Oral USC-093, a novel homoserinamide analogue of the tyrosinamide (S)-HPMPA prodrug USC-087 has decreased nephrotoxicity while maintaining antiviral efficacy against human adenovirus infection of Syrian hamsters
Antiviral Res. 2024 Jan 6:105799. doi: 10.1016/j.antiviral.2024.105799. Online ahead of print.ABSTRACTAdenovirus infections of immunocompromised humans are a significant source of morbidity and mortality. Presently, there is no drug specifically approved for the treatment of adenovirus infections by the FDA. The state-of-the-art treatment of such infections is the off-label use of cidofovir, an acyclic nucleotide phosphonate. While cidofovir inhibits adenovirus replication, it has dose-limiting kidney toxicity. There is an apparent need for a better compound to treat adenovirus infections. To this end, we have been develop...
Source: Antiviral Research - January 8, 2024 Category: Virology Authors: Ann E Tollefson Samantha B Riemann Baoling Ying Jacqueline F Spencer Justin M Overhulse Boris A Kashemirov William S M Wold Charles E McKenna Karoly Toth Source Type: research
PZR suppresses innate immune response to RNA viral infection by inhibiting MAVS activation in interferon signaling mediated by RIG-I and MDA5
In conclusion, PZR and SHP2 suppress innate immune response to RNA viral infection through inhibiting MAVS activation. This study reveals the regulatory mechanism of PZR-SHP2-MAVS signal axis on IFN signaling mediated by RIG-I and MDA5, which may provide new sight for developing antiviral drugs.PMID:38185222 | DOI:10.1016/j.antiviral.2024.105797 (Source: Antiviral Research)
Source: Antiviral Research - January 7, 2024 Category: Virology Authors: Rilin Deng Lini Zhang Shengwen Chen Xinran Li Binbin Xue Huiyi Li Yan Xu Renyun Tian Qian Liu Luoling Wang Shun Liu Di Yang Penghui Li Songqing Tanga Haizhen Zhu Source Type: research
PZR suppresses innate immune response to RNA viral infection by inhibiting MAVS activation in interferon signaling mediated by RIG-I and MDA5
In conclusion, PZR and SHP2 suppress innate immune response to RNA viral infection through inhibiting MAVS activation. This study reveals the regulatory mechanism of PZR-SHP2-MAVS signal axis on IFN signaling mediated by RIG-I and MDA5, which may provide new sight for developing antiviral drugs.PMID:38185222 | DOI:10.1016/j.antiviral.2024.105797 (Source: Antiviral Research)
Source: Antiviral Research - January 7, 2024 Category: Virology Authors: Rilin Deng Lini Zhang Shengwen Chen Xinran Li Binbin Xue Huiyi Li Yan Xu Renyun Tian Qian Liu Luoling Wang Shun Liu Di Yang Penghui Li Songqing Tanga Haizhen Zhu Source Type: research
Genetically modified pigs lacking CD163 PSTII-domain-coding exon 13 are completely resistant to PRRSV infection
In this study, to determine whether the deletion of exon 13 is sufficient to confer resistance of pigs to PRRSV infection, we produced pigs possessing a defined CD163 exon 13 deletion (ΔExon13 pigs) and evaluated their susceptibility to viral infection. Wild type (WT) and CD163 modified pigs, placed in the same room, were infected with PRRSV-2. The modified pigs remained PCR and serologically negative for PRRSV throughout the study; whereas the WT pigs supported PRRSV infection and showed PRRSV related pathology. Importantly, our data also suggested that removal of exon 13 did not affect the main physiological function as...
Source: Antiviral Research - January 6, 2024 Category: Virology Authors: Brianna Salgado Rafael Bautista Rivas Derek Pinto Tad S Sonstegard Daniel F Carlson Kyra Martins Jonathan R Bostrom Yamlak Sinebo Raymond R R Rowland Alberto Brandariz-Nu ñez Source Type: research
Genetically modified pigs lacking CD163 PSTII-domain-coding exon 13 are completely resistant to PRRSV infection
In this study, to determine whether the deletion of exon 13 is sufficient to confer resistance of pigs to PRRSV infection, we produced pigs possessing a defined CD163 exon 13 deletion (ΔExon13 pigs) and evaluated their susceptibility to viral infection. Wild type (WT) and CD163 modified pigs, placed in the same room, were infected with PRRSV-2. The modified pigs remained PCR and serologically negative for PRRSV throughout the study; whereas the WT pigs supported PRRSV infection and showed PRRSV related pathology. Importantly, our data also suggested that removal of exon 13 did not affect the main physiological function as...
