VirusDisease最新文献

{"title":"Molecular analysis of 4/91-like variants of avian infectious bronchitis virus (IBV) obtained after the introduction of a 4/91 live-attenuated vaccine in Costa Rica during 2017.","authors":"Mónica Vallejo-Arróliga, Ricardo A Villalobos-Agüero, Rebeca Zamora-Sanabria, James Karkashian-Córdoba","doi":"10.1007/s13337-025-00910-4","DOIUrl":"https://doi.org/10.1007/s13337-025-00910-4","url":null,"abstract":"<p><p>Avian infectious bronchitis virus (IBV) belongs to family <i>Coronaviridae</i>, genus <i>Gammacoronavirus</i> and is one of the most predominant causes of respiratory disease in poultry. Its high mutation rate constantly leads to the emergence of novel variants that complicate disease control. In 2016, a GA13-like IBV outbreak occurred in Costa Rica, prompting the introduction of the 4/91 live-attenuated vaccine. The objective of this research was to perform a molecular characterization of IBV variants circulating in the country six years after the introduction of the 4/91 vaccine. A total of 177 samples from symptomatic birds were analyzed, with 43 testing positive for IBV. Seven complete S1 sequences were obtained and clustered within the GI-13 lineage by phylogenetic analysis. Sequence analysis showed high genetic similarity to the 4/91 vaccine strain, with nucleotide and amino acid sequence identities over 99.13% and 97.96%, respectively, despite these samples being taken from unvaccinated birds. Post-translational modification analysis of the S1 protein revealed conserved N-glycosylation and palmitoylation sites, while two serine phosphorylation changes were predicted between the obtained sequences and the vaccine strain. Selective pressure analysis identified 10 sites under positive selection, mainly located within the receptor-binding domain and hypervariable regions of the S1 subunit. The presence of 4/91-like variants in unvaccinated birds needs attention, and its relation to observed pathology requires further research. Continuous surveillance is essential to monitor for potential vaccine escape mutants and mitigate their impact.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13337-025-00910-4.</p>","PeriodicalId":23708,"journal":{"name":"VirusDisease","volume":"36 1","pages":"81-92"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12021757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accessory viral protein, V, of Newcastle Disease Virus binds dsRNA to facilitate immune evasion.","authors":"Sunny Deval, Vaishnavi Senthil Nathan, Sangita Venkataraman, P L Rao, Prajna Parimita Kar, Anand Srivastava, Madhuri Subbiah","doi":"10.1007/s13337-024-00908-4","DOIUrl":"https://doi.org/10.1007/s13337-024-00908-4","url":null,"abstract":"<p><p>Newcastle disease virus (NDV) is an avian paramyxovirus known to infect more than 250 bird species across the globe. NDV is enveloped and carries a negative-sense RNA genome that codes for six structural proteins and two accessory proteins expressed through a unique co-transcriptional RNA editing mechanism. One of the accessory viral proteins, V protein, is multifunctional and a well-known interferon (IFN) antagonist. The overexpression of V protein is known to enhance viral production kinetics during NDV infection. In this study, we elucidated the events that lead to this augmented viral replication. The V protein overexpression downregulated the expression of host RNA sensor, namely MDA5. Furthermore, during the over-expression of V protein in NDV infected cells, the V protein aggregated in the perinuclear region, co-localizing and binding with the replicating dsRNA. Our structural studies and in silico predictions suggest that V protein binding with dsRNA interferes and competes with MDA5 for binding to dsRNA, eventually disrupting the IFN induction and facilitating the viral replication. This study reports a novel mechanism of host immune evasion by the accessory V protein.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13337-024-00908-4.