Pub Date : 2024-12-01Epub Date: 2024-11-29DOI: 10.1007/s13337-024-00900-y
Vimal K Maurya, Swatantra Kumar, Shivani Maurya, Saniya Ansari, Janusz T Paweska, Ahmed S Abdel-Moneim, Shailendra K Saxena
Monkeypox virus (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.
Graphical abstract: 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.
{"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}
Pub Date : 2024-12-01Epub Date: 2024-11-19DOI: 10.1007/s13337-024-00899-2
K E Ogunsola, P Lava Kumar
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.
Supplementary information: The online version contains supplementary material available at 10.1007/s13337-024-00899-2.
{"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}
Pub Date : 2024-12-01Epub Date: 2024-11-13DOI: 10.1007/s13337-024-00897-4
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
Banana bunchy top virus (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 DNA-R 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.
{"title":"A sensitive batch detection of <i>banana bunchy top virus</i> using SYBR<sup>®</sup> 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}
Pub Date : 2024-12-01Epub Date: 2024-09-30DOI: 10.1007/s13337-024-00894-7
Mohd Sultan Khan, Madhvi Shakya, Chandan Kumar Verma
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.
Supplementary information: The online version contains supplementary material available at 10.1007/s13337-024-00894-7.
{"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}
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 p 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%; p = 0.001) and urine (9.0%; p = 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, p < 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.
Supplementary information: The online version contains supplementary material available at 10.1007/s13337-024-00892-9.
{"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}
Pub Date : 2024-12-01Epub Date: 2024-09-24DOI: 10.1007/s13337-024-00893-8
N P Sunil-Chandra, M V M L Jayasundara, B C G Mendis, D M P V Dissanayaka
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.
{"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}
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.
Supplementary information: The online version contains supplementary material available at 10.1007/s13337-024-00895-6.
{"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}
Pub Date : 2024-12-01Epub Date: 2024-10-19DOI: 10.1007/s13337-024-00898-3
B Sravani, V Kavi Sidharthan, Vijayprakash Reddy
Plant-infecting alphaflexiviruses cause moderate to severe diseases in economically important crops worldwide. In the present study, we identified nine putative novel alphaflexiviruses in nine plant species by exploring the publicly available plant transcriptome data in Sequence Read Archive (SRA) database. Coding-complete genomes of all the identified viruses were recovered and contained five to six open reading frames (ORFs). ORFs 1-5 encode replicase (Rep), triple gene block (TGB) proteins 1-3 and coat protein (CP), respectively. The additional ORF6, identified in two viruses, encoded the nucleic acid-binding (NB) protein or a protein with no significant similarity to known viral sequences. Genome organization of the first alphaflexivirus identified in a gymnospermic host (black pine potex-like virus 1-BlpPV1) slightly differed from that of known alphaflexiviruses and formed a distinct sub-clade in phylogenetic analysis. Thus, BlpPV1 can represent a novel taxon within the family Alphaflexiviridae. Based on phylogeny, sequence similarity to known members and sequence-based species demarcation criteria, six other identified viruses were tentatively assigned to the genera Potexvirus (4), Lolavirus (1) and Mandarivirus (1), while the two lola-like viruses may potentially represent a new genus. Further studies are needed to understand the biology and geographical spread of identified novel viruses.
Supplementary information: The online version contains supplementary material available at 10.1007/s13337-024-00898-3.