Source: Antiviral Research - January 6, 2024 Category: Virology Authors: Brianna Salgado Rafael Bautista Rivas Derek Pinto Tad S Sonstegard Daniel F Carlson Kyra Martins Jonathan R Bostrom Yamlak Sinebo Raymond R R Rowland Alberto Brandariz-Nu ñez Source Type: research
The absence of seroconversion after exposition to hepatitis C virus is not related to KIR-HLA genotype combinations (GEHEP-012 study)
CONCLUSIONS: Our results suggest that those KIR-HLA genotype combinations are not relevant factors involved in the lack of infection and seroconversion after exposition to HCV. More studies will be needed to completely understand this phenotype.PMID:38181855 | DOI:10.1016/j.antiviral.2024.105795 (Source: Antiviral Research)
Source: Antiviral Research - January 5, 2024 Category: Virology Authors: Carmen Mart ín-Sierra Mar ía José Bravo Mar ía Eugenia Sáez Itziar De Rojas Marta Santos Jesica Mart ín-Carmona Ana ïs Corma-Gómez Alejandro Gonz ález-Serna Jos é Luis Royo Juan A Pineda Antonio Rivero Antonio Rivero-Ju árez Juan Mac ías Luis Source Type: research
Chromatin binding protein HMGN1 promotes HBV cccDNA transcription and replication by regulating the phosphorylation of histone 3
CONCLUSIONS: In summary, our study identified that a host protein can bind to cccDNA and promote its transcription, providing a candidate strategy for anti-HBV targeting to interfere with the transcriptional activity of cccDNA microchromosomes.PMID:38181856 | DOI:10.1016/j.antiviral.2024.105796 (Source: Antiviral Research)
Source: Antiviral Research - January 5, 2024 Category: Virology Authors: Tan Ming Liu Yuting Dong Meiling Cheng Shengtao Ren Jihua Zhang Hui Chen Wanjin Li Dian Gao Tingting Chen Juan Zhang Zhenzhen Source Type: research
Feline infectious peritonitis virus ORF7a is a virulence factor involved in inflammatory pathology in cats
Antiviral Res. 2024 Jan 2:105794. doi: 10.1016/j.antiviral.2024.105794. Online ahead of print.ABSTRACTA hyperinflammatory response is a prominent feature of feline infectious peritonitis (FIP), but the mechanisms behind the feline infectious peritonitis virus (FIPV)-induced cytokine storm in the host have not been clarified. Studies have shown that coronaviruses encode accessory proteins that are involved in viral replication and associated with viral virulence, the inflammatory response and immune regulation. Here, we found that FIPV ORF7a gene plays a key role in viral infection and host proinflammatory responses. The re...
Source: Antiviral Research - January 4, 2024 Category: Virology Authors: Zhe Jiao Pengpeng Wang Xiaoshuai Hu Yixi Chen Juan Xu Jintao Zhang Benyuan Wu Ruxue Luo Yuejun Shi Guiqing Peng Source Type: research
Feline infectious peritonitis virus ORF7a is a virulence factor involved in inflammatory pathology in cats
Antiviral Res. 2024 Jan 2:105794. doi: 10.1016/j.antiviral.2024.105794. Online ahead of print.ABSTRACTA hyperinflammatory response is a prominent feature of feline infectious peritonitis (FIP), but the mechanisms behind the feline infectious peritonitis virus (FIPV)-induced cytokine storm in the host have not been clarified. Studies have shown that coronaviruses encode accessory proteins that are involved in viral replication and associated with viral virulence, the inflammatory response and immune regulation. Here, we found that FIPV ORF7a gene plays a key role in viral infection and host proinflammatory responses. The re...
Source: Antiviral Research - January 4, 2024 Category: Virology Authors: Zhe Jiao Pengpeng Wang Xiaoshuai Hu Yixi Chen Juan Xu Jintao Zhang Benyuan Wu Ruxue Luo Yuejun Shi Guiqing Peng Source Type: research
Ganciclovir and maribavir cross-resistance revisited: Relative drug susceptibilities of canonical cytomegalovirus mutants
Antiviral Res. 2023 Dec 30:105792. doi: 10.1016/j.antiviral.2023.105792. Online ahead of print.ABSTRACTTherapeutic use of maribavir for human cytomegalovirus infection has renewed attention to the extent of cross-resistance with ganciclovir as the existing standard therapy. Each drug selects in vivo for a characteristic set of resistance mutations in the viral UL97 kinase gene. To improve the calibration of relative susceptibilities to each drug, genetic variants at relevant UL97 codons were extensively phenotyped using the same baseline viral clone, cell culture conditions and growth readout. Ganciclovir-selected mutation...
