scholarly journals Prediction of antiviral drugs against African Swine Fever Viruses based on protein-protein interaction analysis

2019 ◽  
Author(s):  
Zhaozhong Zhu ◽  
Yunshi Fan ◽  
Zena Cai ◽  
Zheng Zhang ◽  
Congyu Lu ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Interaction Analysis ◽  
African Swine Fever Virus ◽  
Antiviral Drug ◽  
African Swine Fever ◽  
High Specificity ◽  
Antiviral Drugs ◽  
Multiple Sources ◽  
Swine Industry ◽  
Spectrum Effect

AbstractThe African swine fever virus (ASFV) has severely influenced the swine industry of the world. Unfortunately, there is no effective antiviral drug or vaccine against the virus until now. Identification of new anti-ASFV drugs is urgently needed. Here, an up-to-date set of protein-protein interactions (PPIs) between ASFV and swine were curated by integration of PPIs from multiple sources. Thirty-two swine proteins were observed to interact with ASFVs and were defined as AIPs. They were found to play a central role in the swine PPI network, with significant larger degree, betweenness and smaller shortest path length than other swine proteins. Some of AIPs also interacted with several other viruses and could be taken as potential targets of drugs for broad-spectrum effect, such as HSP90AB1. Finally, the antiviral drugs which targeted AIPs and ASFV proteins were predicted. Several drugs with either broad-spectrum effect or high specificity on AIPs were identified, such as Polaprezinc. This work could not only deepen our understanding towards the ASFV-swine interactions, but also help for the development of effective antiviral drugs against the ASFVs.

scholarly journals Prediction of antiviral drugs against African swine fever viruses based on protein–protein interaction analysis

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8855
Author(s):  
Zhaozhong Zhu ◽  
Yunshi Fan ◽  
Yang Liu ◽  
Taijiao Jiang ◽  
Yang Cao ◽  
...  
Keyword(s):  
Protein Interaction ◽  
Protein Interactions ◽  
Broad Spectrum ◽  
Antiviral Drug ◽  
African Swine Fever ◽  
Antiviral Drugs ◽  
Dynamics Simulation ◽  
Protein Protein Interactions ◽  
Protein Protein Interaction ◽  
Spectrum Effect

The African swine fever virus (ASFV) has severely influenced the swine industry of the world. Unfortunately, there is currently no effective antiviral drug or vaccine against the virus. Identification of new anti-ASFV drugs is urgently needed. Here, an up-to-date set of protein–protein interactions between ASFV and swine were curated by integration of protein–protein interactions from multiple sources. Thirty-eight swine proteins were observed to interact with ASFVs and were defined as ASFV-interacting swine proteins. The ASFV-interacting swine proteins were found to play a central role in the swine protein–protein interaction network, with significant larger degree, betweenness and smaller shortest path length than other swine proteins. Some of ASFV-interacting swine proteins also interacted with several other viruses and could be taken as potential targets of drugs for broad-spectrum effect, such as HSP90AB1. Finally, the antiviral drugs which targeted ASFV-interacting swine proteins and ASFV proteins were predicted. Several drugs with either broad-spectrum effect or high specificity on ASFV-interacting swine proteins were identified, such as Polaprezinc and Geldanamycin. Structural modeling and molecular dynamics simulation showed that Geldanamycin could bind with swine HSP90AB1 stably. This work could not only deepen our understanding towards the ASFV-swine interactions, but also help for the development of effective antiviral drugs against the ASFVs.

scholarly journals Identification of African Swine Fever Virus Inhibitors through High Performance Virtual Screening Using Machine Learning

2021 ◽  
Vol 22 (24) ◽  
pp. 13414
Author(s):  
Jiwon Choi ◽  
Dongseob Tark ◽  
Yun-Sook Lim ◽  
Soon B. Hwang
Keyword(s):  
Machine Learning ◽  
High Performance ◽  
African Swine Fever Virus ◽  
Antiviral Drug ◽  
African Swine Fever ◽  
Principal Component ◽  
Antiviral Drugs ◽  
Fever Virus ◽  
Scoring Functions

