Viruses

Editorial

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8 pages, 240 KiB

Open AccessEditorial

The Present and Future of Virology in the Czech Republic—A New Phoenix Made of Ashes?

by Tomas Ruml

Viruses 2022, 14(6), 1303; https://doi.org/10.3390/v14061303 - 14 Jun 2022

Viewed by 2012

Abstract

The Czech Republic, a part of the former Czechoslovakia, has been at the forefront of several research directions in virology, genetics and physiology [...] Full article

(This article belongs to the Special Issue Virology in the Czech Republic – from a Great Legacy to Optimistic Future)

Research

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21 pages, 27561 KiB

Open AccessArticle

Diphyllin Shows a Broad-Spectrum Antiviral Activity against Multiple Medically Important Enveloped RNA and DNA Viruses

by Michal Štefánik, Dattatry Shivajirao Bhosale, Jan Haviernik, Petra Straková, Martina Fojtíková, Lucie Dufková, Ivana Huvarová, Jiří Salát, Jan Bartáček, Jan Svoboda, Miloš Sedlák, Daniel Růžek, Andrew D. Miller and Luděk Eyer

Viruses 2022, 14(2), 354; https://doi.org/10.3390/v14020354 - 9 Feb 2022

Cited by 14 | Viewed by 3470

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Virology in the Czech Republic – from a Great Legacy to Optimistic Future)

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16 pages, 3415 KiB

Open AccessCommunication

One-Enzyme RTX-PCR for the Detection of RNA Viruses from Multiple Virus Genera and Crop Plants

by Hana Hoffmeisterová, Kateřina Kratochvílová, Noemi Čeřovská, Lucie Slavíková, Jakub Dušek, Karel Muller, Jan Fousek, Helena Plchová, Oldřich Navrátil, Jiban Kumar Kundu and Tomáš Moravec

Viruses 2022, 14(2), 298; https://doi.org/10.3390/v14020298 - 31 Jan 2022

Cited by 6 | Viewed by 4824

Abstract

Reverse transcription PCR (RT-PCR) is a popular method for detecting RNA viruses in plants. RT-PCR is usually performed in a classical two-step procedure: in the first step, cDNA is synthesized by reverse transcriptase (RT), followed by PCR amplification by a thermostable polymerase in [...] Read more.

Reverse transcription PCR (RT-PCR) is a popular method for detecting RNA viruses in plants. RT-PCR is usually performed in a classical two-step procedure: in the first step, cDNA is synthesized by reverse transcriptase (RT), followed by PCR amplification by a thermostable polymerase in a separate tube in the second step. However, one-step kits containing multiple enzymes optimized for RT and PCR amplification in a single tube can also be used. Here, we describe an RT-PCR single-enzyme assay based on an RTX DNA polymerase that has both RT and polymerase activities. The expression plasmid pET_RTX_(exo-) was transferred to various E. coli genotypes that either compensated for codon bias (Rosetta-gami 2) or contained additional chaperones to promote solubility (BL21 (DE3) with plasmids pKJE8 or pTf2). The RTX enzyme was then purified and used for the RT-PCR assay. Several purified plant viruses (TMV, PVX, and PVY) were used to determine the efficiency of the assay compared to a commercial one-step RT-PCR kit. The RT-PCR assay with the RTX enzyme was validated for the detection of viruses from different genera using both total RNA and crude sap from infected plants. The detection endpoint of RTX-PCR for purified TMV was estimated to be approximately 0.01 pg of the whole virus per 25 µL reaction, corresponding to 6 virus particles/µL. Interestingly, the endpoint for detection of TMV from crude sap was also 0.01 pg per reaction in simulated crude plant extracts. The longest RNA fragment that could be amplified in a one-tube arrangement was 2379 bp long. The longest DNA fragment that could be amplified during a 10s extension was 6899 bp long. In total, we were able to detect 13 viruses from 11 genera using RTX-PCR. For each virus, two to three specific fragments were amplified. The RT-PCR assay using the RTX enzyme described here is a very robust, inexpensive, rapid, easy to perform, and sensitive single-enzyme assay for the detection of plant viruses. Full article

