Comparative genome analysis between Southeast Asian and South American Zika viruses

OBJECTIVE@#To understand the cause for the differences between potentially mild Southeast Asian and the more pathogenic ZIKV in South America.@*METHODS@#A comparative genomic analysis was performed to determine putative causations stemming from ZIKV.@*RESULTS@#Phylogenetic analyses integrating geographical and time factors revealed that Southeast Asian ZIKV might not be the direct source of South American outbreaks as previously speculated. Amino acid residues unique to South American ZIKV isolates at the envelope, pr and NS1 proteins are listed and shown in the structural context. These unique residues on external viral proteins are not found in Southeast Asian ZIKV and could be responsible for the ongoing outbreak either via an intrinsic property of the virus or interactions with human immunity. Only a selected few primer/probe sets currently in clinical use were identified of being capable of detecting ZIKV strains worldwide. The envelope proteins of dengue virus (DENV) and ZIKV also showed a remarkable degree of similarity especially at the surface residues.@*CONCLUSIONS@#These findings may help explain the cross-reactivity of DENV antibodies to ZIKV. Thus, major caveats must be exercised in using existing diagnostic tools for ZIKV.

Comparative genome analysis between Southeast Asian and South American Zika viruses

Objective To understand the cause for the differences between potentially mild Southeast Asian and the more pathogenic ZIKV in South America. Methods A comparative genomic analysis was performed to determine putative causations stemming from ZIKV. Results Phylogenetic analyses integrating geographical and time factors revealed that Southeast Asian ZIKV might not be the direct source of South American outbreaks as previously speculated. Amino acid residues unique to South American ZIKV isolates at the envelope, pr and NS1 proteins are listed and shown in the structural context. These unique residues on external viral proteins are not found in Southeast Asian ZIKV and could be responsible for the ongoing outbreak either via an intrinsic property of the virus or interactions with human immunity. Only a selected few primer/probe sets currently in clinical use were identified of being capable of detecting ZIKV strains worldwide. The envelope proteins of dengue virus (DENV) and ZIKV also showed a remarkable degree of similarity especially at the surface residues. Conclusions These findings may help explain the cross-reactivity of DENV antibodies to ZIKV. Thus, major caveats must be exercised in using existing diagnostic tools for ZIKV.

Antiplasmodial effects of Brucea javanica (L.) Merr. and Eurycoma longifolia Jack extracts and their combination with chloroquine and quinine on Plasmodium falciparum in culture

Fruits of <I>Brucea javanica</I> (L.) Merr. (“Ratchadad” in Thai) and roots of <I>Eurycoma longifolia</I> Jack (“Plalaipeag” in Thai) are used as traditional medicines for the treatment of malarial fever. Ethanol, methanol, ethyl acetate, ethyl alcohol and aqueous extracts were tested against the multidrug-resistant <I>Plasmodium falciparum</I> strain K1. Ethanol and methanol-ethanol extracts, together with methanol residue, from fruits of <I>B. javanica</I> (L.) Merr. showed the highest antiplasmodial activities with IC<SUB>50</SUB> values of 0.5 ± 0.3, 0.3 ± 0.1 and 0.3 ± 0.05 Μg⁄mL, respectively, comparable to the IC<SUB>50</SUB> values of chloroquine (0.17 ± 0.02 Μg⁄mL) and quinine (0.3 ± 0.1 Μg⁄mL). Similarly, ethanol and methanol-ethanol extracts of roots of <I>E. longifolia</I> Jack showed higher activities than those of the other solvent extracts, but their activities were about 10-fold lower than those of extracts from <I>B. javanica</I> (L.) Merr. fruit. In drug combination tests, <I>B. javanica</I> (L.) Merr. and <I>E. longifolia</I> Jack extracts did not appear to antagonize antiplasmodial activity of chloroquine and quinine. Not only well-known quassinoid glycosides but also coumarins and flavonoids identified by thin-layer chromatography in ethanol and methanol-ethanol extracts and in methanol residue of <I>B. javanica</I> (L.) Merr fruit and <I>E. longifolia</I> roots may be responsible for the antimalarial activity. Taken together, our extraction conditions provided extracts containing novel active compounds that did not antagonize the inhibitory effects of the two widely used antimalarials. This finding could lend support to the future discovery of active antimalaria compounds of <I>Brucea javanica</I> (L.) Merr. and <I>Eurycoma longifolia</I> Jack as drugs for the treatment of malaria that could be employed as drug combinations in order to delay the onset of parasite drug resistance.