African swine fever virus (ASFV) is a highly contagious virus that causes severe hemorrhagic viral disease resulting in high mortality in domestic and wild pigs, until few antiviral agents can inhibit ASFV infections. Thus, new anti-ASFV drugs need to be urgently identified. Recently, we identified pentagastrin as a potential antiviral drug against ASFVs using molecular docking and machine learning models. However, the scoring functions are easily influenced by properties of protein pockets, resulting in a scoring bias. Here, we employed the 5′-P binding pocket of AsfvPolX as a potential binding site to identify antiviral drugs and classified 13 AsfvPolX structures into three classes based on pocket parameters calculated by the SiteMap module. We then applied principal component analysis to eliminate this scoring bias, which was effective in making the SP Glide score more balanced between 13 AsfvPolX structures in the dataset. As a result, we identified cangrelor and fostamatinib as potential antiviral drugs against ASFVs. Furthermore, the classification of the pocket properties of AsfvPolX protein can provide an alternative approach to identify novel antiviral drugs by optimizing the scoring function of the docking programs. Here, we report a machine learning-based novel approach to generate high binding affinity compounds that are individually matched to the available classification of the pocket properties of AsfvPolX protein.

scholarly journals Prediction of African Swine Fever Virus Inhibitors by Molecular Docking-Driven Machine Learning Models

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3592
Author(s):  
Jiwon Choi ◽  
Jun Seop Yun ◽  
Hyeeun Song ◽  
Yong-Keol Shin ◽  
Young-Hoon Kang ◽  
...  
Keyword(s):  
Machine Learning ◽  
Molecular Docking ◽  
African Swine Fever Virus ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
African Swine Fever ◽  
Antiviral Drugs ◽  
Fever Virus ◽  
Learning Models ◽  
Machine Learning Models

African swine fever virus (ASFV) causes a highly contagious and severe hemorrhagic viral disease with high mortality in domestic pigs of all ages. Although the virus is harmless to humans, the ongoing ASFV epidemic could have severe economic consequences for global food security. Recent studies have found a few antiviral agents that can inhibit ASFV infections. However, currently, there are no vaccines or antiviral drugs. Hence, there is an urgent need to identify new drugs to treat ASFV. Based on the structural information data on the targets of ASFV, we used molecular docking and machine learning models to identify novel antiviral agents. We confirmed that compounds with high affinity present in the region of interest belonged to subsets in the chemical space using principal component analysis and k-means clustering in molecular docking studies of FDA-approved drugs. These methods predicted pentagastrin as a potential antiviral drug against ASFVs. Finally, it was also observed that the compound had an inhibitory effect on AsfvPolX activity. Results from the present study suggest that molecular docking and machine learning models can play an important role in identifying potential antiviral drugs against ASFVs.

scholarly journals Deletion of the L7L-L11L Genes Attenuates ASFV and Induces Protection against Homologous Challenge

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 255
Author(s):  
Jingyuan Zhang ◽  
Yanyan Zhang ◽  
Teng Chen ◽  
Jinjin Yang ◽  
Huixian Yue ◽  
...  
Keyword(s):  
African Swine Fever Virus ◽  
Clinical Signs ◽  
African Swine Fever ◽  
Biological Properties ◽  
High Dose ◽  
Swine Industry ◽  
Epidemic Disease ◽  
Intramuscular Inoculation ◽  
Homologous Challenge

