hospital Bulovka in Prague, Czech Republic from 2004 to 2019. RESULTS: The study included a total of 313 patients with DEN, 30 with CHIK, and 19 with ZIKV infections. Most patients travelled as tourists:263 (84.0%), 28 (93.3%), and 17 (89.5%), respectively (p = 0.337). The median duration of stay was 20 (IQR 14-27), 21 (IQR 14-29), and 15 days (IQR 14-43), respectively (p = 0.935). Peaks of imported DEN and ZIKV infections were noted in 2016, and in 2019 in the case of CHIK infection. Most cases of DEN and CHIKV infections were acquired in Southeast Asia:212 (67.7%) and 15 (50%), respectively, while ZIKV infection was most commonly imported from the Caribbean (11; 57,9%). CONCLUSIONS: Arbovirus infections represent an increasingly significant cause of illness in Czech travellers. Comprehensive knowledge of the specific epidemiological profile of these diseases is an essential prerequisite for good travel medicine practice.

• MeSH
• centra terciární péče MeSH
• dengue * epidemiologie   MeSH
• horečka chikungunya * epidemiologie   MeSH
• infekce virem zika * epidemiologie   MeSH
• lidé MeSH
• retrospektivní studie MeSH
• virus chikungunya * MeSH
• virus zika * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

The smallest of all the pathogens, viruses, have continuously been the foremost strange microorganisms. Viral infections can cause extreme sicknesses as evidenced by the HIV/AIDS widespread or the later Ebola or Zika episodes. Apprehensive framework distortions are also regularly observed as consequences of numerous viral infections. Besides, numerous viral infections are of oncoviruses, which can trigger different types of cancer. Nearly every year, a modern infectious species emerges, debilitating the world population with an annihilating episode. Subsequently, there is a need to create antivirals to combat such rising infections. From the discovery of the antiviral drug Idoxuridine in 1962 to the revelation of Baloxavir marboxil (Xofluza) that was approved by the FDA in 2018, the whole process and criteria of creating antivirals have changed significantly. In this article, different auxiliary science strategies are described that can serve as a referral for therapeutic innovation.

• Klíčová slova
• Antivirals, COVID-19, X-ray crystallography, cancer, cryo-EM, drug design, structural biology, virus,
• MeSH
• antivirové látky farmakologie   terapeutické užití   MeSH
• infekce virem zika * farmakoterapie   MeSH
• lidé MeSH
• virové nemoci * farmakoterapie   MeSH
• virus zika * MeSH
• viry * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antivirové látky MeSH

Zika virus (ZIKV) has been characterized as one of many potential pathogens and placed under future epidemic outbreaks by the WHO. However, a lack of potential therapeutics can result in an uncontrolled pandemic as with other human pandemic viruses. Therefore, prioritized effective therapeutics development has been recommended against ZIKV. In this context, the present study adopted a strategy to explore the lead compounds from Azadirachta indica against ZIKV via concurrent inhibition of the NS2B-NS3 protease (ZIKVpro) and NS5 RNA dependent RNA polymerase (ZIKVRdRp) proteins using molecular simulations. Initially, structure-based virtual screening of 44 bioflavonoids reported in Azadirachta indica against the crystal structures of targeted ZIKV proteins resulted in the identification of the top four common bioflavonoids, viz. Rutin, Nicotiflorin, Isoquercitrin, and Hyperoside. These compounds showed substantial docking energy (-7.9 to -11.01 kcal/mol) and intermolecular interactions with essential residues of ZIKVpro (B:His51, B:Asp75, and B:Ser135) and ZIKVRdRp (Asp540, Ile799, and Asp665) by comparison to the reference compounds, O7N inhibitor (ZIKVpro) and Sofosbuvir inhibitor (ZIKVRdRp). Besides, long interval molecular dynamics simulation (500 ns) on the selected docked poses reveals stability of the respective docked poses contributed by intermolecular hydrogen bonds and hydrophobic interactions. The predicted complex stability was further supported by calculated end-point binding free energy using molecular mechanics generalized born surface area (MM/GBSA) method. Consequently, the identified common bioflavonoids are recommended as promising therapeutic inhibitors of ZIKVpro and ZIKVRdRp against ZIKV for further experimental assessment.

