Dataset Information

In silico identification of multi-target inhibitors from medicinal fungal metabolites against the base excision repair pathway proteins of African swine fever virus.

ABSTRACT: African swine fever virus (ASFV) has emerged as a serious threat to the pork industry resulting in significant economic losses and heightened concerns about food security. With no known cure presently available, existing control measures center on animal quarantine and culling. Considering the severity and challenges posed by ASFV, it is imperative to discover new treatment strategies and implement additional measures to prevent its further spread. This study recognized the potential of 1830 fungal metabolites from medicinal fungi as antiviral compounds against base excision repair (BER) proteins of ASFV, specifically ASFVAP, ASFVPolX, and ASFVLig. A wide array of computer-aided drug discovery techniques were employed to carry out the virtual screening process: ADMET profiling revealed 319 molecules with excellent bioavailability and toxicity properties; consensus docking identified the 10 best-scoring ligands against all targets; molecular dynamics simulation elucidated the stability of the protein-ligand complexes; and MM/PB(GB)SA energy calculations predicted the binding energies of the compounds as well as the key residues integral to binding. Through in silico methods, we identified two theoretical lead candidates against ASFVAP, four against ASFVLig, and five against ASFVPolX. Two compounds, methyl ganoderate E and antcamphin M, exhibited potential multi-target inhibitory characteristics against ASFVPolX and ASFVLig, while compound cochlactone A showed promising antagonistic results against all three BER proteins. It is recommended to prioritize these hit compounds in future in vitro and in vivo studies to validate their potential as antiviral drugs against ASFV.

SUBMITTER: Macalalad MAB

PROVIDER: S-EPMC10964135 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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<i>In silico</i> identification of multi-target inhibitors from medicinal fungal metabolites against the base excision repair pathway proteins of African swine fever virus.

Macalalad Mark Andrian B MAB Orosco Fredmoore L FL

RSC advances 20240326 14

African swine fever virus (ASFV) has emerged as a serious threat to the pork industry resulting in significant economic losses and heightened concerns about food security. With no known cure presently available, existing control measures center on animal quarantine and culling. Considering the severity and challenges posed by ASFV, it is imperative to discover new treatment strategies and implement additional measures to prevent its further spread. This study recognized the potential of 1830 fun ...[more]

PMID: 38533097

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Project description:Recently moderate-virulence classical swine fever virus (CSFV) strains have been proven capable of generating postnatal persistent infection (PI), defined by the maintenance of viremia and the inability to generate CSFV-specific immune responses in animals. These animals also showed a type I interferon blockade in the absence of clinical signs. In this study, we assessed the infection generated in 7-week-old CSFV PI wild boars after infection with the African swine fever virus (ASFV). The wild boars were divided in two groups and were infected with ASFV. Group A comprised boars who were CSFV PI in a subclinical form and Group B comprised pestivirus-free wild boars. Some relevant parameters related to CSFV replication and the immune response of CSFV PI animals were studied. Additionally, serum soluble factors such as IFN-α, TNF-α, IL-6, IL-10, IFN-γ and sCD163 were analysed before and after ASFV infection to assess their role in disease progression.After ASFV infection, only the CSFV PI wild boars showed progressive acute haemorrhagic disease; however, the survival rates following ASFV infection was similar in both experimental groups. Notwithstanding, the CSFV RNA load of CSFV PI animals remained unaltered over the study; likewise, the ASFV DNA load detected after infection was similar between groups. Interestingly, systemic type I FN-α and IL-10 levels in sera were almost undetectable in CSFV PI animals, yet detectable in Group B, while detectable levels of IFN-γ were found in both groups. Finally, the flow cytometry analysis showed an increase in myelomonocytic cells (CD172a+) and a decrease in CD4+ T cells in the PBMCs from CSFV PI animals after ASFV infection.Our results showed that the immune response plays a role in the progression of disease in CSFV subclinically infected wild boars after ASFV infection, and the immune response comprised the systemic type I interferon blockade. ASFV does not produce any interference with CSFV replication, or vice versa. ASFV infection could be a trigger factor for the disease progression in CSFV PI animals, as their survival after ASFV was similar to that of the pestivirus-free ASFV-infected group. This fact suggests a high resistance in CSFV PI animals even against a virus like ASFV; this may mean that there are relevant implications for CSF control in endemic countries. The diagnosis of ASFV and CSFV co-infection in endemic countries cannot be ruled out and need to be studied in greater depth.

Dataset Information

In silico identification of multi-target inhibitors from medicinal fungal metabolites against the base excision repair pathway proteins of African swine fever virus.

Publications

<i>In silico</i> identification of multi-target inhibitors from medicinal fungal metabolites against the base excision repair pathway proteins of African swine fever virus.

Similar Datasets

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