African swine fever (ASF), caused by the African swine fever virus (ASFV), is a major epidemic disease endangering the swine industry. Although a number of vaccine candidates have been reported, none are commercially available yet. To explore the effect of unknown genes on the biological characteristics of ASFV and the possibility of a gene-deleted isolate as a vaccine candidate, the strain SY18ΔL7-11, with deletions of L7L–L11L genes from ASFV SY18, was constructed, and its biological properties were analyzed. The results show that deletion of genes L7L-L11L did not affect replication of the virus in vitro. Virulence of SY18△L7-11 was significantly reduced, as 11 of the 12 pigs survived for 28 days after intramuscular inoculation with a low dose (103 TCID50) or a high dose (106 TCID50) of SY18ΔL7-11. All 11 surviving pigs were completely protected against challenge with the parental ASFV SY18 on 28 days postinoculation (dpi). Transient fever and/or irregularly low levels of genomic DNA in the blood were monitored in some pigs after inoculation. No ASF clinical signs or viremia were monitored after challenge. Antibodies to ASFV were induced in all pigs from 14 to 21 days postinoculation. IFN-γ was detected in most of the inoculated pigs, which is usually inhibited in ASFV-infected pigs. Overall, the results demonstrate that SY18ΔL7-11 is a candidate for further constructing safer vaccine(s), with better joint deletions of other gene(s) related to virulence.

scholarly journals BA71ΔCD2: a New Recombinant Live Attenuated African Swine Fever Virus with Cross-Protective Capabilities

2017 ◽  
Vol 91 (21) ◽  
Author(s):  
Paula L. Monteagudo ◽  
Anna Lacasta ◽  
Elisabeth López ◽  
Laia Bosch ◽  
Javier Collado ◽  
...  
Keyword(s):  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Fever Virus ◽  
Sub Saharan Africa ◽  
Swine Industry ◽  
Lethal Challenge ◽  
Major Threat ◽  
Attenuated Viruses ◽  
Genotype Ii

ABSTRACT African swine fever is a highly contagious viral disease of mandatory declaration to the World Organization for Animal Health (OIE). The lack of available vaccines makes its control difficult; thus, African swine fever virus (ASFV) represents a major threat to the swine industry. Inactivated vaccines do not confer solid protection against ASFV. Conversely, live attenuated viruses (LAV), either naturally isolated or obtained by genetic manipulation, have demonstrated reliable protection against homologous ASFV strains, although little or no protection has been demonstrated against heterologous viruses. Safety concerns are a major issue for the use of ASFV attenuated vaccine candidates and have hampered their implementation in the field so far. While trying to develop safer and efficient ASFV vaccines, we found that the deletion of the viral CD2v (EP402R) gene highly attenuated the virulent BA71 strain in vivo. Inoculation of pigs with the deletion mutant virus BA71ΔCD2 conferred protection not only against lethal challenge with the parental BA71 but also against the heterologous E75 (both genotype I strains). The protection induced was dose dependent, and the cross-protection observed in vivo correlated with the ability of BA71ΔCD2 to induce specific CD8+ T cells capable of recognizing both BA71 and E75 viruses in vitro. Interestingly, 100% of the pigs immunized with BA71ΔCD2 also survived lethal challenge with Georgia 2007/1, the genotype II strain of ASFV currently circulating in continental Europe. These results open new avenues to design ASFV cross-protective vaccines, essential to fight ASFV in areas where the virus is endemic and where multiple viruses are circulating. IMPORTANCE African swine fever virus (ASFV) remains enzootic in most countries of Sub-Saharan Africa, today representing a major threat for the development of their swine industry. The uncontrolled presence of ASFV has favored its periodic exportation to other countries, the last event being in Georgia in 2007. Since then, ASFV has spread toward neighboring countries, reaching the European Union's east border in 2014. The lack of available vaccines against ASFV makes its control difficult; so far, only live attenuated viruses have demonstrated solid protection against homologous experimental challenges, but they have failed at inducing solid cross-protective immunity against heterologous viruses. Here we describe a new LAV candidate with unique cross-protective abilities: BA71ΔCD2. Inoculation of BA71ΔCD2 protected pigs not only against experimental challenge with BA71, the virulent parental strain, but also against heterologous viruses, including Georgia 2007/1, the genotype II strain of ASFV currently circulating in Eastern Europe.

scholarly journals Risk of African swine fever virus introduction into the United States through smuggling of pork in air passenger luggage