(This article belongs to the Special Issue Virology in the Czech Republic – from a Great Legacy to Optimistic Future)

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22 pages, 4569 KiB

Open AccessArticle

Fullerene Derivatives Prevent Packaging of Viral Genomic RNA into HIV-1 Particles by Binding Nucleocapsid Protein

by Ivana Křížová, Alžběta Dostálková, Edison Castro, Jan Prchal, Romana Hadravová, Filip Kaufman, Richard Hrabal, Tomáš Ruml, Manuel Llano, Luis Echegoyen and Michaela Rumlová

Viruses 2021, 13(12), 2451; https://doi.org/10.3390/v13122451 - 6 Dec 2021

Cited by 4 | Viewed by 3096 | Correction

Abstract

Fullerene derivatives with hydrophilic substituents have been shown to exhibit a range of biological activities, including antiviral ones. For a long time, the anti-HIV activity of fullerene derivatives was believed to be due to their binding into the hydrophobic pocket of HIV-1 protease, [...] Read more.

Fullerene derivatives with hydrophilic substituents have been shown to exhibit a range of biological activities, including antiviral ones. For a long time, the anti-HIV activity of fullerene derivatives was believed to be due to their binding into the hydrophobic pocket of HIV-1 protease, thereby blocking its activity. Recent work, however, brought new evidence of a novel, protease-independent mechanism of fullerene derivatives’ action. We studied in more detail the mechanism of the anti-HIV-1 activity of N,N-dimethyl[70]fulleropyrrolidinium iodide fullerene derivatives. By using a combination of in vitro and cell-based approaches, we showed that these C₇₀ derivatives inhibited neither HIV-1 protease nor HIV-1 maturation. Instead, our data indicate effects of fullerene C₇₀ derivatives on viral genomic RNA packaging and HIV-1 cDNA synthesis during reverse transcription—without impairing reverse transcriptase activity though. Molecularly, this could be explained by a strong binding affinity of these fullerene derivatives to HIV-1 nucleocapsid domain, preventing its proper interaction with viral genomic RNA, thereby blocking reverse transcription and HIV-1 infectivity. Moreover, the fullerene derivatives’ oxidative activity and fluorescence quenching, which could be one of the reasons for the inconsistency among reported anti-HIV-1 mechanisms, are discussed herein. Full article

(This article belongs to the Special Issue Virology in the Czech Republic – from a Great Legacy to Optimistic Future)

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24 pages, 5873 KiB

Open AccessArticle

ATM-Dependent Phosphorylation of Hepatitis B Core Protein in Response to Genotoxic Stress

by Barbora Lubyova, Eva Tikalova, Kristyna Krulova, Jan Hodek, Ales Zabransky, Ivan Hirsch and Jan Weber

Viruses 2021, 13(12), 2438; https://doi.org/10.3390/v13122438 - 5 Dec 2021

Cited by 3 | Viewed by 3526

Abstract

Chronic hepatitis caused by infection with the Hepatitis B virus is a life-threatening condition. In fact, 1 million people die annually due to liver cirrhosis or hepatocellular carcinoma. Recently, several studies demonstrated a molecular connection between the host DNA damage response (DDR) pathway [...] Read more.