</p>","PeriodicalId":23708,"journal":{"name":"VirusDisease","volume":"36 1","pages":"68-80"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12022205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In-silico prediction of coat protein structure of Indian citrus ringspot virus and their interactions with the Argonaut2/DCL4 proteins.","authors":"Aniket Angira, Siddharth Yadav, Puniti Mathur, V K Baranwal, Aashish Ranjan, Nandlal Choudhary","doi":"10.1007/s13337-024-00904-8","DOIUrl":"https://doi.org/10.1007/s13337-024-00904-8","url":null,"abstract":"<p><p>The RNA silencing mechanism is a crucial regulatory system in plants, particularly in antiviral defense. However, most of the plant viruses encode a specific protein called RNA silencing suppressor protein that suppress the RNA silencing mechanism of host. This study employs the bioinformatics tools, including SWISS homology model and I-TASSER, to predict the coat protein (CP) tertiary structure of Indian citrus ringspot virus (ICRSV). Then, five protein-protein docking servers (GRAMM, pyDockWEB, HawkDock, ZDOCK and ClusPro) were utilized to investigate interactions of CP of ICRSV with Argonaut2/Dicer-Like (DCL4) protein 4 of RNA silencing pathway of host. In blind docking experiments, the CP consistently engaged in docking interactions with DCL4, while with AGO2, it interacted near the PIWI and MID domains. The AGO2-CP cluster demonstrated 4 salt bridges, 30 hydrogen bonds, and 328 non-bonded contacts, with interface areas spanning 2529 in AGO2 and 2424 in CP, involving 50 and 51 interface residues, respectively. Similarly, the DCL4-CP cluster showed 5 hydrogen bonds and 122 non-bonded contacts, with interface areas spanning 965 in DCL4 and 987 in CP, involving 16 and 19 interface residues, respectively. The established phenomenon of CP interaction with AGO2/DCL4, may resulting in the inhibition of the RNA silencing mechanism and shedding light on the suppression mechanisms of host defense responses.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13337-024-00904-8.</p>","PeriodicalId":23708,"journal":{"name":"VirusDisease","volume":"36 1","pages":"31-40"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12022189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure-based drug designing for potential antiviral activity of selected natural product against Monkeypox (Mpox) virus and its host targets.","authors":"Vimal K Maurya, Swatantra Kumar, Shivani Maurya, Saniya Ansari, Janusz T Paweska, Ahmed S Abdel-Moneim, Shailendra K Saxena","doi":"10.1007/s13337-024-00900-y","DOIUrl":"10.1007/s13337-024-00900-y","url":null,"abstract":"<p><p><i>Monkeypox virus</i> (MPV/MPXV/hMPXV) is a zoonotic infection that is a causative agent of monkeypox disease, which is mainly endemic in West and Central Africa regions, but recent trends suggested that the virus is transmitted around 116 countries worldwide and is still spreading in multiple non-endemic countries, causing global outbreaks. The current therapeutic options for Mpox are limited, with the WHO temporarily recommending smallpox drugs. This suggests an urgent need to discover new therapeutics that may target both viral and host markers involved in the virus life cycle. Curcumin, a polyphenolic natural compound, has broad-spectrum pharmacological activity in both DNA and RNA viruses. Therefore, this study was planned to evaluate the antiviral properties of curcumin against MPXV proteins as well as induced host targets using computational approaches, such as gene target identification, PPI network analysis, antiviral activity prediction, and molecular docking. Our network pharmacology and docking results demonstrated that curcumin majorly targets Mpox DNA polymerase holoenzyme, Methyltransferase VP39, A42R profilin-like protein, envelope protein E8, and TNF, MAPK, NFKB1, and PTGS2 to regulate host inflammatory pathways such as TNF, NF-κB, and MAPK signaling during Mpox infection. Further, we found that curcumin has a strong binding affinity toward the DNA polymerase of MPXV compared to Cidofovir, an approved inhibitor of DNA polymerase. Collectively, our findings suggested that curcumin may have potential use as a multi-targeted antiviral agent against emerging Mpox, encouraging future research that provides the molecular basis for exploring the role of curcumin as a broad-spectrum antiviral agent during viral outbreaks.</p><p><strong>Graphical abstract: </strong>The ligand binding site of MPXV DNA polymerase shows the molecular interactions with curcumin and amino acids present on the active site of the protein.