Bioscience Evidence 2024, Vol.14, No.5, 227-237 http://bioscipublisher.com/index.php/be 228 analysis of specific ASFV proteins that could serve as targets for antiviral drug development. By achieving these objectives, this research seeks to contribute to the ongoing efforts to develop effective therapeutic strategies against ASFV, ultimately aiding in the control and prevention of ASF outbreaks. 2 ASFV Genome: Structure and Function 2.1 Detailed description of ASFV genome organization The African Swine Fever Virus (ASFV) genome is a large double-stranded DNA molecule ranging from approximately 170 to 193 kilobase pairs (kbp) in length, depending on the isolate. The genome is characterized by closely spaced open reading frames (ORFs) that are read from both DNA strands. The termini of the ASFV genome are covalently closed by imperfectly base-paired hairpin loops, which exist in two complementary and inverted forms. Adjacent to these termini are inverted arrays of tandem repeats (Dixon et al., 2013). The ASFV genome encodes a variety of structural and non-structural proteins, with 68 structural proteins and over 100 non-structural proteins identified (Wang et al., 2021). The genome is organized into several multigene families (MGFs), including MGFs 100, 110, 300, 360, and 505/530, which are primarily located within the left terminal 40 kbp and right terminal 20 kbp of the genome (Dixon et al., 2013). 2.2 Key genes involved in viral replication and infection ASFV encodes numerous genes essential for its replication and infection processes. Key genes include those involved in DNA replication, transcription, and repair, such as the viral DNA polymerase, RNA polymerase, and various transcription factors (Dixon et al., 2013). The pA104R gene, encoding a histone-like protein, plays a crucial role in viral genome packaging and replication by binding to DNA and facilitating genome condensation (Liu et al., 2020; Urbano and Ferreira, 2020). Additionally, genes like A238L, which modulates NFκB and NFAT pathways, and A224L, an apoptosis inhibitor, are involved in immune evasion and virulence (Gallardo et al., 2018). The virus also encodes enzymes for base excision repair, which may help it replicate in the oxidative environment of macrophage cytoplasm (Dixon et al., 2013). 2.3 Genomic variations across ASFV strains ASFV exhibits significant genomic diversity, with variations primarily arising from the gain or loss of members of its multigene families (Dixon et al., 2013). Comparative genomic analyses have revealed an "open" pan-genome for ASFV, indicating a high level of natural diversity in its genomic composition and regulation. Of the 151-174 genes found in various ASFV strains, only 86 are considered core genes, while the rest are flexible accessory genes (Wang et al., 2020). This diversity is further highlighted by the presence of numerous single-nucleotide variations (SNVs) and structural variations, such as G-quadruplexes (G4s), which can impact gene expression and viral pathogenicity (Gong et al., 2021; Muturi et al., 2021). 2.4 Potential drug targets identified through genomic analysis Several potential drug targets have been identified through genomic and proteomic analyses of ASFV. G-quadruplexes (G4s) within the ASFV genome have been shown to be stabilizable by G4 ligands, such as N-Methyl Mesoporphyrin (NMM) and pyridostatin (PDS), which can inhibit viral replication (Muturi et al., 2021). The pA104R protein, essential for viral genome packaging, has been identified as a target for stilbene derivatives, which can disrupt its DNA binding and inhibit ASFV replication (Liu et al., 2020). Additionally, proteins involved in the endocytic pathway, such as Rab proteins, have been identified as potential targets due to their role in ASFV infection (García-Dorival et al., 2023). These findings highlight the potential of targeting specific genomic and proteomic elements of ASFV for antiviral drug development. 3 Proteomic Analysis of ASFV 3.1 Overview of ASFV proteome African swine fever virus (ASFV) encodes more than 150 proteins, many of which have unknown functions. Proteomic studies have been instrumental in identifying and characterizing these proteins, providing insights into their roles in the viral lifecycle and host interactions (Figure 1). For instance, high-throughput proteomic analysis has been used to elucidate the interactome of key ASFV proteins involved in critical infection steps, such as
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