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Sub-structure-based screening and molecular docking studies of potential enteroviruses inhibitors

James SA, Yam WK

Comput Biol Chem, 2021 Jun;92:107499.
PMID: 33932782 DOI: 10.1016/j.compbiolchem.2021.107499

Rhinoviruses (RV), especially Human rhinovirus (HRVs) have been accepted as the most common cause for upper respiratory tract infections (URTIs). Pleconaril, a broad spectrum anti-rhinoviral compound, has been used as a drug of choice for URTIs for over a decade. Unfortunately, for various complications associated with this drug, it was rejected, and a replacement is highly desirable. In silico screening and prediction methods such as sub-structure search and molecular docking have been widely used to identify alternative compounds. In our study, we have utilised sub-structure search to narrow down our quest in finding relevant chemical compounds. Molecular docking studies were then used to study their binding interaction at the molecular level. Interestingly, we have identified 3 residues that is worth further investigation in upcoming molecular dynamics simulation systems of their contribution in stable interaction.
Fulltext A systematic bioinformatics approach for large-scale identification and characterization of host-pathogen shared sequences

James SA, Ong HS, Hari R, Khan AM

BMC Genomics, 2021 Sep 28;22(Suppl 3):700.
PMID: 34583643 DOI: 10.1186/s12864-021-07657-4

BACKGROUND: Biology has entered the era of big data with the advent of high-throughput omics technologies. Biological databases provide public access to petabytes of data and information facilitating knowledge discovery. Over the years, sequence data of pathogens has seen a large increase in the number of records, given the relatively small genome size and their important role as infectious and symbiotic agents. Humans are host to numerous pathogenic diseases, such as that by viruses, many of which are responsible for high mortality and morbidity. The interaction between pathogens and humans over the evolutionary history has resulted in sharing of sequences, with important biological and evolutionary implications.
RESULTS: This study describes a large-scale, systematic bioinformatics approach for identification and characterization of shared sequences between the host and pathogen. An application of the approach is demonstrated through identification and characterization of the Flaviviridae-human share-ome. A total of 2430 nonamers represented the Flaviviridae-human share-ome with 100% identity. Although the share-ome represented a small fraction of the repertoire of Flaviviridae (~ 0.12%) and human (~ 0.013%) non-redundant nonamers, the 2430 shared nonamers mapped to 16,946 Flaviviridae and 7506 human non-redundant protein sequences. The shared nonamer sequences mapped to 125 species of Flaviviridae, including several with unclassified genus. The majority (~ 68%) of the shared sequences mapped to Hepacivirus C species; West Nile, dengue and Zika viruses of the Flavivirus genus accounted for ~ 11%, ~ 7%, and ~ 3%, respectively, of the Flaviviridae protein sequences (16,946) mapped by the share-ome. Further characterization of the share-ome provided important structural-functional insights to Flaviviridae-human interactions.
CONCLUSION: Mapping of the host-pathogen share-ome has important implications for the design of vaccines and drugs, diagnostics, disease surveillance and the discovery of unknown, potential host-pathogen interactions. The generic workflow presented herein is potentially applicable to a variety of pathogens, such as of viral, bacterial or parasitic origin.
Fulltext Phylogenomics and the rise of the angiosperms

Zuntini AR, Carruthers T, Maurin O, Bailey PC, Leempoel K, Brewer GE, et al.

Nature, 2024 May;629(8013):843-850.
PMID: 38658746 DOI: 10.1038/s41586-024-07324-0

Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods1,2. A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome3,4. Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins5-7. However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes8. This 15-fold increase in genus-level sampling relative to comparable nuclear studies9 provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade.

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