Chronic hepatitis caused by infection with the Hepatitis B virus is a life-threatening condition. In fact, 1 million people die annually due to liver cirrhosis or hepatocellular carcinoma. Recently, several studies demonstrated a molecular connection between the host DNA damage response (DDR) pathway and HBV replication and reactivation. Here, we investigated the role of Ataxia-telangiectasia-mutated (ATM) and Ataxia telangiectasia and Rad3-related (ATR) PI3-kinases in phosphorylation of the HBV core protein (HBc). We determined that treatment of HBc-expressing hepatocytes with genotoxic agents, e.g., etoposide or hydrogen peroxide, activated the host ATM-Chk2 pathway, as determined by increased phosphorylation of ATM at Ser1981 and Chk2 at Thr68. The activation of ATM led, in turn, to increased phosphorylation of cytoplasmic HBc at serine-glutamine (SQ) motifs located in its C-terminal domain. Conversely, down-regulation of ATM using ATM-specific siRNAs or inhibitor effectively reduced etoposide-induced HBc phosphorylation. Detailed mutation analysis of S-to-A HBc mutants revealed that S170 (S168 in a 183-aa HBc variant) is the primary site targeted by ATM-regulated phosphorylation. Interestingly, mutation of two major phosphorylation sites involving serines at positions 157 and 164 (S155 and S162 in a 183-aa HBc variant) resulted in decreased etoposide-induced phosphorylation, suggesting that the priming phosphorylation at these serine-proline (SP) sites is vital for efficient phosphorylation of SQ motifs. Notably, the mutation of S172 (S170 in a 183-aa HBc variant) had the opposite effect and resulted in massively up-regulated phosphorylation of HBc, particularly at S170. Etoposide treatment of HBV infected HepG2-NTCP cells led to increased levels of secreted HBe antigen and intracellular HBc protein. Together, our studies identified HBc as a substrate for ATM-mediated phosphorylation and mapped the phosphorylation sites. The increased expression of HBc and HBe antigens in response to genotoxic stress supports the idea that the ATM pathway may provide growth advantage to the replicating virus. Full article

(This article belongs to the Special Issue Virology in the Czech Republic – from a Great Legacy to Optimistic Future)

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15 pages, 3786 KiB

Open AccessEditor’s ChoiceArticle

Analyses of Leishmania-LRV Co-Phylogenetic Patterns and Evolutionary Variability of Viral Proteins

by Alexei Y. Kostygov, Danyil Grybchuk, Yulia Kleschenko, Daniil S. Chistyakov, Alexander N. Lukashev, Evgeny S. Gerasimov and Vyacheslav Yurchenko

Viruses 2021, 13(11), 2305; https://doi.org/10.3390/v13112305 - 19 Nov 2021

Cited by 17 | Viewed by 3244

Abstract

Leishmania spp. are important pathogens causing a vector-borne disease with a broad range of clinical manifestations from self-healing ulcers to the life-threatening visceral forms. Presence of Leishmania RNA virus (LRV) confers survival advantage to these parasites by suppressing anti-leishmanial immunity in the vertebrate [...] Read more.

Leishmania spp. are important pathogens causing a vector-borne disease with a broad range of clinical manifestations from self-healing ulcers to the life-threatening visceral forms. Presence of Leishmania RNA virus (LRV) confers survival advantage to these parasites by suppressing anti-leishmanial immunity in the vertebrate host. The two viral species, LRV1 and LRV2 infect species of the subgenera Viannia and Leishmania, respectively. In this work we investigated co-phylogenetic patterns of leishmaniae and their viruses on a small scale (LRV2 in L. major) and demonstrated their predominant coevolution, occasionally broken by intraspecific host switches. Our analysis of the two viral genes, encoding the capsid and RNA-dependent RNA polymerase (RDRP), revealed them to be under the pressure of purifying selection, which was considerably stronger for the former gene across the whole tree. The selective pressure also differs between the LRV clades and correlates with the frequency of interspecific host switches. In addition, using experimental (capsid) and predicted (RDRP) models we demonstrated that the evolutionary variability across the structure is strikingly different in these two viral proteins. Full article

(This article belongs to the Special Issue Virology in the Czech Republic – from a Great Legacy to Optimistic Future)

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12 pages, 1864 KiB

Open AccessArticle

Repeated MDA5 Gene Loss in Birds: An Evolutionary Perspective

by Veronika Krchlíková, Tomáš Hron, Martin Těšický, Tao Li, Jiří Hejnar, Michal Vinkler and Daniel Elleder

Viruses 2021, 13(11), 2131; https://doi.org/10.3390/v13112131 - 22 Oct 2021

Cited by 9 | Viewed by 3144

Abstract

Two key cytosolic receptors belonging to the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family sense the viral RNA-derived danger signals: RIG-I and melanoma differentiation-associated protein 5 (MDA5). Their activation establishes an antiviral state by downstream signaling that ultimately activates interferon-stimulated genes (ISGs). [...] Read more.