</p>","PeriodicalId":23708,"journal":{"name":"VirusDisease","volume":"35 4","pages":"589-608"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11635075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variation in seed transmission of cowpea viruses between single and multiple infections.","authors":"K E Ogunsola, P Lava Kumar","doi":"10.1007/s13337-024-00899-2","DOIUrl":"10.1007/s13337-024-00899-2","url":null,"abstract":"<p><p>Seed transmission (ST) plays an important role in virus dispersion and disease epidemiology. Many viruses infecting cowpea are known to be seed-transmitted. This study evaluated the rate of virus ST in cowpea varieties inoculated under screenhouse conditions (SC) with bean common mosaic virus-blackeye cowpea mosaic strain (BCMV-BlCM), Southern bean mosaic virus (SBMV) and cucumber mosaic virus (CMV) under single and multiple-infections. Up to 50 seeds harvested from the virus-infected plants of each variety per treatment were used for the grow-out test under insect-proof SC. Data were recorded on seed germination (SG), symptoms in seedlings, and virus ST. The leaf samples were tested for viruses by enzyme-linked immunosorbent assay (ELISA) and reverse-transcription polymerase chain reaction (RT-PCR). The SG rate was 78 ± 2.8-100 ± 0% in all treatments. A total of 1.5% of 1,604 seedlings infected singly showed symptoms, whereas in diagnostics testing, viruses were detected in 2.6% of plants, indicating occurrence of asymptomatic ST. The highest rate of transmission observed for single infections was 17% CMV in IT98K-133-1-1, 17.1% BCMV-BlCM in IT98K-503-1, and 2.3% SBMV in IT99K-1060. The highest CMV frequency under coinfection was 22.2% in plants inoculated (PI) with SBMV + CMV, 4.2% for BCMV-BlCM in PI with BCMV-BlCM + CMV and 2.3% for SBMV in PI with BCMV-BlCM + SBMV + CMV. This study indicated high variation in the rates of ST based on cultivar and virus type, and for each virus under mixed-infection conditions. Diagnostic confirmation detected a higher percentage of seed-transmitted viruses compared to visual assessment, warranting the need for diagnostics for the reliable detection of seed-transmitted viruses.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13337-024-00899-2.</p>","PeriodicalId":23708,"journal":{"name":"VirusDisease","volume":"35 4","pages":"609-619"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11635052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A sensitive batch detection of <i>banana bunchy top virus</i> using SYBR^® Green real-time PCR.","authors":"Jay-Vee S Mendoza, Fe M Dela Cueva, Jen Daine L Nocum, Anand Noel C Manohar, Roanne R Gardoce, Grace C Lachica, Darlon V Lantican","doi":"10.1007/s13337-024-00897-4","DOIUrl":"10.1007/s13337-024-00897-4","url":null,"abstract":"<p><p><i>Banana bunchy top virus</i> (BBTV) is the most destructive viral disease of banana crop in the Philippines. The disease causes heavy damage to important local varieties, 'Lakatan' and 'Cavendish'. Infected planting materials can cause long-term disease transmission causing geographical location to dictate genetic variation among viral strains. Hence, there is a need for an efficient and reliable quarantine detection procedure. This study developed a high-throughput real-time PCR protocol for batch detection of BBTV. A primer set derived from the <i>DNA-R</i> region of the virus was designed for specific BBTV detection. Tests for optimal annealing temperature, sample load, and sensitivity were performed. Finally, the cost per sample was compared to conventional end-point PCR. Optimization of the annealing temperature, from 55.5 ℃ to 63.5 ℃, yielded virus detection. The detection protocol developed was efficient to detect BBTV from a leaf disc measuring up to 5 mm diameter and weight of approximately 3 mg. DNA from infected leaf discs was detectable up to 1:10000 dilution. Sample pooling was detectable up to 1:99 infected to healthy leaf disc ratio. This sensitive and cost-efficient batch detection method for BBTV detection will be useful for quarantine services and various diagnostic applications.