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Cristina Jurado ◽  
Lina Mur ◽  
María Sol Pérez Aguirreburualde ◽  
Estefanía Cadenas-Fernández ◽  
Beatriz Martínez-López ◽  
...  
Keyword(s):  
Western Europe ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
The United States ◽  
Economic Losses ◽  
Swine Industry ◽  
Virus Surveillance ◽  
Global Epidemiology ◽  
The Us ◽  
Mean Risk

Abstract African swine fever causes substantial economic losses in the swine industry in affected countries. Traditionally confined to Africa with only occasional incursions into other regions, ASF began spreading into Caucasian countries and Eastern Europe in 2007, followed by Western Europe and Asia in 2018. Such a dramatic change in the global epidemiology of ASF has resulted in concerns that the disease may continue to spread into disease-free regions such as the US. In this study, we estimated the risk of introduction of ASF virus into the US through smuggling of pork in air passenger luggage. Results suggest that the mean risk of ASFV introduction into the US via this route has increased by 183.33% from the risk estimated before the disease had spread into Western Europe or Asia. Most of the risk (67.68%) was associated with flights originating from China and Hong Kong, followed by the Russian Federation (26.92%). Five US airports accounted for >90% of the risk. Results here will help to inform decisions related to the design of ASF virus surveillance strategies in the US.

scholarly journals A Simple Method for Sample Preparation to Facilitate Efficient Whole-Genome Sequencing of African Swine Fever Virus

Viruses ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1129 ◽  
Author(s):  
Ferenc Olasz ◽  
István Mészáros ◽  
Szilvia Marton ◽  
Győző L. Kaján ◽  
Vivien Tamás ◽  
...  
Keyword(s):  
Sample Preparation ◽  
African Swine Fever Virus ◽  
Animal Health ◽  
African Swine Fever ◽  
Fever Virus ◽  
Whole Genome ◽  
Swine Industry ◽  
Viral Dna ◽  
Simple Method ◽  
Generation Sequencing

In the recent years, African swine fever has become the biggest animal health threat to the swine industry. To facilitate quick genetic analysis of its causative agent, the African swine fever virus (ASFV), we developed a simple and efficient method for next generation sequencing of the viral DNA. Execution of the protocol does not demand complicated virus purification steps, enrichment of the virus by ultracentrifugation or of the viral DNA by ASFV-specific PCRs, and minimizes the use of Sanger sequencing. Efficient DNA-se treatment, monitoring of sample preparation by qPCR, and whole genome amplification are the key elements of the method. Through detailed description of sequencing of the first Hungarian ASFV isolate (ASFV_HU_2018), we specify the sensitive steps and supply key reference numbers to assist reproducibility and to facilitate the successful use of the method for other ASFV researchers.

scholarly journals Estimation of the transmission dynamics of African swine fever virus within a swine house

2017 ◽  
Vol 145 (13) ◽  
pp. 2787-2796 ◽  
Author(s):  
J. P. NIELSEN ◽  
T. S. LARSEN ◽  
T. HALASA ◽  
L. E. CHRISTIANSEN
Keyword(s):  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Simulation Models ◽  
Fever Virus ◽  
Economic Consequences ◽  
Estimation Of Parameters ◽  
Swine Industry ◽  
Transmission Parameters ◽  
The Individual ◽  
The Impact

SUMMARYThe spread of African swine fever virus (ASFV) threatens to reach further parts of Europe. In countries with a large swine production, an outbreak of ASF may result in devastating economic consequences for the swine industry. Simulation models can assist decision makers setting up contingency plans. This creates a need for estimation of parameters. This study presents a new analysis of a previously published study. A full likelihood framework is presented including the impact of model assumptions on the estimated transmission parameters. As animals were only tested every other day, an interpretation was introduced to cover the weighted infectiousness on unobserved days for the individual animals (WIU). Based on our model and the set of assumptions, the within- and between-pen transmission parameters were estimated to βw = 1·05 (95% CI 0·62–1·72), βb = 0·46 (95% CI 0·17–1·00), respectively, and the WIU = 1·00 (95% CI 0–1). Furthermore, we simulated the spread of ASFV within a pig house using a modified SEIR-model to establish the time from infection of one animal until ASFV is detected in the herd. Based on a chosen detection limit of 2·55% equivalent to 10 dead pigs out of 360, the disease would be detected 13–19 days after introduction.

