Virus research最新文献

{"title":"Diphyllin elicits a doubled-pronged attack on the entry of SARS-CoV-2 by inhibiting cathepsin L and furin","authors":"Binli Mao ,&nbsp;Vu Thuy Khanh Le-Trilling ,&nbsp;Haihuan Tang ,&nbsp;Jie Hu ,&nbsp;Mona S. Schmitz ,&nbsp;Kimberly Barbet ,&nbsp;Dan Xu ,&nbsp;Zhen Wei ,&nbsp;Beinu Guo ,&nbsp;Denise Mennerich ,&nbsp;Chun Yao ,&nbsp;Jinxin Liu ,&nbsp;Zhenghan Li ,&nbsp;Yushun Wan ,&nbsp;Xiaoyong Zhang ,&nbsp;Kai Wang ,&nbsp;Ni Tang ,&nbsp;Zebo Yu ,&nbsp;Mirko Trilling ,&nbsp;Yong Lin","doi":"10.1016/j.virusres.2024.199485","DOIUrl":"10.1016/j.virusres.2024.199485","url":null,"abstract":"<div><div>The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) pandemic, posing serious threats to global health. Effective broad-spectrum antiviral drugs for the treatment of COVID-19 are not sufficiently available. In the present study, we investigated the antiviral activity of the natural lignan diphyllin (PubChem CID 100492) against different SARS-CoV-2 variants and explored the underlying molecular mechanisms. We found that diphyllin dose-dependently inhibits the SARS-CoV-2 spike (<em>S</em>)-mediated entry into different types of cells. The potent inhibition was evident against spike proteins derived from the original SARS-CoV-2 and from variants of concern such as Alpha, Beta, Delta or Omicron<em>.</em> Accordingly, diphyllin also significantly inhibited the <em>in vitro</em> infection of a clinical SARS-CoV-2 virus isolate. Mechanistically, diphyllin simultaneously inhibited the endosomal entry of SARS-CoV-2 by neutralizing the endosomal acidification and reducing the activity of the cysteine protease cathepsin L (CTSL) as well as S-meditated cell surface entry by impairing furin activity. Collectively, our findings establish diphyllin as novel inhibitor of CTSL and furin proteases, resulting in a double-pronged attack on SARS-CoV-2 entry along endosomal as well as cell surface routes. Therefore, diphyllin has the potential to be advanced as an inhibitor of SARS-CoV-2 entry.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"350 ","pages":"Article 199485"},"PeriodicalIF":2.5,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biology of human respiratory syncytial virus: Current perspectives in immune response and mechanisms against the virus","authors":"Abayeneh Girma","doi":"10.1016/j.virusres.2024.199483","DOIUrl":"10.1016/j.virusres.2024.199483","url":null,"abstract":"<div><div>Human respiratory syncytial virus (hRSV) remains a leading cause of morbidity and mortality in infants, young children, and older adults. hRSV infection's limited treatment and vaccine options significantly increase bronchiolitis' morbidity rates. The severity and outcome of viral infection hinge on the innate immune response. Developing vaccines and identifying therapeutic interventions suitable for young children, older adults, and pregnant women relies on comprehending the molecular mechanisms of viral PAMP recognition, genetic factors of the inflammatory response, and antiviral defense. This review covers fundamental elements of hRSV biology, diagnosis, pathogenesis, and the immune response, highlighting prospective options for vaccine development.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"350 ","pages":"Article 199483"},"PeriodicalIF":2.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic features of avian influenza (A/H5N8) clade 2.3.4.4b isolated from quail in Egypt","authors":"Mohamed H. Elhusseiny ,&nbsp;Moataz M. Elsayed ,&nbsp;Wesam H. Mady ,&nbsp;Osama Mahana ,&nbsp;Neveen R. Bakry ,&nbsp;Ola Abdelaziz ,&nbsp;Abdel-Sattar Arafa ,&nbsp;Momtaz A. Shahein ,&nbsp;Samah Eid ,&nbsp;Mahmoud M. Naguib","doi":"10.1016/j.virusres.2024.199482","DOIUrl":"10.1016/j.virusres.2024.199482","url":null,"abstract":"<div><div>Several genotypes of the highly pathogenic avian influenza (HPAI) virus H5N8 subtype within clade 2.3.4.4b continue to circulate in different species of domestic birds across Egypt. It is believed that quail contribute to virus replication and adaptation to other gallinaceous poultry species and humans. This study provides genetic characterization of the