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Biology subjects

Klug, E.

Publications and source records attributed to Klug, E..

2 recordsLinked to original sources

A novel chitinase-like family of candidate effectors unique to aphids

Molecular interactions between aphids and plants include delivery of salivary effector proteins into host cells, acting as virulence factors to suppress host immunity, or as avirulence functions triggering immune activation. However, understanding of virulence and avirulence mechanisms in aphid-plant systems is currently limited. Here, we report discovery of an effector candidate family that is unique to aphids. Using functional genomics data on divergent pea aphid (Acyrthosiphon pisum) genotypes and their F1 progeny, we filtered for differentially expressed saliva proteins that co-segregated with virulence or avirulence phenotypes. LOC100575698 (ACPISUM_029930), annotated as an uncharacterized protein, was the sole candidate effector for which RNA-Seq and saliva proteomics data showed significantly different expression both between avirulent and virulent parents and between their segregating F1 progeny, with this gene upregulated in avirulent genotypes. BLASTP searches revealed multiple divergent homologs only in genomes of the Aphidomorpha infra-order, suggesting a hitherto undefined ancient aphid-specific gene family. AlphaFold models indicate strong structural similarities but weak sequence homology to chitinases. Because the aphid-specific clade all lack canonical DxxDxDxE motifs for catalytic activity, we designate the proteins as a novel CHitinase-Like (CHL) family. Association of ACPISUM_029930 (ApCHL1) with avirulence was further supported by co-segregating SNPs and a genotype-specific alternatively spliced isoform. We hypothesise that CHL proteins may function similarly to phylogenetically unrelated chitin-binding fungal effectors that sequester chitin, also present in aphid stylets, potentially preventing defence activation through plant chitin receptors and/or blocking chitin degradation by host-secreted chitinases.

molecular biology↗

Discovery and in-vitro evaluation of potent SARS-CoV-2 entry inhibitors

SARS-CoV-2 infection initiates with the attachment of spike protein to the ACE2 receptor. While vaccines have been developed, no SARS-CoV-2 specific small molecule inhibitors have been approved. Herein, utilizing the crystal structure of the ACE2/Spike receptor binding domain (S-RBD) complex in computer-aided drug design (CADD) approach, we docked [~]8 million compounds within the pockets residing at S-RBD/ACE2 interface. Five best hits depending on the docking score, were selected and tested for their in vitro efficacy to block SARS-CoV-2 replication. Of these, two compounds (MU-UNMC-1 and MU-UNMC-2) blocked SARS-CoV-2 replication at sub-micromolar IC50 in human bronchial epithelial cells (UNCN1T) and Vero cells. Furthermore, MU-UNMC-2 was highly potent in blocking the virus entry by using pseudoviral particles expressing SARS-CoV-2 spike. Finally, we found that MU-UNMC-2 is highly synergistic with remdesivir (RDV), suggesting that minimal amounts are needed when used in combination with RDV, and has the potential to develop as a potential entry inhibitor for COVID-19.

molecular biology↗