</p>","PeriodicalId":23708,"journal":{"name":"VirusDisease","volume":"35 4","pages":"637-647"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11635069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring immunogenic CD8 + T-cell epitopes for peptide-based vaccine development against evolving SARS-CoV-2 variants: An immunoinformatics approach.","authors":"Mohd Sultan Khan, Madhvi Shakya, Chandan Kumar Verma","doi":"10.1007/s13337-024-00894-7","DOIUrl":"10.1007/s13337-024-00894-7","url":null,"abstract":"<p><p>The COVID-19 pandemic originated in Wuhan in 2019 due to a novel SARS-COV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) responsible for the massive number of deaths across the globe. So far, several vaccines have been developed using highly antigenic Spike protein and authorized for emergency use, reducing the severity of the infection. Nonetheless, the virus continues to evolve through multiple mutations, resulting in numerous variants with enhanced transmission that evade the vaccine-induced immune response. Given the persistently mutating nature of the SARS-COV-2 virus, peptide-based vaccines with highly conserved epitopes may offer lasting protection against evolving variants. This study presents an immunoinformatics-based identification of potentially immunogenic CD8 + T-cell epitopes (CTLs) of Spike (S), Membrane (M), Nucleocapsid (N) and Envelope (E) proteins of SARS-COV-2. By utilizing the immunoinformatic approach, 21 epitopes have successfully been evaluated, where 15, 3, 2, and 1 epitopes are respectively from Spike, Membrane, Envelope and Nucleocapsid proteins. Out of these, 20 are found to be identical with experimentally verified immunogenic epitopes, except for the novel NTQEVFAQV epitope from spike protein. These epitopes show a high degree of conservation in both former variants of concerns (VOCs), variants of interest (VOIs) and current variants under monitoring (VUMs), are non-toxic, non-homologous to humans and have a wide range of global population coverage. Furthermore, utilizing molecular docking analysis followed by molecular dynamics simulation, these epitopes have been verified as having stable interactions with their respective HLA molecules. The described framework and projected immunogenic epitopes could significantly impact the development of SARS-COV-2 vaccines based on peptides.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13337-024-00894-7.</p>","PeriodicalId":23708,"journal":{"name":"VirusDisease","volume":"35 4","pages":"553-566"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11635080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of SARS-CoV-2 RNA detection in different types of clinical specimens among suspected COVID-19 patients in Addis Ababa, Ethiopia.","authors":"Tadesse Lejisa, Rozina Ambachew, Demiraw Bikila, Chala Bashea, Abera Abdeta, Dawit Chala, Natnael Dejene, Habteyes Hailu Tola, Gadissa Bedada Hundie","doi":"10.1007/s13337-024-00892-9","DOIUrl":"10.1007/s13337-024-00892-9","url":null,"abstract":"<p><p>Although nasopharyngeal swabs (NPSs) are superior to saliva specimens, saliva can be used as an alternative specimen for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. Moreover, studies have reported contradicting findings on whether SARS-CoV-2 can be detected in urine or not. Thus, we aimed to evaluate the diagnostic utility of NPSs, saliva and urine specimens in suspected COVID-19 patients. We conducted a cross-sectional study among a total of 604 specimens collected from 219 individuals suspected for COVID-19 from February to July 2022. We recruited participants from two COVID-19 isolation and treatment centers in Addis Ababa. We analyzed the specimens by real-time reverse transcriptase polymerase chain reaction (RT-PCR) with a Cobas 8800 automated system. The presence of SARS-CoV-2 in NPS, saliva, and urine samples was measured by cycle threshold (Ct) values. Descriptive statistics such as frequency, percent, and mean with standard deviation were used to summarize participants characteristics. We conducted chi-square test to compare RT‒PCR results of NPS, saliva and urine specimens. All data was analyzed by SPSS version 27, and the level of significance was set at a <i>p</i> value ≤ 0.05. Of the 219 participants, 126 (57.5%) were positive for SARS-CoV-2 either from NPS, saliva, urine or all specimens. The rate of SARS-CoV-2 detection was significantly higher in NPS (53.9%) than in saliva (35.2%; <i>p</i> = 0.001) and urine (9.0%; <i>p</i> = 0.001) specimens. The percentage of positive agreement between NPS and saliva was 92.2%, while negative agreement was 66.9%. The overall agreement between NPS and saliva was 75.8% (K = 0.53, <i>p</i> < 0.001). In addition, there was a significant correlation in Ct values of both ORF1ab and E genes between the paired NPS and saliva specimens. There was significant positive correlation between NPS and saliva specimens Ct values of both ORF1ab and E genes and days from onset of symptoms to specimen collection. SARS-CoV-2 was significantly detected in NPS than in saliva and urine specimens. Although NPS is better for SARS-CoV-2 detection, saliva specimen can be used as an alternative clinical specimen in resource-limited settings where access to swabs is limited. Both saliva and urine could be sources of viral transmission.