full genome of HPAI H5N8 isolated from quail in Egypt. The virus was isolated from a commercial quail farm associated with respiratory signs. To characterize the genetic features of the detected virus, gene sequencing via Sanger technology and phylogenetic analysis were performed. The results revealed high nucleotide identity with the HPAI H5N8 virus from Egypt, which has multiple basic amino acid motifs PLREKRRKR/GLF at the hemagglutinin (HA) cleavage site. Phylogenetic analysis of the eight gene segments revealed that the quail isolate is grouped with HPAI H5N8 viruses of clade 2.3.4.4b and closely related to the most recent circulating H5N8 viruses in Egypt. Whole-genome characterization revealed amino acid preferences for avian receptors with few mutations, indicating their affinity for human-like receptors and increased virulence in mammals, such as S123P, S133A, T156A and A263T in the HA gene. In addition, the sequencing results revealed a lack of markers associated with influenza antiviral resistance in the neuraminidase and matrix-2 coding proteins. The results of the present study support the spread of HPAIV H5N8 to species other than chickens in Egypt. Therefore, continuous surveillance of AIV in different bird species in Egypt followed by full genomic characterization is needed for better virus control and prevention.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"350 ","pages":"Article 199482"},"PeriodicalIF":2.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The zoonotic LCK-3110 strain of Rocahepevirus ratti leads to mild infection in chickens after experimental inoculation","authors":"Kush Kumar Yadav ,&nbsp;Patricia A Boley ,&nbsp;Saroj Khatiwada ,&nbsp;Carolyn M Lee ,&nbsp;Menuka Bhandari ,&nbsp;Ronna Wood ,&nbsp;Juliette Hanson ,&nbsp;Scott P. Kenney","doi":"10.1016/j.virusres.2024.199477","DOIUrl":"10.1016/j.virusres.2024.199477","url":null,"abstract":"<div><div><em>Rocahepevirus ratti</em> [rat hepatitis E virus (HEV)] was originally isolated from rats and found to be non-infectious to nonhuman primates, suggesting humans were not a susceptible host. However, in 2018, rat HEV infections were identified in human patients. High seroprevalence for rat HEV in rats in many countries necessitates studying this emerging zoonotic outbreak. Lack of a human derived rat HEV infectious clone, cell culture systems, and animal models have hindered this effort. In response to the increase in human infection cases by rat HEV, we utilized an infectious clone of the zoonotic rat HEV LCK-3110 strain originally reported from human cases. Capped RNA transcripts of the rat HEV LCK-3110 strain were synthesized, and replication was assessed in both cell culture via transfection and chickens via intrahepatic inoculation. Naive chickens were cohoused together with inoculated chickens. Our results demonstrated that although chickens were susceptible, virus replication was inefficient with only a few of the chickens inoculated with rat HEV having low levels of viremia and fecal virus shedding. However, LCK-3110 HEV was able to transmit between chickens as several naive cohoused chickens became infected as evidenced by viremia, fecal shedding, and the presence of viral protein upon histopathology of the liver. Rat HEV is an emerging zoonotic virus with an ability to spillover across species. Chickens have potential to serve as intermediary hosts, possibly playing a role in rat HEV spread and exposure to humans.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"350 ","pages":"Article 199477"},"PeriodicalIF":2.5,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human pegivirus -1 (HPgV-1) RNA frequency and genotype distribution in pediatric oncology patients with febrile neutropenia","authors":"Anielly Sarana da Silva ,&nbsp;Gabriel Montenegro de Campos ,&nbsp;Gabriela Marengone Altizani ,&nbsp;Alice Chagas Barros ,&nbsp;Dennis Maletich Junqueira ,&nbsp;Simone Kashima ,&nbsp;Sandra Coccuzzo Sampaio ,&nbsp;Maria Carolina Elias ,&nbsp;Marta Giovanetti ,&nbsp;Carlos Alberto Scrideli ,&nbsp;Svetoslav Nanev Slavov","doi":"10.1016/j.virusres.2024.199479","DOIUrl":"10.1016/j.virusres.2024.199479","url":null,"abstract":"<div><div>Human