METHODS: To understand the genetic diversity, 74 DENV-2 strains were isolated from DF epidemic cases between 2017 and 2019. Combining whole genome sequencing (WGS) technology, additional phylogenetic, haplotype, amino acid (AA) substitution, and recombination analyses were performed.
RESULTS: The results revealed that strains from 2017 were closely related to those from Singapore, Malaysia, and Thailand, indicating an imported international transmission. Local strains from 2018 were clustered with those recovered from 2019 and were closely associated with Guangzhou isolates, suggesting a within-country transmission after the significant outbreak in 2017. Compared to DENV-2 virus P14337 (Thailand/0168/1979), a total of 20 AA substitutions were detected. Notably, V431I, T2881I, and K3291T mutations only occurred in indigenous cases from 2017, and A1402T, V1457I, Q2777E, R3189K, and Q3310R mutations were exclusively found in imported cases from 2018 to 2019. The recombination analysis indicated that a total of 14 recombination events were observed.
CONCLUSION: This study may improve our understanding of DENV transmission in Hangzhou and provide further insight into DENV-2 transmission and the local vaccine choice.
METHODS: An organic ethyl acetate extract of Penicillium verruculosum sponge-derived endophytic fungi from Spongia officinalis yielded seven different secondary metabolites which are purified through HPLC. The isolated compounds are of averufin (1), aspergilol-A (2), sulochrin (3), monomethyl sulochrin (4), methyl emodin (5), citreorosein (6), and diorcinol (7). All the seven isolated compounds were characterized by high-resolution NMR spectral studies. All isolated compounds', such as anticancer, antimicrobial, anti-tuberculosis, and antiviral, were subjected to bioactivity screening.
RESULTS: Out of seven tested compounds, compound (1) exhibits strong anticancer activity toward myeloid leukemia. HL60 cell lines have an IC50 concentration of 1.00μm, which is nearly significant to that of the standard anticancer drug taxol. A virtual computational molecular docking approach of averufin with HL60 antigens revealed that averufin binds strongly with the protein target alpha, beta-tubulin (1JFF), with a -10.98 binding score. Consecutive OSIRIS and Lipinski ADME pharmacokinetic validation of averufin with HL60 antigens revealed that averufin has good pharmacokinetic properties such as drug score, solubility, and mutagenic nature. Furthermore, aspergilol-A (2) is the first report on the Penicillium verruculosum fungal strain.
DISCUSSION: We concluded that averufin (1) isolated from Penicillium verruculosum can be taken for further preliminary clinical trials like animal model in-vivo studies and pharmacodynamic studies. A future prospect of in-vivo anticancer screening of averufin can be validated through the present experimental findings.