• Klíčová slova
• Azadirachta indica, NS2B-NS3 protease, NS5 RdRp, Zika virus, flavonoids, molecular dynamics, therapeutics,
• MeSH
• antivirové látky chemie   MeSH
• Azadirachta * chemie   MeSH
• flavonoidy chemie   MeSH
• infekce virem zika * farmakoterapie   MeSH
• inhibitory proteas chemie   MeSH
• lidé MeSH
• olovo farmakologie   MeSH
• proteasy farmakologie   MeSH
• RNA-dependentní RNA-polymerasa MeSH
• simulace molekulového dockingu MeSH
• virové nestrukturální proteiny metabolismus   MeSH
• virus zika * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antivirové látky MeSH
• flavonoidy MeSH
• inhibitory proteas MeSH
• olovo MeSH
• proteasy MeSH
• RNA-dependentní RNA-polymerasa MeSH
• virové nestrukturální proteiny MeSH

The placenta provides a significant physical and physiological barrier to prevent fetal infection during pregnancy. Nevertheless, it is at times breached by pathogens and leads to vertical transmission of infection from mother to fetus. This review will focus specifically on the Zika flavivirus, the HIV retrovirus and the emerging SARS-CoV2 coronavirus, which have affected pregnant women and their offspring in recent epidemics. In particular, we will address how viral infections affect the immune response at the maternal-fetal interface and how the placental barrier is physically breached and discuss the consequences of infection on various aspects of placental function to support fetal growth and development. Improved understanding of how the placenta responds to viral infections will lay the foundation for developing therapeutics to these and emergent viruses, to minimise the harms of infection to the offspring.

• Klíčová slova
• Barrier function, Human immunodeficiency virus, Immune cells, Placenta, Pregnancy, Severe acute respiratory syndrome coronavirus 2, Syncytiotrophoblast, Viral infections, Zika virus,
• MeSH
• COVID-19 metabolismus   MeSH
• HIV infekce metabolismus   MeSH
• HIV-1 patogenita   MeSH
• infekce virem zika metabolismus   MeSH
• infekční komplikace v těhotenství epidemiologie   virologie   MeSH
• lidé MeSH
• placenta metabolismus   virologie   MeSH
• plod virologie   MeSH
• SARS-CoV-2 patogenita   MeSH
• těhotenství MeSH
• vertikální přenos infekce statistika a číselné údaje   MeSH
• virové nemoci patofyziologie   MeSH
• virus zika patogenita   MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

A series of 7-deazaadenine ribonucleosides bearing alkyl, alkenyl, alkynyl, aryl, or hetaryl groups at position 7 as well as their 5'-O-triphosphates and two types of monophosphate prodrugs (phosphoramidates and S-acylthioethanol esters) were prepared and tested for antiviral activity against selected RNA viruses (Dengue, Zika, tick-borne encephalitis, West Nile, and SARS-CoV-2). The modified triphosphates inhibited the viral RNA-dependent RNA polymerases at micromolar concentrations through the incorporation of the modified nucleotide and stopping a further extension of the RNA chain. 7-Deazaadenosine nucleosides bearing ethynyl or small hetaryl groups at position 7 showed (sub)micromolar antiviral activities but significant cytotoxicity, whereas the nucleosides bearing bulkier heterocycles were still active but less toxic. Unexpectedly, the monophosphate prodrugs were similarly or less active than the corresponding nucleosides in the in vitro antiviral assays, although the bis(S-acylthioethanol) prodrug 14h was transported to the Huh7 cells and efficiently released the nucleoside monophosphate.

• Klíčová slova
• 7-deazapurine ribonucleosides, RNA viruses, antiviral activity, monophosphate prodrugs, triphoshates,
• MeSH
• antivirové látky farmakologie   MeSH
• COVID-19 virologie   MeSH
• farmakoterapie COVID-19 MeSH
• fosfáty farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• prekurzory léčiv farmakologie   MeSH
• purinové nukleosidy MeSH
• puriny farmakologie   MeSH
• ribonukleosidy farmakologie   MeSH
• RNA-dependentní RNA-polymerasa metabolismus   MeSH
• RNA-viry účinky léků   MeSH
• SARS-CoV-2 účinky léků   MeSH
• virus dengue účinky léků   MeSH
• virus západního Nilu účinky léků   MeSH
• virus zika účinky léků   MeSH
• viry klíšťové encefalitidy účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 7-deazapurine MeSH Prohlížeč
• antivirové látky MeSH
• fosfáty MeSH
• prekurzory léčiv MeSH
• purinové nukleosidy MeSH
• puriny MeSH
• ribonukleosidy MeSH
• RNA-dependentní RNA-polymerasa MeSH