Pegivirus-1, typically regarded as a commensal virus, exhibits high prevalence in humans. Its frequency and impact on oncologic pediatric patients with febrile neutropenia (FN), a frequent chemotherapy complication, remains unexplored. In this study, we assessed HPgV-1 RNA prevalence in pediatric patients experiencing FN. Blood samples were collected from 30 children, 15 presenting FN and 15 comprising a control group of either undergoing treatment or in remission. Overall, HPgV-1 RNA was detected in 23.3 % of samples (26.7 % among FN patients and 20.0 % among those under treatment or in remission). Phylogenetic analysis unveiled HPgV-1 genotype 2 predominance among these samples, the most prevalent strain circulating in Brazil. Our findings prompt crucial inquiries into the role of HPgV-1 RNA in FN: is it an incidental finding and if it can influences this clinical entity? Further investigation is imperative to elucidate HPgV-1 implications in vulnerable patients cohorts, potentially informing new approaches and understanding viral dynamics in immunocompromised populations.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"350 ","pages":"Article 199479"},"PeriodicalIF":2.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Verteporfin is an effective inhibitor of HCMV replication","authors":"Woo Young Lim ,&nbsp;Ju Hyun Lee ,&nbsp;Youngju Choi ,&nbsp;Keejung Yoon","doi":"10.1016/j.virusres.2024.199475","DOIUrl":"10.1016/j.virusres.2024.199475","url":null,"abstract":"<div><div>Human cytomegalovirus (HCMV), a double-stranded DNA virus from the <em>Betaherpesvirinae</em> subfamily, constitutes significant risks to newborns and immunocompromised individuals, potentially leading to severe neurodevelopmental disorders. The purpose of this study was to identify FDA-approved drugs that can inhibit HCMV replication through a drug repositioning approach. Using an HCMV progeny assay, verteporfin, a medication used as a photosensitizer in photodynamic therapy, was found to inhibit HCMV production in a dose-dependent manner, significantly reducing replication at concentrations as low as 0.5 µM, approximately 1/20th of the concentration used in anti-cancer research. Further analysis revealed that verteporfin did not interfere with HCMV host cell entry or nuclear transport but reduced viral mRNA and protein levels throughout the HCMV life cycle from the immediate-early stages. These results suggest that verteporfin has the potential to be rapidly and safely developed as a repurposed drug to inhibit HCMV infection.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"350 ","pages":"Article 199475"},"PeriodicalIF":2.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Viral coexistence and insertional mutations in the ORF8 region of SARS-CoV-2: A possible mechanism of nucleotide insertion","authors":"Miuko Kurose ,&nbsp;Akima Yamamoto ,&nbsp;Abeer Mohamed Abdelfattah Elsayed ,&nbsp;Basirat Mojisola Lawal-Ayinde ,&nbsp;Toshihito Nomura ,&nbsp;Akifumi Higashiura ,&nbsp;Takashi Irie ,&nbsp;Masaya Fukushi ,&nbsp;Miyuki Kanda ,&nbsp;Hidetoshi Tahara ,&nbsp;Daichi Morita ,&nbsp;Teruo Kuroda ,&nbsp;Ko Ko ,&nbsp;Kazuaki Takahashi ,&nbsp;Junko Tanaka ,&nbsp;Takemasa Sakaguchi","doi":"10.1016/j.virusres.2024.199478","DOIUrl":"10.1016/j.virusres.2024.199478","url":null,"abstract":"<div><div>The virus obtained from a swab sample ID: S66 in Hiroshima was reported to have a single T-base insertion in the ORF8 coding region. However, no T insertion was observed when we determined the genomic sequence using another method. We then extracted RNA from the S66 swab sample and sequenced the insertion site using the Sanger method. The resulting waveform was disrupted beyond the insertion site, suggesting the presence of a mixed population of viruses with different sequences. Through plasmid cloning of RT-PCR amplification fragments and virus cloning by limiting dilution, along with TIDE analysis to determine the ratio of components from the Sanger sequencing waveform, it was confirmed that the sample contained a mixture of viruses with varying numbers of T-base insertions. The