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13337-024-00892-9.</p>","PeriodicalId":23708,"journal":{"name":"VirusDisease","volume":"35 4","pages":"567-576"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11635055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Burden of rotavirus and adenovirus gastroenteritis in children and adults hospitalized in two geo-climatically different provinces of Sri Lanka.","authors":"N P Sunil-Chandra, M V M L Jayasundara, B C G Mendis, D M P V Dissanayaka","doi":"10.1007/s13337-024-00893-8","DOIUrl":"10.1007/s13337-024-00893-8","url":null,"abstract":"<p><p>Acute gastroenteritis is common in infants and children of Sri Lanka. There is limited information on the burden of rotavirus gastroenteritis in infants and children in Sri Lanka but none in adults. Adenovirus gastroenteritis is not previously reported in Sri Lanka. This study is aimed to determine the viral etiology of acute gastroenteritis in hospitalized infants, children and adults of two geo-climatically different provinces of Sri Lanka. Diarrhoeic specimens from patients hospitalized with acute gastroenteritis in Western (n = 300) and Central (n = 271) provinces of Sri Lanka were tested for rotavirus and enteric adenovirus antigens by Enzyme Linked Immunosorbent Assay. In Western and Central provinces, overall positivity was 25.3 and 44.7% for rotavirus, 1.7 and 3.3% for enteric adenoviruses and, 0.7 and 1.5% for co-infections with rotavirus and adenovirus respectively. In children of Western and Central provinces, the positivity was 32.1 and 52.9% for rotavirus, and 2.2 and 3.4% for enteric adenoviruses respectively, whereas among adults, the positivity was 13.9 and 15.6% for rotavirus, and 0.9 and 0% for enteric adenoviruses respectively. Occurrence of rotavirus gastroenteritis in hospitalized children is significantly higher compared to adults in both Western and Central provinces. Adenovirus gastroenteritis in Sri Lanka occurs at a very low frequency with no significant difference between children and adults in both provinces. Rotavirus and adenovirus co-infection also occurs at a very low frequency.</p>","PeriodicalId":23708,"journal":{"name":"VirusDisease","volume":"35 4","pages":"620-629"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11635066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New thiourea derivatives that target the episomal silencing SMC5 protein to inhibit HBx-dependent viral DNA replication and gene transcription.","authors":"Jitendra Kumar, Ankita Singh, Purnima Tyagi, Deepti Sharma, Shiv Kumar Sarin, Vijay Kumar","doi":"10.1007/s13337-024-00895-6","DOIUrl":"10.1007/s13337-024-00895-6","url":null,"abstract":"<p><p>Antivirals such as nucleotide analogs (NAs) are potent inhibitors of hepatitis B virus (HBV) replication. However, NAs fail to diminish the signaling and mitogenic activities of the transactivator HBx protein. Earlier we have shown that thiourea derivative IR-415 (DSA-00) targeted HBx to down-regulate its target viral and host genes. However, the molecular mechanism of its antiviral action is poorly understood. Here we investigated the anti-HBV properties of DSA-00 and its new derivatives in cell culture models. DSA-00 and its derivatives DSA-02 and DSA-09 not only suppressed HBV DNA levels similar to well-known antiviral Entecavir but also diminished the expression of pgRNA and secretion of HBsAg and HBeAg. Apparently, the three DSA derivatives inhibited the viral pregenomic RNA expression by stabilizing the episomal DNA silencing protein SMC5, suppressed transcription from viral and host gene promoters, and normalized intracellular CDK2 activity. As none the compounds are reportedly cytotoxic, thiourea derivatives could be good candidates for developing future antivirals for a functional cure of hepatitis B infection.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13337-024-00895-6.</p>","PeriodicalId":23708,"journal":{"name":"VirusDisease","volume":"35 4","pages":"577-588"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11635082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}