{"title":"Identification of nine putative novel members of plant-infecting alphaflexiviruses in public domain plant transcriptomes.","authors":"B Sravani, V Kavi Sidharthan, Vijayprakash Reddy","doi":"10.1007/s13337-024-00898-3","DOIUrl":"10.1007/s13337-024-00898-3","url":null,"abstract":"<p><p>Plant-infecting alphaflexiviruses cause moderate to severe diseases in economically important crops worldwide. In the present study, we identified nine putative novel alphaflexiviruses in nine plant species by exploring the publicly available plant transcriptome data in Sequence Read Archive (SRA) database. Coding-complete genomes of all the identified viruses were recovered and contained five to six open reading frames (ORFs). ORFs 1-5 encode replicase (Rep), triple gene block (TGB) proteins 1-3 and coat protein (CP), respectively. The additional ORF6, identified in two viruses, encoded the nucleic acid-binding (NB) protein or a protein with no significant similarity to known viral sequences. Genome organization of the first alphaflexivirus identified in a gymnospermic host (black pine potex-like virus 1-BlpPV1) slightly differed from that of known alphaflexiviruses and formed a distinct sub-clade in phylogenetic analysis. Thus, BlpPV1 can represent a novel taxon within the family <i>Alphaflexiviridae</i>. Based on phylogeny, sequence similarity to known members and sequence-based species demarcation criteria, six other identified viruses were tentatively assigned to the genera <i>Potexvirus</i> (4), <i>Lolavirus</i> (1) and <i>Mandarivirus</i> (1), while the two lola-like viruses may potentially represent a new genus. Further studies are needed to understand the biology and geographical spread of identified novel viruses.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13337-024-00898-3.</p>","PeriodicalId":23708,"journal":{"name":"VirusDisease","volume":"35 4","pages":"630-636"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11635070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830069","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}
Pub Date : 2024-09-01Epub Date: 2024-10-03DOI: 10.1007/s13337-024-00896-5
Abhishek Padhi, Ashwini Agarwal, Praggya Mishra, Ekta Gupta, Swatantra Kumar, C D S Katoch, Shailendra K Saxena
Chandipura vesiculovirus (CHPV) is an emerging neurotropic virus primarily affecting children and causing acute encephalitis syndrome (AES) in India. The virus, transmitted mainly by sand flies, has led to multiple outbreaks with high mortality rates, particularly in rural and resource-limited settings. CHPV infection is characterized by rapid disease progression, with symptoms ranging from fever and seizures to coma and death, often within 24 to 48 h of onset. The current management of CHPV is limited to supportive care due to the lack of specific antiviral therapies. Diagnosis relies on laboratory methods such as RT-PCR, serology, and immunofluorescence, though these face challenges due to the rapid progression of the disease and the need for timely sample collection and analysis. Prevention strategies are focused on vector control through insecticide use and public health interventions, including community education and early detection programs. Despite some progress in understanding CHPV, significant research gaps remain, particularly in developing effective antiviral treatments and vaccines, understanding transmission dynamics, and improving diagnostic capabilities. The potential for the virus to spread globally due to factors like climate change and increased human movement underscores the need for international collaboration in surveillance and response efforts. Strengthening public health infrastructure, enhancing vector control measures, and fostering global partnerships are crucial steps toward mitigating the impact of CHPV and preventing future outbreaks. Continued research and proactive public health strategies are essential to protect vulnerable populations and control the spread of this potentially deadly virus.
{"title":"Re-emerging <i>Chandipura</i> <i>vesiculovirus</i>: A cause of concern for global health.","authors":"Abhishek Padhi, Ashwini Agarwal, Praggya Mishra, Ekta Gupta, Swatantra Kumar, C D S Katoch, Shailendra K Saxena","doi":"10.1007/s13337-024-00896-5","DOIUrl":"10.1007/s13337-024-00896-5","url":null,"abstract":"<p><p><i>Chandipura vesiculovirus</i> (CHPV) is an emerging neurotropic virus primarily affecting children and causing acute encephalitis syndrome (AES) in India. The virus, transmitted mainly by sand flies, has led to multiple outbreaks with high mortality rates, particularly in rural and resource-limited settings. CHPV infection is characterized by rapid disease progression, with symptoms ranging from fever and seizures to coma and death, often within 24 to 48 h of onset. The current management of CHPV is limited to supportive care due to the lack of specific antiviral therapies. Diagnosis relies on laboratory methods such as RT-PCR, serology, and immunofluorescence, though these face challenges due to the rapid progression of the disease and the need for timely sample collection and analysis. Prevention strategies are focused on vector control through insecticide use and public health interventions, including community education and early detection programs. Despite some progress in understanding CHPV, significant research gaps remain, particularly in developing effective antiviral treatments and vaccines, understanding transmission dynamics, and improving diagnostic capabilities. The potential for the virus to spread globally due to factors like climate change and increased human movement underscores the need for international collaboration in surveillance and response efforts. Strengthening public health infrastructure, enhancing vector control measures, and fostering global partnerships are crucial steps toward mitigating the impact of CHPV and preventing future outbreaks. Continued research and proactive public health strategies are essential to protect vulnerable populations and control the spread of this potentially deadly virus.</p>","PeriodicalId":23708,"journal":{"name":"VirusDisease","volume":"35 3","pages":"385-399"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509204","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}
Pub Date : 2024-09-01Epub Date: 2024-09-11DOI: 10.1007/s13337-024-00890-x
Varsha Ramesh, Kuralayanapalya P Suresh, Shijili Mambully, Swati Rani, Rakshit Ojha, Kirubakaran V Kumar, Vinayagamurthy Balamurugan
Peste des petits ruminants (PPR), an acute febrile viral disease impacting goats and sheep flocks, manifests with pyrexia, mucopurulent nasal and ocular discharges, necrotizing and erosive stomatitis, pneumonia, and enteritis. The disease-instigating agent, PPR virus, pertains to the Morbillivirus caprinae genus in the Paramyxoviridae family. The endemic presence of PPR in India results in notable economic losses due to heightened mortality and morbidity in infected animals. Understanding viral pathogen evolution is pivotal for delineating their emergence in diverse environments. This study explores the molecular evolutionary patterns of PPRV, concentrating on the N and F structural genes isolated from Indian sheep and goats. Analyzing evolutionary rate, phylogenetics, selection pressure, and codon usage bias, we determined the time to the most recent common ancestor (tMRCA) as 1984, 1973, 2000, and 2004 for goat and sheep's N and F genes, respectively, with evolutionary rates ranging from 2.859 x 103 to 4.995 x 104. The F-gene is found to exhibit a faster evolution than the N-gene, indicating apparent virus transmission across the regions of India, as supported by phylogenetic analysis. Codon usage bias examination, incorporating nucleotide composition and various plots (effective number of codon plot, parity plot, neutrality plot), suggests the evolution in India influenced by both natural selection and mutational pressure, resulting in alterations in the virus's codon bias. The integrated analysis underscores the significant role of selection pressures, implying PPRV's co-evolution and adaptations influenced by various genes. Insights from this study can guide effective disease control and vaccine development, aiding in managing PPR outbreaks in India and beyond.