Two key cytosolic receptors belonging to the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family sense the viral RNA-derived danger signals: RIG-I and melanoma differentiation-associated protein 5 (MDA5). Their activation establishes an antiviral state by downstream signaling that ultimately activates interferon-stimulated genes (ISGs). While in rare cases RIG-I gene loss has been detected in mammalian and avian species, most notably in the chicken, MDA5 pseudogenization has only been detected once in mammals. We have screened over a hundred publicly available avian genome sequences and describe an independent disruption of MDA5 in two unrelated avian lineages, the storks (Ciconiiformes) and the rallids (Gruiformes). The results of our RELAX analysis confirmed the absence of negative selection in the MDA5 pseudogene. In contrast to our prediction, we have shown, using multiple dN/dS-based approaches, that the MDA5 loss does not appear to have resulted in any compensatory evolution in the RIG-I gene, which may partially share its ligand-binding specificity. Together, our results indicate that the MDA5 pseudogenization may have important functional effects on immune responsiveness in these two avian clades. Full article

(This article belongs to the Special Issue Virology in the Czech Republic – from a Great Legacy to Optimistic Future)

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12 pages, 1362 KiB

Open AccessArticle

Experimental and Natural Infections of Tick-Borne Encephalitis Virus in Dogs

by Jiri Salat, Milan Hunady, Pavel Schanilec, Petra Strakova, Michal Stefanik, Pavel Svoboda, Lucie Strelcova, Jana Bojcukova, Martin Palus and Daniel Růžek

Viruses 2021, 13(10), 2039; https://doi.org/10.3390/v13102039 - 9 Oct 2021

Cited by 7 | Viewed by 2677

Abstract

Dogs are frequently infected with the tick-borne encephalitis virus (TBEV). However, to date, only a few clinically manifest cases of tick-borne encephalitis (TBE) have been reported in dogs. In this study, three-month-old beagle dogs were infected with TBEV through a subcutaneous injection. Body [...] Read more.

Dogs are frequently infected with the tick-borne encephalitis virus (TBEV). However, to date, only a few clinically manifest cases of tick-borne encephalitis (TBE) have been reported in dogs. In this study, three-month-old beagle dogs were infected with TBEV through a subcutaneous injection. Body temperature, clinical signs, blood haematology, blood biochemistry, and immune responses were monitored for up to 28 days postinfection (p.i.). No changes in body temperature or clinical signs were observed in the infected dogs. Most haematology and blood biochemistry parameters were unchanged after the infection, except for a slight reduction in blood lymphocyte counts, but they were within the physiological range. Low-titre viraemia was detected in 2/4 infected dogs between days 1 and 3 p.i. All infected dogs developed a robust immune response, in terms of neutralising antibodies. Thus, TBEV infections lead to effective seroconversion in dogs. Next, to assess TBEV exposure in dogs in the TBEV-endemic region of the Czech Republic, we conducted a serosurvey. Virus neutralisation tests revealed TBEV-specific antibodies in 17 of 130 (13.07%) healthy dogs, which confirmed a high, but clinically inappreciable TBEV exposure rate in the endemic area. The seropositivity rate was similar (12.7%; 41 positives out of 323) in a subgroup of dogs with various clinical disorders, and it was 13.4% (23 out of 171) in a subgroup of dogs with signs of acute neurological disease. Two dogs with fatal acute meningoencephalitis showed positive results for TBEV-specific IgM and IgG antibodies. These data extended our understanding of the clinical presentation of TBEV infections. Full article

(This article belongs to the Special Issue Virology in the Czech Republic – from a Great Legacy to Optimistic Future)

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20 pages, 2829 KiB

Open AccessArticle

Vaccinia Virus Expressing Interferon Regulatory Factor 3 Induces Higher Protective Immune Responses against Lethal Poxvirus Challenge in Atopic Organism

by Hana Pilna, Vera Hajkova, Jarmila Knitlova, Jana Liskova, Jana Elsterova and Zora Melkova

Viruses 2021, 13(10), 1986; https://doi.org/10.3390/v13101986 - 3 Oct 2021

Cited by 2 | Viewed by 2507

Abstract

Vaccinia virus (VACV) is an enveloped DNA virus from the Orthopoxvirus family, various strains of which were used in the successful eradication campaign against smallpox. Both original and newer VACV-based replicating vaccines reveal a risk of serious complications in atopic individuals. VACV encodes [...] Read more.

