Bioscience Evidence 2024, Vol.14, No.5, 227-237 http://bioscipublisher.com/index.php/be 230 Two-Dimensional Electrophoresis: This technique separates proteins based on their isoelectric point and molecular weight, allowing for the identification of differentially expressed proteins in ASFV-infected cells (Alfonso et al., 2004). Matrix-Assisted Laser Desorption/Ionization (MALDI) Peptide Mass Fingerprinting: This method is used to identify proteins by matching the mass of peptide fragments to known protein databases (Alfonso et al., 2004). 3.3 Functional classification of ASFV proteins ASFV proteins have been functionally classified based on their roles in various molecular pathways and cellular processes. For example: Membrane Trafficking and Lipid Metabolism: ASFV proteins such as P34 and E199L interact with Rab proteins, which are crucial regulators of the endocytic pathway, necessary for ASFV infection (García-Dorival et al., 2023). Intracellular and Golgi Vesicle Transport: Proteins involved in these pathways have been identified as interacting partners of ASFV fusion proteins, suggesting their role in the viral lifecycle (García-Dorival et al., 2023). Redox-Related Proteins and Heat Shock Proteins: These proteins are significantly altered in ASFV-infected cells, indicating their involvement in the cellular response to infection (Alfonso et al., 2004). 3.4 Identification of essential proteins involved in viral lifecycle Proteomic studies have identified several essential ASFV proteins that play critical roles in the viral lifecycle. For instance: Fusion Proteins (P34, E199L, MGF360-15R, E248R): These proteins are involved in the fusion and endosomal exit of virions, a critical step in the ASFV infection cycle. Their interacting partners include proteins involved in membrane trafficking and lipid metabolism, which are essential for viral entry and replication (García-Dorival et al., 2023). Proteins Involved in Apoptosis and Transcriptional Modulation: Cellular proteins such as nucleoside diphosphate kinases and members of the Ran-Gppnhp-Ranbd1 complex are modified in response to ASFV infection, suggesting their roles in viral pathogenesis and host cell manipulation (Alfonso et al., 2004). By leveraging these proteomic techniques and analyses, researchers have gained valuable insights into the ASFV proteome, identifying potential therapeutic targets and advancing our understanding of the virus's interaction with host cells. 4 ASFV Proteins as Drug Targets 4.1 Criteria for selecting ASFV proteins as drug targets The selection of African Swine Fever Virus (ASFV) proteins as drug targets is guided by several critical criteria. Firstly, the protein must play a pivotal role in the virus's life cycle, such as being essential for viral replication, assembly, or evasion of the host immune response. For instance, the pS273R protease is crucial for the proteolysis of viral polyproteins, making it a prime target for antiviral drugs (Lu et al., 2023). Additionally, proteins involved in the virus's ability to evade the host's immune system, such as those interfering with the interferon (IFN) response, are also considered valuable targets. The ASFV A276R, A528R, and I329L genes have been identified to inhibit various aspects of the IFN response, highlighting their potential as drug targets (Correia et al., 2013; Correia et al., 2023). Another criterion is the protein's structural and functional uniqueness, which reduces the likelihood of off-target effects on host proteins. For example, the identification of G-Quadruplexes (G4s) in the ASFV genome, which can be stabilized by specific ligands, offers a novel target that is distinct from host cellular mechanisms (Muturi et al., 2021). Furthermore, the protein's amenability to high-throughput screening and drug design, such as the ability to perform virtual screening and molecular dynamics simulations, is also a key consideration. This approach has been successfully applied to identify potential inhibitors of the pS273R protease (Lu et al., 2023).
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