virus with one T insertion (T1+) was predominant in 70–75 % of the genomes, and genomes with T0, T2+, T3+, T4+, and T5+ were also detected. No T-base insertion mutations were observed in the ORF8 region in three other SARS-CoV-2 samples. In the S66 sample, a C27911T point mutation near the insertion site in the ORF8 region resulted in a sequence of seven or more consecutive T bases, which was the cause of the T-base insertion. When the cloned S66 virus (T1+) was passaged in cultured cells, there was a tendency for viruses with more insertion bases to become dominant with successive generations, suggesting that the T-base insertion was due to polymerase stuttering. The insertion of T bases resulted in synthesis of deletion mutants of the ORF8 protein, but no significant change was observed in the proliferation of the viruses in cultured cells. A search of the GenBank database using NCBI BLAST for viruses similar to S66 with T-base insertion mutations revealed hundreds of viruses widely distributed on the molecular phylogenetic tree. These base insertion viruses were thought to have occasionally arisen during the virus infection process. This study suggests one mechanism of insertion mutations in SARS-CoV-2, and it is important to consider the emergence of future mutant strains.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"350 ","pages":"Article 199478"},"PeriodicalIF":2.5,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the emergence of highly pathogenic avian influenza A virus H5N1 in pinnipeds: An evolutionary approach","authors":"Mercedes Paz ,&nbsp;Valentina Franco-Trecu ,&nbsp;Diana Szteren ,&nbsp;Alicia Costábile ,&nbsp;Cecilia Portela ,&nbsp;Alfredo Bruno ,&nbsp;Gonzalo Moratorio ,&nbsp;Pilar Moreno ,&nbsp;Juan Cristina","doi":"10.1016/j.virusres.2024.199472","DOIUrl":"10.1016/j.virusres.2024.199472","url":null,"abstract":"<div><div>Highly pathogenic influenza A virus (HPIAV) H5N1 within the genetic clade 2.3.4.4b has emerged in wild birds in different regions of the world, leading to the death of &gt;70 million birds. When these strains spread to pinniped species a remarkable mortality has also been observed. A detailed genetic characterization of HPIAV isolated from pinnipeds is essential to understand the potential spread of these viruses to other mammalian species, including humans. To gain insight into these matters a detailed phylogenetic analysis of HPIAV H5N1 2.3.4.4b strains isolated from pinniped species was performed. The results of these studies revealed multiple transmission events from birds to pinnipeds in all world regions. Different evolutionary histories of different genes of HPIAV H5N1 2.3.4.4b strains gave rise to the viruses infecting pinnipeds in different regions of the world. European strains isolated from pinnipeds represent a completely different genetic lineage from strains isolated from South American ones. All strains isolated from pinnipeds bear characteristics of a highly pathogenic form for of avian influenza in poultry. Amino acid substitutions, previously shown to confer an adaptive advantage for infecting mammals, were observed in different genes in all pinniped species studied.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"350 ","pages":"Article 199472"},"PeriodicalIF":2.5,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dothistroma septosporum and Dothistroma pini, the causal agents of Dothistroma needle blight, are infected by multiple viruses","authors":"Miloš Trifković ,&nbsp;Ondřej Hejna ,&nbsp;Anna Kuznetsova ,&nbsp;Martin Mullett ,&nbsp;Libor Jankovský ,&nbsp;Leticia Botella","doi":"10.1016/j.virusres.2024.199476","DOIUrl":"10.1016/j.virusres.2024.199476","url":null,"abstract":"<div><div><em>Dothistroma septosporum</em> and <em>Dothistroma pini</em> are severe foliar pathogens of conifers. They infect a broad spectrum of hosts (mainly <em>Pinus</em> spp.), causing chlorosis, defoliation of needles, and eventually the death of pine trees in extreme cases. Mycoviruses represent a novel and innovative avenue for controlling pathogens. To search for possible viruses hosted by <em>Dothistroma</em> spp<em>.