Vaccinia virus (VACV) is an enveloped DNA virus from the Orthopoxvirus family, various strains of which were used in the successful eradication campaign against smallpox. Both original and newer VACV-based replicating vaccines reveal a risk of serious complications in atopic individuals. VACV encodes various factors interfering with host immune responses at multiple levels. In atopic skin, the production of type I interferon is compromised, while VACV specifically inhibits the phosphorylation of the Interferon Regulatory Factor 3 (IRF-3) and expression of interferons. To overcome this block, we generated a recombinant VACV-expressing murine IRF-3 (WR-IRF3) and characterized its effects on virus growth, cytokine expression and apoptosis in tissue cultures and in spontaneously atopic Nc/Nga and control Balb/c mice. Further, we explored the induction of protective immune responses against a lethal dose of wild-type WR, the surrogate of smallpox. We demonstrate that the overexpression of IRF-3 by WR-IRF3 increases the expression of type I interferon, modulates the expression of several cytokines and induces superior protective immune responses against a lethal poxvirus challenge in both Nc/Nga and Balb/c mice. Additionally, the results may be informative for design of other virus-based vaccines or for therapy of different viral infections. Full article

(This article belongs to the Special Issue Virology in the Czech Republic – from a Great Legacy to Optimistic Future)

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12 pages, 1887 KiB

Open AccessArticle

Substrate Specificity of SARS-CoV-2 Nsp10-Nsp16 Methyltransferase

by Roberto Benoni, Petra Krafcikova, Marek R. Baranowski, Joanna Kowalska, Evzen Boura and Hana Cahová

Viruses 2021, 13(9), 1722; https://doi.org/10.3390/v13091722 - 30 Aug 2021

Cited by 21 | Viewed by 4553

Abstract

The ongoing COVID-19 pandemic exemplifies the general need to better understand viral infections. The positive single-strand RNA genome of its causative agent, the SARS coronavirus 2 (SARS-CoV-2), encodes all viral enzymes. In this work, we focused on one particular methyltransferase (MTase), nsp16, which, [...] Read more.

The ongoing COVID-19 pandemic exemplifies the general need to better understand viral infections. The positive single-strand RNA genome of its causative agent, the SARS coronavirus 2 (SARS-CoV-2), encodes all viral enzymes. In this work, we focused on one particular methyltransferase (MTase), nsp16, which, in complex with nsp10, is capable of methylating the first nucleotide of a capped RNA strand at the 2′-O position. This process is part of a viral capping system and is crucial for viral evasion of the innate immune reaction. In light of recently discovered non-canonical RNA caps, we tested various dinucleoside polyphosphate-capped RNAs as substrates for nsp10-nsp16 MTase. We developed an LC-MS-based method and discovered four types of capped RNA (m⁷Gp₃A(G)- and Gp₃A(G)-RNA) that are substrates of the nsp10-nsp16 MTase. Our technique is an alternative to the classical isotope labelling approach for the measurement of 2′-O-MTase activity. Further, we determined the IC₅₀ value of sinefungin to illustrate the use of our approach for inhibitor screening. In the future, this approach may be an alternative technique to the radioactive labelling method for screening inhibitors of any type of 2′-O-MTase. Full article

(This article belongs to the Special Issue Virology in the Czech Republic – from a Great Legacy to Optimistic Future)

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10 pages, 2617 KiB

Open AccessArticle

Localization of SARS-CoV-2 Capping Enzymes Revealed by an Antibody against the nsp10 Subunit

by Vladimira Horova, Barbora Landova, Jan Hodek, Karel Chalupsky, Petra Krafcikova, Dominika Chalupska, Vojtech Duchoslav, Jan Weber, Evzen Boura and Martin Klima