Emerging flaviviruses are causative agents of severe and life-threatening diseases, against which no approved therapies are available. Among the nucleoside analogues, which represent a promising group of potentially therapeutic compounds, fluorine-substituted nucleosides are characterized by unique structural and functional properties. Despite having first been synthesized almost 5 decades ago, they still offer new therapeutic opportunities as inhibitors of essential viral or cellular enzymes active in nucleic acid replication/transcription or nucleoside/nucleotide metabolism. Here, we report evaluation of the antiflaviviral activity of 28 nucleoside analogues, each modified with a fluoro substituent at different positions of the ribose ring and/or heterocyclic nucleobase. Our antiviral screening revealed that 3'-deoxy-3'-fluoroadenosine exerted a low-micromolar antiviral effect against tick-borne encephalitis virus (TBEV), Zika virus, and West Nile virus (WNV) (EC50 values from 1.1 ± 0.1 μM to 4.7 ± 1.5 μM), which was manifested in host cell lines of neural and extraneural origin. The compound did not display any measurable cytotoxicity up to concentrations of 25 μM but had an observable cytostatic effect, resulting in suppression of cell proliferation at concentrations of >12.5 μM. Novel approaches based on quantitative phase imaging using holographic microscopy were developed for advanced characterization of antiviral and cytotoxic profiles of 3'-deoxy-3'-fluoroadenosine in vitro In addition to its antiviral activity in cell cultures, 3'-deoxy-3'-fluoroadenosine was active in vivo in mouse models of TBEV and WNV infection. Our results demonstrate that fluoro-modified nucleosides represent a group of bioactive molecules with excellent potential to serve as prospective broad-spectrum antivirals in antiviral research and drug development.

• Klíčová slova
• 3′-deoxy-3′-fluoroadenosine, antiviral activity, cytotoxicity, flavivirus, mouse model, nucleoside analogue, tick-borne encephalitis virus,
• MeSH
• antivirové látky farmakologie   MeSH
• deoxyadenosiny farmakologie   MeSH
• infekce virem zika * MeSH
• myši MeSH
• prospektivní studie MeSH
• replikace viru MeSH
• virus zika * MeSH
• viry klíšťové encefalitidy * MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 3'-fluoro-3'-deoxyadenosine MeSH Prohlížeč
• antivirové látky MeSH
• deoxyadenosiny MeSH

We provide here a current overview of marmoset (Callithrix) evolution, hybridization, species biology, basic/biomedical research, and conservation initiatives. Composed of 2 subgroups, the aurita group (C aurita and C flaviceps) and the jacchus group (C geoffroyi, C jacchus, C kuhlii, and C penicillata), this relatively young primate radiation is endemic to the Brazilian Cerrado, Caatinga, and Atlantic Forest biomes. Significant impacts on Callithrix within these biomes resulting from anthropogenic activity include (1) population declines, particularly for the aurita group; (2) widespread geographic displacement, biological invasions, and range expansions of C jacchus and C penicillata; (3) anthropogenic hybridization; and (4) epizootic Yellow Fever and Zika viral outbreaks. A number of Brazilian legal and conservation initiatives are now in place to protect the threatened aurita group and increase research about them. Due to their small size and rapid life history, marmosets are prized biomedical models. As a result, there are increasingly sophisticated genomic Callithrix resources available and burgeoning marmoset functional, immuno-, and epigenomic research. In both the laboratory and the wild, marmosets have given us insight into cognition, social group dynamics, human disease, and pregnancy. Callithrix jacchus and C penicillata are emerging neotropical primate models for arbovirus disease, including Dengue and Zika. Wild marmoset populations are helping us understand sylvatic transmission and human spillover of Zika and Yellow Fever viruses. All of these factors are positioning marmosets as preeminent models to facilitate understanding of facets of evolution, hybridization, conservation, human disease, and emerging infectious diseases.

• Klíčová slova
• Brazil, arbovirus, biological invasion, biomedical, callitrichid, conservation, endangered, hybridization, neotropical, pathogen,
• MeSH
• Callithrix genetika   MeSH
• genomika MeSH
• hybridizace genetická MeSH
• infekce virem zika * MeSH
• virus zika * MeSH
• žlutá zimnice * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Brazílie MeSH

A highly effective way to improve prognosis of viral infectious diseases and to determine the outcome of infection is early, fast, simple, and efficient diagnosis of viral pathogens in biological fluids. Among a wide range of viral pathogens, Flaviviruses attract a special attention. Flavivirus genus includes more than 70 viruses, the most familiar being dengue virus (DENV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV). Haemorrhagic and encephalitis diseases are the most common severe consequences of flaviviral infection. Currently, increasing attention is being paid to the development of electrochemical immunological methods for the determination of Flaviviruses. This review critically compares and evaluates recent research progress in electrochemical biosensing of DENV, ZIKV, and JEV without labelling. Specific attention is paid to comparison of detection strategies, electrode materials, and analytical characteristics. The potential of so far developed biosensors is discussed together with an outlook for further development in this field.

• Klíčová slova
• Flavivirus, electrochemical biosensors, label-free,
• MeSH
• biosenzitivní techniky * MeSH
• dengue * diagnóza   MeSH
• Flavivirus * MeSH
• infekce virem zika * diagnóza   MeSH
• japonská encefalitida * diagnóza   MeSH
• lidé MeSH
• virus zika MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH