Article
Immunology
Huimei Cui, Jinke Yang, Bo Yang, Yu Hao, Xijuan Shi, Dajun Zhang, Ting Zhang, DengShuai Zhao, Xingguo Yuan, Xuehui Chen, Xiangtao Liu, Haixue Zheng, Keshan Zhang
Summary: African swine fever (ASF) is a highly infectious disease caused by ASFV, with a high mortality rate and serious socioeconomic consequences worldwide. This study used the virtual screening software PyRx to screen compounds against the drug target D1133L, identifying periactin as a candidate drug. Periactin showed little cytotoxicity and dose-dependently inhibited ASFV replication in vitro. Further research demonstrated periactin's ability to down-regulate D1133L at the transcriptional and protein levels. This study provides important candidate drugs for ASF prevention and treatment, as well as new perspectives for ASFV vaccine and drug development.
MICROBIAL PATHOGENESIS
(2023)
Article
Biochemistry & Molecular Biology
Chenliang Zhang, Qiulin Tang, Hongwei Xia, Huanji Xu, Feng Bi
Summary: Protein aggregation and degradation via autophagy (aggrephagy) are important cellular mechanisms to remove misfolded polypeptides when proteasome function is impaired. A protein complex consisting of heat shock protein 70 (Hsp70), cochaperone CHIP, and co-chaperone BAG3 has been shown to be involved in activating protein aggregation. However, the specific mechanisms of how this complex functions in protein degradation are not yet well understood. This study reveals that the M2 isoform of pyruvate kinase (PKM2) promotes the aggregation of ubiquitinated proteins under proteasome stress. Knockout or knockdown of PKM2 worsens the sensitivity of cells to proteasome inhibitors. Additionally, PKM2 facilitates the interaction between BAG3, CHIP, and HSP70 upon proteasome inhibition. These findings suggest that PKM2 plays a regulatory role in the formation of the CHIP-HSP70-BAG3 complex and promotes the aggregation of ubiquitinated misfolded proteins in response to proteasome stress.
Article
Veterinary Sciences
Ruiping Wei, Xiaoying Wang, Yongchang Cao, Lang Gong, Xiaohong Liu, Guihong Zhang, Chunhe Guo
Summary: African swine fever (ASF) is a highly contagious disease with no effective vaccine or treatment. This study found that chlorine dioxide (ClO2) can strongly inhibit ASF virus replication and has anti-inflammatory properties. These findings are significant for the development of new drugs against ASF.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Article
Veterinary Sciences
ChiHai Ji, JingZhe Jiang, YingFang Wei, ZhiYuan Wang, YongJie Chen, ZhanZhuo Mai, MengKai Cai, ChenXiao Qin, Yu Cai, HeYou Yi, Guan Liang, Gang Lu, Lang Gong, GuiHong Zhang, Heng Wang
Summary: The African swine fever outbreak in China in 2018 severely damaged the pig industry in the country. The complex genome of ASFV and inadequate whole genome information highlight the importance of efficiently obtaining virus genome sequences. Our method provides an efficient way to sequence whole genomes and facilitate ASFV genome sequencing and novel virus discovery.
FRONTIERS IN VETERINARY SCIENCE
(2021)
Article
Virology
Sophie-Marie Aicher, Paul Monaghan, Christopher L. Netherton, Philippa C. Hawes
Summary: Research revealed that African swine fever virus replicates in perinuclear cytoplasmic replication sites known as viral factories, where membrane assembly intermediates accumulate into a network structure. These intermediates start as small membrane fragments in the early stages of factory formation, gradually growing and linking together to form new virions, though the specific mechanisms of membrane formation and trafficking during virus morphogenesis remain unclear.
Article
Agriculture, Dairy & Animal Science
Umberto Molini, Giovanni Franzo, Tirumala B. K. Settypalli, Maria Y. Hemberger, Siegfried Khaiseb, Giovanni Cattoli, William G. Dundon, Charles E. Lamien
Summary: Important swine pathogens, African swine fever virus (ASFV) and porcine parvovirus 1 (PPV1), were identified in warthogs in Namibia and genetically characterized in this study. The findings will be of interest to those working in swine disease management and control. Understanding virus circulation in wild animals, especially those in contact with domestic animals, is crucial for disease management and control.
Article
Cell Biology
Longlong Wang, Etori Aguiar Moreira, Georg Kempf, Yasuyuki Miyake, Blandina I. Oliveira Esteves, Amal Fahmi, Jonas Schaefer, Birgit Dreier, Yohei Yamauchi, Marco P. Alves, Andreas Plueckthun, Patrick Matthias
Summary: The deacetylase HDAC6 has tandem catalytic domains and a zinc finger domain binding ubiquitin, which promotes the formation of aggresomes and stress granules. Influenza A virus subverts this pathway to facilitate infection. Designed ankyrin repeat proteins (DARPins) targeting the ZnF can impair viral infection and reduce the formation of SGs and aggresomes.