Viruses 2021, 13(8), 1487; https://doi.org/10.3390/v13081487 - 29 Jul 2021

Cited by 10 | Viewed by 2916

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease-19 pandemic. One of the key components of the coronavirus replication complex are the RNA methyltransferases (MTases), RNA-modifying enzymes crucial for RNA cap formation. Recently, the structure of the [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease-19 pandemic. One of the key components of the coronavirus replication complex are the RNA methyltransferases (MTases), RNA-modifying enzymes crucial for RNA cap formation. Recently, the structure of the 2’-O MTase has become available; however, its biological characterization within the infected cells remains largely elusive. Here, we report a novel monoclonal antibody directed against the SARS-CoV-2 non-structural protein nsp10, a subunit of both the 2’-O RNA and N7 MTase protein complexes. Using this antibody, we investigated the subcellular localization of the SARS-CoV-2 MTases in cells infected with the SARS-CoV-2. Full article

(This article belongs to the Special Issue Virology in the Czech Republic – from a Great Legacy to Optimistic Future)

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14 pages, 6898 KiB

Open AccessArticle

Novel Viruses That Lyse Plant and Human Strains of Kosakonia cowanii

by Karel Petrzik, Sára Brázdová and Krzysztof Krawczyk

Viruses 2021, 13(8), 1418; https://doi.org/10.3390/v13081418 - 21 Jul 2021

Cited by 11 | Viewed by 3038

Abstract

Kosakonia cowanii (syn. Enterobacter cowanii) is a highly competitive bacterium that lives with plant, insect, fish, bird, and human organisms. It is pathogenic on some plants and an opportunistic pathogen of human. Nine novel viruses that lyse plant pathogenic strains and/or human [...] Read more.

Kosakonia cowanii (syn. Enterobacter cowanii) is a highly competitive bacterium that lives with plant, insect, fish, bird, and human organisms. It is pathogenic on some plants and an opportunistic pathogen of human. Nine novel viruses that lyse plant pathogenic strains and/or human strains of K. cowanii were isolated, sequenced, and characterized. Kc166A is a novel kayfunavirus, Kc261 is a novel bonnellvirus, and Kc318 is a new cronosvirus (all Autographiviridae). Kc237 is a new sortsnevirus, but Kc166B and Kc283 are members of new genera within Podoviridae. Kc304 is a new winklervirus, and Kc263 and Kc305 are new myoviruses. The viruses differ in host specificity, plaque phenotype, and lysis kinetics. Some of them should be suitable also as pathogen control agents. Full article

(This article belongs to the Special Issue Virology in the Czech Republic – from a Great Legacy to Optimistic Future)

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9 pages, 253 KiB

Open AccessArticle

Five Antigen Tests for SARS-CoV-2: Virus Viability Matters

by Miroslav Homza, Hana Zelena, Jaroslav Janosek, Hana Tomaskova, Eduard Jezo, Alena Kloudova, Jakub Mrazek, Zdenek Svagera and Roman Prymula

Viruses 2021, 13(4), 684; https://doi.org/10.3390/v13040684 - 15 Apr 2021

Cited by 27 | Viewed by 9593

Abstract

Antigen testing for SARS-CoV-2 (AGT) is generally considered inferior to RT-PCR testing in terms of sensitivity. However, little is known about the infectiousness of RT-PCR positive patients who pass undetected by AGT. In a screening setting for mildly symptomatic or asymptomatic patients with [...] Read more.

Antigen testing for SARS-CoV-2 (AGT) is generally considered inferior to RT-PCR testing in terms of sensitivity. However, little is known about the infectiousness of RT-PCR positive patients who pass undetected by AGT. In a screening setting for mildly symptomatic or asymptomatic patients with high COVID-19 prevalence (30–40%), 1141 patients were tested using one of five AGTs and RT-PCR. Where the results differed, virus viability in the samples was tested on cell culture (CV-1 cells). The test battery included AGTs by JOYSBIO, Assure Tech, SD Biosensor, VivaChek Biotech and NDFOS. Sensitivities of the ATGs compared to RT-PCR ranged from 42% to 76%. The best test yielded a 76% sensitivity, 97% specificity, 92% positive, and 89% negative predictive values, respectively. However, in the best performing ATG tests, almost 90% of samples with “false negative” AGT results contained no viable virus. Corrected on the virus viability, sensitivities grew to 81–97% and, with one exception, the tests yielded high specificities >96%. Performance characteristics of the best test after adjustment were 96% sensitivity, 97% specificity, 92% positive, and 99% negative predictive values (high prevalence population). We, therefore, believe that virus viability should be considered when assessing the AGT performance. Also, our results indicate that a well-performing antigen test could in a high-prevalence setting serve as an excellent tool for identifying patients shedding viable virus. We also propose that the high proportion of RT-PCR-positive samples containing no viable virus in the group of “false negatives” of the antigen test should be further investigated with the aim of possibly preventing needless isolation of such patients. Full article