</em> we screened a subset of isolates (20 strains of <em>D. septosporum</em> and one <em>D. pini</em>) originating from the Czech Republic, Slovenia, Italy, Austria and Ireland for viral dsRNA segments. Only five of them showed the presence of dsRNA segments. A total of 21 fungal isolates were prepared for total RNA extractions. RNA samples were pooled, and two separate RNA libraries were constructed for stranded total RNA sequencing. RNA-Seq data processing, pairwise sequence comparisons (PASC) and phylogenetic analyses revealed the presence of thirteen novel putative viruses with varying genome types: seven negative-sense single-stranded RNA viruses, including six bunya-like viruses and one new member of the order <em>Mononegavirales</em>; three positive-sense single-stranded RNA viruses, two of which are similar to those of the family <em>Narnaviridae</em>, while the genome of the third correspond to those of the family <em>Gammaflexiviridae;</em> and three double-stranded RNA viruses, comprising two novel members of the family <em>Chrysoviridae</em> and a potentially new species of gammapartitivirus. The results were confirmed with RT-PCR screening that the fungal pathogens hosted all the viruses and showed that particular fungal strains harbour multiple virus infections and that they are transmitted vertically. In this study, we described the narnavirus infecting <em>D. pini</em>. To our knowledge, this is the first virus discovered in <em>D. pini</em>.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"350 ","pages":"Article 199476"},"PeriodicalIF":2.5,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolation and characterization of lytic bacteriophage vB_KpnP_23: A promising antimicrobial candidate against carbapenem-resistant Klebsiella pneumoniae","authors":"Qian Wang ,&nbsp;Ran Chen ,&nbsp;Hui Liu ,&nbsp;Yue Liu ,&nbsp;Jinmei Li ,&nbsp;Yueling Wang ,&nbsp;Yan Jin ,&nbsp;Yuanyuan Bai ,&nbsp;Zhen Song ,&nbsp;Xinglun Lu ,&nbsp;Changyin Wang ,&nbsp;Yingying Hao","doi":"10.1016/j.virusres.2024.199473","DOIUrl":"10.1016/j.virusres.2024.199473","url":null,"abstract":"<div><div>The global health threat posed by carbapenem-resistant <em>Klebsiella pneumoniae</em> (CRKP) is exacerbated by the limited availability of effective treatments. Bacteriophages are promising alternatives to conventional antimicrobial agents. However, current phage databases are limited. Thus, identifying and characterizing new phages could provide biological options for the treatment of multi-drug resistant bacterial infections. Here, we report the characterization of a novel lytic phage, vB_KpnP_23, isolated from hospital sewage. This phage exhibited potent activity against carbapenemase-producing CRKP strains and was characterised by an icosahedral head, a retractable tail, and a genome comprising 40,987 base pairs, with a G + C content of 51 %. Capable of targeting and lysing nine different capsule types (K-types) of CRKP, including the clinically relevant ST11-K64, it demonstrated both high bacteriolytic efficiency and stability in various environmental contexts. Crucially, vB_KpnP_23 lacks virulence factors, antimicrobial resistance genes, or tRNA, aligning with the key criteria for therapeutic application. In vitro evaluation of phage-antibiotic combinations revealed a significant synergistic effect between vB_KpnP_23 and meropenem, levofloxacin, or amikacin. This synergy could lead to an 8-fold reduction in the minimum inhibitory concentration (MIC), suggesting that integrated treatments combining this phage with the aforementioned antibiotics may substantially enhance drug effectiveness. This approach not only extends the clinical utility of these antibiotics but also presents a strategic advance in combating antibiotic resistance. Specifically, it underscores the potential of phage-antibiotic combinations as a powerful tool in the treatment of infections caused by CRKP, offering a promising avenue to mitigate the public health challenges of antibiotic-resistant pathogens.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"350 ","pages":"Article 199473"},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}