Article
Microbiology
Su Li, Hailiang Ge, Yanhua Li, Kehui Zhang, Shaoxiong Yu, Hongwei Cao, Yanjin Wang, Hao Deng, Jiaqi Li, Jingwen Dai, Lian-Feng Li, Yuzi Luo, Yuan Sun, Zhi Geng, Yuhui Dong, Heng Zhang, Hua-Ji Qiu
Summary: In this study, the researchers revealed the function of pE301R as a sliding clamp in ASFV genomic replication. They showed that pE301R interacts with the ASFV genome and viral DNA polymerase, and affects virus replication.
Review
Biology
Zhaoyao Li, Wenxian Chen, Zilong Qiu, Yuwan Li, Jindai Fan, Keke Wu, Xiaowen Li, Mingqiu Zhao, Hongxing Ding, Shuangqi Fan, Jinding Chen
Summary: African swine fever is a highly fatal viral disease in domestic pigs and wild boars, impacting pig-raising countries and pork trade. Safe and effective vaccines are urgently needed to control outbreaks. Understanding the structure, function, immune response, and diagnosis of the ASF virus is crucial for vaccine development.
Article
Immunology
Siqi Cai, Zezhong Zheng, JiaoJiao Cheng, Lintao Zhong, Ran Shao, Feiyan Zheng, Zhiying Lai, Jiajun Ou, Liang Xu, Pei Zhou, Gang Lu, Guihong Zhang
Summary: This study identified swine interferon-induced transmembrane proteins (SwIFITMs) as having potent antiviral activity against African swine fever virus (ASFV). These proteins were found to be constitutively expressed in most porcine tissues and their expression levels were induced by ASFV infection or swine interferon treatment. Overexpression of SwIFITMs inhibited ASFV replication in Vero cells, while knockdown of these genes enhanced ASFV replication in PAMs. The study also demonstrated that endogenous IFITMs play a role in restricting ASFV replication. Overall, this research expands our understanding of the antiviral activity of porcine IFITMs against ASFV.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Agronomy
Elzbieta Jadwiga Szymanska, Mariusz Dziwulaki
Summary: African swine fever poses a major problem in pig production in Poland, with wild boars and human activity being the main causes of virus transmission. This research shows that the disease has a certain periodicity in the country, and despite actions taken, it spreads rapidly.
Review
Virology
Maria Serena Beato, Federica D'Errico, Carmen Iscaro, Stefano Petrini, Monica Giammarioli, Francesco Feliziani
Summary: African Swine Fever (ASF) is a highly lethal disease in suids that is transmitted through direct and indirect contact with infected animals and contaminated objects. The spread of ASF in Europe has revealed gaps in our understanding of transmission mechanisms. Due to the lack of vaccines, biosecurity measures and cleaning and disinfection procedures are essential for controlling the spread of ASF in pig farms.
Article
Infectious Diseases
Megan C. Niederwerder, Scott Dee, Diego G. Diel, Ana M. M. Stoian, Laura A. Constance, Matthew Olcha, Vlad Petrovan, Gilbert Patterson, Ada G. Cino-Ozuna, Raymond R. R. Rowland
Summary: African swine fever is a significant threat to global pork production, as the virus can be transmitted through contaminated feed. Research shows that feed additives based on medium-chain fatty acids and formaldehyde can reduce the infectivity of ASFV.
TRANSBOUNDARY AND EMERGING DISEASES
(2021)
Article
Virology
Yanyan Zhang, Junnan Ke, Jingyuan Zhang, Jinjin Yang, Huixian Yue, Xintao Zhou, Yu Qi, Rongnian Zhu, Faming Miao, Qian Li, Fei Zhang, Ying Wang, Xun Han, Lijuan Mi, Jinmei Yang, Shoufeng Zhang, Teng Chen, Rongliang Hu
Summary: African swine fever (ASF) is a severe infectious disease in pigs caused by ASFV, with no commercial vaccine available. A new vaccine candidate named SY18DI226R has been identified, showing promising results in eliciting immunity to virulent ASFV infection in pigs.
JOURNAL OF VIROLOGY
(2021)
Review
Microbiology
Hongliang Zhang, Saisai Zhao, Haojie Zhang, Zhihua Qin, Hu Shan, Xiulei Cai
Summary: African swine fever (ASF) is a fatal infectious disease caused by the ASF virus (ASFV). It is classified as a legally notifiable disease that must be reported to the World Organization for Animal Health. The global pig industry has suffered significant economic losses due to ASF, and controlling and eradicating the disease is crucial. Vaccination is the optimal strategy, but an effective ASF vaccine with high immunoprotective potential is still needed.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Pharmacology & Pharmacy
I Galindo, U. Garaigorta, F. Lasala, M. A. Cuesta-Geijo, P. Bueno, C. Gil, R. Delgado, P. Gastaminza, C. Alonso
Summary: The study demonstrates that drug compounds targeting endosomal membrane proteins show potent inhibitory effects on the entry of SARS-CoV-2, EBOV, and ASFV into cells, suggesting the potential of these compounds as broad-spectrum antivirals targeting the endocytic pathway proteins.