(This article belongs to the Special Issue Virology in the Czech Republic – from a Great Legacy to Optimistic Future)

Review

Jump to: Editorial, Research, Other

19 pages, 1483 KiB

Open AccessReview

Flavonoids Target Human Herpesviruses That Infect the Nervous System: Mechanisms of Action and Therapeutic Insights

by Miroslava Šudomová, Kateřina Berchová-Bímová, Alena Mazurakova, Dunja Šamec, Peter Kubatka and Sherif T. S. Hassan

Viruses 2022, 14(3), 592; https://doi.org/10.3390/v14030592 - 13 Mar 2022

Cited by 27 | Viewed by 6741

Abstract

Human herpesviruses (HHVs) are large DNA viruses with highly infectious characteristics. HHVs can induce lytic and latent infections in their host, and most of these viruses are neurotropic, with the capacity to generate severe and chronic neurological diseases of the peripheral nervous system [...] Read more.

Human herpesviruses (HHVs) are large DNA viruses with highly infectious characteristics. HHVs can induce lytic and latent infections in their host, and most of these viruses are neurotropic, with the capacity to generate severe and chronic neurological diseases of the peripheral nervous system (PNS) and central nervous system (CNS). Treatment of HHV infections based on strategies that include natural products-derived drugs is one of the most rapidly developing fields of modern medicine. Therefore, in this paper, we lend insights into the recent advances that have been achieved during the past five years in utilizing flavonoids as promising natural drugs for the treatment of HHVs infections of the nervous system such as alpha-herpesviruses (herpes simplex virus type 1, type 2, and varicella-zoster virus), beta-herpesviruses (human cytomegalovirus), and gamma-herpesviruses (Epstein–Barr virus and Kaposi sarcoma-associated herpesvirus). The neurological complications associated with infections induced by the reviewed herpesviruses are emphasized. Additionally, this work covers all possible mechanisms and pathways by which flavonoids induce promising therapeutic actions against the above-mentioned herpesviruses. Full article

(This article belongs to the Special Issue Virology in the Czech Republic – from a Great Legacy to Optimistic Future)

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44 pages, 12869 KiB

Open AccessReview

Targeting the Virus Capsid as a Tool to Fight RNA Viruses

by Lucie Hozáková, Barbora Vokatá, Tomáš Ruml and Pavel Ulbrich

Viruses 2022, 14(2), 174; https://doi.org/10.3390/v14020174 - 18 Jan 2022

Cited by 6 | Viewed by 3332

Abstract

Several strategies have been developed to fight viral infections, not only in humans but also in animals and plants. Some of them are based on the development of efficient vaccines, to target the virus by developed antibodies, others focus on finding antiviral compounds [...] Read more.

Several strategies have been developed to fight viral infections, not only in humans but also in animals and plants. Some of them are based on the development of efficient vaccines, to target the virus by developed antibodies, others focus on finding antiviral compounds with activities that inhibit selected virus replication steps. Currently, there is an increasing number of antiviral drugs on the market; however, some have unpleasant side effects, are toxic to cells, or the viruses quickly develop resistance to them. As the current situation shows, the combination of multiple antiviral strategies or the combination of the use of various compounds within one strategy is very important. The most desirable are combinations of drugs that inhibit different steps in the virus life cycle. This is an important issue especially for RNA viruses, which replicate their genomes using error-prone RNA polymerases and rapidly develop mutants resistant to applied antiviral compounds. Here, we focus on compounds targeting viral structural capsid proteins, thereby inhibiting virus assembly or disassembly, virus binding to cellular receptors, or acting by inhibiting other virus replication mechanisms. This review is an update of existing papers on a similar topic, by focusing on the most recent advances in the rapidly evolving research of compounds targeting capsid proteins of RNA viruses. Full article