Source: Antiviral Research - January 1, 2024 Category: Virology Authors: Sunwen Chou Justin Watanable Source Type: research
Ganciclovir and maribavir cross-resistance revisited: Relative drug susceptibilities of canonical cytomegalovirus mutants
Antiviral Res. 2023 Dec 30:105792. doi: 10.1016/j.antiviral.2023.105792. Online ahead of print.ABSTRACTTherapeutic use of maribavir for human cytomegalovirus infection has renewed attention to the extent of cross-resistance with ganciclovir as the existing standard therapy. Each drug selects in vivo for a characteristic set of resistance mutations in the viral UL97 kinase gene. To improve the calibration of relative susceptibilities to each drug, genetic variants at relevant UL97 codons were extensively phenotyped using the same baseline viral clone, cell culture conditions and growth readout. Ganciclovir-selected mutation...
Source: Antiviral Research - January 1, 2024 Category: Virology Authors: Sunwen Chou Justin Watanable Source Type: research
Ganciclovir and maribavir cross-resistance revisited: Relative drug susceptibilities of canonical cytomegalovirus mutants
Antiviral Res. 2023 Dec 30:105792. doi: 10.1016/j.antiviral.2023.105792. Online ahead of print.ABSTRACTTherapeutic use of maribavir for human cytomegalovirus infection has renewed attention to the extent of cross-resistance with ganciclovir as the existing standard therapy. Each drug selects in vivo for a characteristic set of resistance mutations in the viral UL97 kinase gene. To improve the calibration of relative susceptibilities to each drug, genetic variants at relevant UL97 codons were extensively phenotyped using the same baseline viral clone, cell culture conditions and growth readout. Ganciclovir-selected mutation...
Source: Antiviral Research - January 1, 2024 Category: Virology Authors: Sunwen Chou Justin Watanable Source Type: research
Current state and challenges in respiratory syncytial virus drug discovery and development
Antiviral Res. 2023 Dec 29:105791. doi: 10.1016/j.antiviral.2023.105791. Online ahead of print.ABSTRACTHuman respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections (LRTI) in young children and elderly people worldwide. Recent significant progress in our understanding of the structure and function of RSV proteins has led to the discovery of several clinical candidates targeting RSV fusion and replication. These include both the development of novel small molecule interventions and the isolation of potent monoclonal antibodies. In this review, we summarize the state-of-the-art of RSV drug ...
Source: Antiviral Research - December 31, 2023 Category: Virology Authors: Gang Zou Sushan Cao Zhao Gao Junming Yie Jim Zhen Wu Source Type: research
A flexible, image-based, high-throughput platform encompassing in-depth cell profiling to identify broad-spectrum coronavirus antivirals with limited off-target effects
Antiviral Res. 2023 Dec 27:105789. doi: 10.1016/j.antiviral.2023.105789. Online ahead of print.ABSTRACTThe recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) posed a major threat to global health. Although the World Health Organization ended the public health emergency status, antiviral drugs are needed to address new variants of SARS-CoV-2 and future pandemics. To identify novel broad-spectrum coronavirus drugs, we developed a high-content imaging platform compatible with high-throughput screening. The platform is broadly applicable as it can be adapted to include various cell types, vi...
Source: Antiviral Research - December 29, 2023 Category: Virology Authors: Jordi Doijen Inha Heo Koen Temmerman Peter Vermeulen Annick Diels Steffen Jaensch Mark Burcin Nick Van den Broeck Valerie Raeymaekers Joren Peremans Katrien Konings Maxime Clement Danielle Peeters Marnix Van Loock Anil Koul Christophe Buyck Michiel Van Go Source Type: research
Next-generation bNAbs for HIV-1 cure strategies
Antiviral Res. 2023 Dec 27:105788. doi: 10.1016/j.antiviral.2023.105788. Online ahead of print.ABSTRACTDespite the ability to suppress viral replication using anti-retroviral therapy (ART), HIV-1 remains a global public health problem. Curative strategies for HIV-1 have to target and eradicate latently infected cells across the body, i.e. the viral reservoir. Broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope glycoprotein (Env) have the capacity to neutralize virions and bind to infected cells to initiate elimination of these cells. To improve the efficacy of bNAbs in terms of viral suppression and viral ...
Source: Antiviral Research - December 29, 2023 Category: Virology Authors: A I Schriek Y L T Aldon M J van Gils S W de Taeye Source Type: research