ANTIVIRAL RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Fatima Lasala, Alfonso Garcia-Rubia, Carlos Requena, Inmaculada Galindo, Miguel Angel Cuesta-Geijo, Isabel Garcia-Dorival, Paula Bueno, Nuria Labiod, Joanna Luczkowiak, Ana Martinez, Nuria E. Campillo, Covadonga Alonso, Rafael Delgado, Carmen Gil
Summary: Despite the lack of currently licensed antiviral drugs for treating Ebola virus disease, efforts are ongoing to identify new drugs to combat EBOV. Virtual screening has led to the discovery of small organic molecules with potent inhibitory action against EBOV infection, paving the way for hit to lead optimization programs toward successful candidates.
ANTIVIRAL RESEARCH
(2021)
Article
Virology
Lucia Barrado-Gil, Ana del Puerto, Inmaculada Galindo, Miguel Angel Cuesta-Geijo, Isabel Garcia-Dorival, Carlos Maluquer de Motes, Covadonga Alonso
Summary: The African swine fever virus early protein UBCv1 has been found to modulate innate immune response by targeting NF-kappa B and AP-1 pathways. Its inhibitory activity acts upstream at the level of IKK beta, blocking key events in NF-kappa B signaling. Despite its known ubiquitination capacity, UBCv1's immunomodulatory activity seems to be separate from this function.
Article
Pharmacology & Pharmacy
Isabel Garcia-Dorival, Miguel Angel Cuesta-Geijo, Lucia Barrado-Gil, Inmaculada Galindo, Urtzi Garaigorta, Jesus Urquiza, Ana del Puerto, Nuria E. Campillo, Ana Martinez, Pablo Gastaminza, Carmen Gil, Covadonga Alonso
Summary: The study found a novel interaction between the SARSCoV-2 nucleoprotein (N) and the cholesterol transporter NPC1, and identified compounds that can reduce viral infection, highlighting the importance of NPC1 for SARS-CoV-2 infection and suggesting a potential new therapeutic target against COVID-19.
ANTIVIRAL RESEARCH
(2021)
Article
Microbiology
Miguel Angel Cuesta-Geijo, Isabel Garcia-Dorival, Ana del Puerto, Jesus Urquiza, Inmaculada Galindo, Lucia Barrado-Gil, Fatima Lasala, Ana Cayuela, Carlos Oscar S. Sorzano, Carmen Gil, Rafael Delgado, Covadonga Alonso
Summary: The inner viral membrane proteins of African swine fever virus (ASFV) interact with endosomal proteins, potentially playing a crucial role in the viral entry process. Silencing or knockout of these proteins affects different stages of ASFV infection, and in some cases, prevents the virus from entering the cytoplasm from endosomes. These findings provide new insights into the role of endosomal proteins in ASFV infection.
Article
Biochemistry & Molecular Biology
Maria Angela Oliva, Carlota Tosat-Bitrian, Lucia Barrado-Gil, Francesca Bonato, Inmaculada Galindo, Urtzi Garaigorta, Beatriz Alvarez-Bernad, Rebeca Paris-Ogayar, Daniel Lucena-Agell, Juan Francisco Gimenez-Abian, Isabel Garcia-Dorival, Jesus Urquiza, Pablo Gastaminza, Jose Fernando Diaz, Valle Palomo, Covadonga Alonso
Summary: Microtubule targeting agents have potential in antiviral drug research, and some clinically used drugs have shown significant inhibitory effects on viral infections. However, their mechanism of action is complex and the relationship with intracellular transport is unclear.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Alfonso Garcia-Rubia, Fatima Lasala, Tiziana Ginex, Marcos Morales-Tenorio, Catherine Olal, Michelle Heung, Paola Oquist, Inmaculada Galindo, Miguel Aprimengel Cuesta-Geijo, Jose M. Casasnovas, Nuria E. Campillo, Angeles Canales, Covadonga Alonso, Ana Martinez, Cesar Munoz-Fontela, Rafael Delgado, Carmen Gil
Summary: Ebola virus (EBOV), a single-strand RNA virus in the Filoviridae family, has been responsible for significant outbreaks since 2013. In this study, a new series of compounds were synthesized and found to inhibit EBOV infection by acting as virus entry inhibitors. The compounds were evaluated for their inhibitory activity against surrogate models and replicative EBOV, and their biological target was elucidated through various experiments. Additionally, their therapeutic potential was confirmed through in vitro metabolic stability and in vivo pharmacokinetic studies.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Virology
Isabel Garcia-Dorival, Miguel angel Cuesta-Geijo, Inmaculada Galindo, Ana del Puerto, Lucia Barrado-Gil, Jesus Urquiza, Covadonga Alonso