(This article belongs to the Special Issue Virology in the Czech Republic – from a Great Legacy to Optimistic Future)

34 pages, 580 KiB

Open AccessReview

History of Arbovirus Research in the Czech Republic

by Zdenek Hubálek

Viruses 2021, 13(11), 2334; https://doi.org/10.3390/v13112334 - 22 Nov 2021

Cited by 8 | Viewed by 3567

Abstract

The aim of this review is to follow the history of studies on endemiv arboviruses and the diseases they cause which were detected in the Czech lands (Bohemia, Moravia and Silesia (i.e., the Czech Republic)). The viruses involve tick-borne encephalitis, West Nile and [...] Read more.

The aim of this review is to follow the history of studies on endemiv arboviruses and the diseases they cause which were detected in the Czech lands (Bohemia, Moravia and Silesia (i.e., the Czech Republic)). The viruses involve tick-borne encephalitis, West Nile and Usutu flaviviruses; the Sindbis alphavirus; Ťahyňa, Batai, Lednice and Sedlec bunyaviruses; the Uukuniemi phlebovirus; and the Tribeč orbivirus. Arboviruses temporarily imported from abroad to the Czech Republic have been omitted. This brief historical review includes a bibliography of all relevant papers. Full article

(This article belongs to the Special Issue Virology in the Czech Republic – from a Great Legacy to Optimistic Future)

24 pages, 4022 KiB

Open AccessReview

Precursors of Viral Proteases as Distinct Drug Targets

by Taťána Majerová and Pavel Novotný

Viruses 2021, 13(10), 1981; https://doi.org/10.3390/v13101981 - 2 Oct 2021

Cited by 16 | Viewed by 4554

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Virology in the Czech Republic – from a Great Legacy to Optimistic Future)

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4 pages, 1380 KiB

Open AccessCorrection

Correction: Křížová et al. Fullerene Derivatives Prevent Packaging of Viral Genomic RNA into HIV-1 Particles by Binding Nucleocapsid Protein. Viruses 2021, 13, 2451

by Ivana Křížová, Alžběta Dostálková, Edison Castro, Jan Prchal, Romana Hadravová, Filip Kaufman, Richard Hrabal, Tomáš Ruml, Manuel Llano, Luis Echegoyen and Michaela Rumlová

Viruses 2022, 14(6), 1187; https://doi.org/10.3390/v14061187 - 30 May 2022

Viewed by 1435

Abstract

The authors wish to make the following corrections to this paper [...] Full article

(This article belongs to the Special Issue Virology in the Czech Republic – from a Great Legacy to Optimistic Future)

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10 pages, 1473 KiB

Open AccessBrief Report

Non-Nucleotide RNA-Dependent RNA Polymerase Inhibitor That Blocks SARS-CoV-2 Replication

by Milan Dejmek, Eva Konkoľová, Luděk Eyer, Petra Straková, Pavel Svoboda, Michal Šála, Kateřina Krejčová, Daniel Růžek, Evzen Boura and Radim Nencka

Viruses 2021, 13(8), 1585; https://doi.org/10.3390/v13081585 - 11 Aug 2021

Cited by 26 | Viewed by 5273

Abstract

SARS-CoV-2 has caused an extensive pandemic of COVID-19 all around the world. Key viral enzymes are suitable molecular targets for the development of new antivirals against SARS-CoV-2 which could represent potential treatments of the corresponding disease. With respect to its essential role in [...] Read more.

SARS-CoV-2 has caused an extensive pandemic of COVID-19 all around the world. Key viral enzymes are suitable molecular targets for the development of new antivirals against SARS-CoV-2 which could represent potential treatments of the corresponding disease. With respect to its essential role in the replication of viral RNA, RNA-dependent RNA polymerase (RdRp) is one of the prime targets. HeE1-2Tyr and related derivatives were originally discovered as inhibitors of the RdRp of flaviviruses. Here, we present that these pyridobenzothiazole derivatives also significantly inhibit SARS-CoV-2 RdRp, as demonstrated using both polymerase- and cell-based antiviral assays. Full article

(This article belongs to the Special Issue Virology in the Czech Republic – from a Great Legacy to Optimistic Future)

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