scholarly journals Genetic characterisation of African swine fever virus from 2017 outbreaks in Zambia: Identification of p72 genotype II variants in domestic pigs

2018 ◽  
Vol 85 (1) ◽  
Author(s):  
Edgar Simulundu ◽  
Yona Sinkala ◽  
Herman M. Chambaro ◽  
Andrew Chinyemba ◽  
Frank Banda ◽  
...  
Keyword(s):  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Variable Region ◽  
Economic Losses ◽  
African Region ◽  
Swine Industry ◽  
African Countries ◽  
Central Variable Region ◽  
Close Relationship ◽  
Haemorrhagic Disease

African swine fever (ASF) is a contagious haemorrhagic disease associated with causing heavy economic losses to the swine industry in many African countries. In 2017, Zambia experienced ASF outbreaks in Mbala District (Northern province) and for the first time in Isoka and Chinsali districts (Muchinga province). Meanwhile, another outbreak was observed in Chipata District (Eastern province). Genetic analysis of part of the B646L gene, E183L gene, CP204L gene and the central variable region of the B602L gene of ASF virus (ASFV) associated with the outbreaks in Mbala and Chipata districts was conducted. The results revealed that the ASFV detected in Mbala District was highly similar to that of the Georgia 2007/1 isolate across all the genome regions analysed. In contrast, while showing close relationship with the Georgia 2007/1 virus in the B646L gene, the ASFV detected in Chipata District showed remarkable genetic variation in the rest of the genes analysed. These results suggest that the Georgia 2007/1-like virus could be more diverse than what was previously thought, underscoring the need of continued surveillance and monitoring of ASFVs within the south-eastern African region to better understand their epidemiology and the relationships between outbreaks and their possible origin.

scholarly journals Rapid and sensitive RPA-Cas12a-fluorescence assay for point-of-care detection of African swine fever virus

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254815
Author(s):  
Jinyu Fu ◽  
Yueping Zhang ◽  
Guang Cai ◽  
Geng Meng ◽  
Shuobo Shi
Keyword(s):  
African Swine Fever Virus ◽  
Point Of Care ◽  
African Swine Fever ◽  
High Sensitivity ◽  
Fluorescence Assay ◽  
Fever Virus ◽  
Diagnostic Methods ◽  
High Morbidity ◽  
Swine Industry ◽  
Control And Prevention

African swine fever (ASF) is a serious contagious disease that causes fatal haemorrhagic fever in domestic and wild pigs, with high morbidity. It has caused devastating damage to the swine industry worldwide, necessitating the focus of attention on detection of the ASF pathogen, the African swine fever virus (ASFV). In order to overcome the disadvantages of conventional diagnostic methods (e.g. time-consuming, demanding and unintuitive), quick detection tools with higher sensitivity need to be explored. In this study, based on the conserved p72 gene sequence of ASFV, we combined the Cas12a-based assay with recombinase polymerase amplification (RPA) and a fluorophore-quencher (FQ)-labeled reporter assay for rapid and visible detection. Five crRNAs designed for Cas12a-based assay showed specificity with remarkable fluorescence intensity under visual inspection. Within 20 minutes, with an initial concentration of two copies of DNA, the assay can produce significant differences between experimental and negative groups, indicating the high sensitivity and rapidity of the method. Overall, the developed RPA-Cas12a-fluorescence assay provides a fast and visible tool for point-of-care ASFV detection with high sensitivity and specificity, which can be rapidly performed on-site under isothermal conditions, promising better control and prevention of ASF.

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