小反刍兽疫(PPR)是一种影响山羊和绵羊群的急性发热性病毒病,表现为热病、粘液脓性鼻腔和眼分泌物、坏死性和侵蚀性口腔炎、肺炎和肠炎。致病原 PPR 病毒属于副粘病毒科帽状病毒属。由于受感染动物的死亡率和发病率上升,PPR 在印度的流行导致了显著的经济损失。了解病毒病原体的进化对于确定其在不同环境中的出现至关重要。本研究探讨了 PPRV 的分子进化模式,重点研究了从印度绵羊和山羊中分离出来的 N 和 F 结构基因。通过分析进化速度、系统发育、选择压力和密码子使用偏差,我们确定山羊和绵羊的 N 和 F 基因的最近共同祖先(tMRCA)时间分别为 1984 年、1973 年、2000 年和 2004 年,进化速度从 2.859 x 103 到 4.995 x 104 不等。F 基因的进化速度快于 N 基因,这表明病毒在印度各地区的传播速度明显加快,系统进化分析也证明了这一点。结合核苷酸组成和各种图谱(有效密码子数图谱、奇偶性图谱、中性图谱)对密码子使用偏向的研究表明,印度的进化受到自然选择和突变压力的影响,导致病毒的密码子偏向发生变化。综合分析强调了选择压力的重要作用,这意味着 PPRV 的共同进化和适应性受到各种基因的影响。这项研究的见解可以指导有效的疾病控制和疫苗开发,帮助管理印度及其他地区的 PPR 疫情。
{"title":"Dynamic evolution of peste des petits ruminants virus in sheep and goat hosts across India reveals the swift surge of F gene.","authors":"Varsha Ramesh, Kuralayanapalya P Suresh, Shijili Mambully, Swati Rani, Rakshit Ojha, Kirubakaran V Kumar, Vinayagamurthy Balamurugan","doi":"10.1007/s13337-024-00890-x","DOIUrl":"10.1007/s13337-024-00890-x","url":null,"abstract":"<p><p>Peste des petits ruminants (PPR), an acute febrile viral disease impacting goats and sheep flocks, manifests with pyrexia, mucopurulent nasal and ocular discharges, necrotizing and erosive stomatitis, pneumonia, and enteritis. The disease-instigating agent, PPR virus, pertains to the <i>Morbillivirus caprinae</i> genus in the <i>Paramyxoviridae</i> family. The endemic presence of PPR in India results in notable economic losses due to heightened mortality and morbidity in infected animals. Understanding viral pathogen evolution is pivotal for delineating their emergence in diverse environments. This study explores the molecular evolutionary patterns of PPRV, concentrating on the N and F structural genes isolated from Indian sheep and goats. Analyzing evolutionary rate, phylogenetics, selection pressure, and codon usage bias, we determined the time to the most recent common ancestor (tMRCA) as 1984, 1973, 2000, and 2004 for goat and sheep's N and F genes, respectively, with evolutionary rates ranging from 2.859 x 10<sup>3</sup> to 4.995 x 10<sup>4</sup>. The F-gene is found to exhibit a faster evolution than the N-gene, indicating apparent virus transmission across the regions of India, as supported by phylogenetic analysis. Codon usage bias examination, incorporating nucleotide composition and various plots (effective number of codon plot, parity plot, neutrality plot), suggests the evolution in India influenced by both natural selection and mutational pressure, resulting in alterations in the virus's codon bias. The integrated analysis underscores the significant role of selection pressures, implying PPRV's co-evolution and adaptations influenced by various genes. Insights from this study can guide effective disease control and vaccine development, aiding in managing PPR outbreaks in India and beyond.</p>","PeriodicalId":23708,"journal":{"name":"VirusDisease","volume":"35 3","pages":"505-519"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509199","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}