Biology subjects

Liechti, N.

Publications and source records attributed to Liechti, N..

3 recordsLinked to original sources

bioRxiv2025

Genomic Evidence for a Novel Introduction and Intra-host Diversity of DENV-2 in Dar es Salaam, Tanzania

Dengue virus (DENV) poses a growing risk in Tanzania, yet its diversity in mosquitoes is poorly understood. Using Nanopore sequencing, we recovered full coding sequences from six DENV-2 positive mosquito pools collected in Dar es Salaam outside outbreak periods. Phylogenetic analysis placed the sequences in a distinct monophyletic clade within genotype II, separate from strains linked to Tanzanias 2014 outbreak. Instead, they clustered with Asian lineages, showing closest relatedness to DENV-2 from Kenya (2013) and India (2014), with divergence estimated around 2010. Variant profiling identified 212 low-frequency intra-host variants, largely nonsynonymous changes in NS3 and NS5. These results suggest an unrecognized introduction of genotype II now circulating silently in local mosquito populations. Our findings highlight the value of genomic surveillance in vectors for early detection of arboviral threats, even when human cases are absent.

genomics↗

bioRxiv2021

A beta-glucosidase of an insect herbivore determines both toxicity and deterrence of a dandelion defense metabolite

Gut enzymes can metabolize plant defense metabolites and thereby affect the growth and fitness of insect herbivores. Whether these enzymes also influence herbivore behavior and feeding preference is largely unknown. We studied the metabolization of taraxinic acid {beta}-D-glucopyranosyl ester (TA-G), a sesquiterpene lactone of the common dandelion (Taraxacum officinale) that deters its major root herbivore, the common cockchafer larva (Melolontha melolontha). We demonstrate that TA-G is rapidly deglycosylated and conjugated to glutathione in the insect gut. A broad-spectrum M. melolontha {beta}-glucosidase, Mm_bGlc17, is sufficient and necessary for TA-G deglycosylation. Using plants and insect RNA interference, we show that Mm_bGlc17 reduces TA-G toxicity. Furthermore, Mm_bGlc17 is required for the preference of M. melolontha larvae for TA-G deficient plants. Thus, herbivore metabolism modulates both the toxicity and deterrence of a plant defense metabolite. Our work illustrates the multifacteted roles of insect digestive enzymes as mediators of plant-herbivore interactions.

ecology↗

bioRxiv2021

Multi-specific DARPin(R) therapeutics demonstrate very high potency against mutated SARS-CoV-2 variants in vitro

SARS-CoV-2 has infected millions of people globally and continues to undergo evolution. Emerging variants can be partially resistant to vaccine induced immunity and therapeutic antibodies, emphasizing the urgent need for accessible, broad-spectrum therapeutics. Here, we report a comprehensive study of ensovibep, the first trispecific clinical DARPin candidate, that can simultaneously engage all three units of the spike protein trimer to potently inhibit ACE2 interaction, as revealed by structural analyses. The cooperative binding of the individual modules enables ensovibep to retain inhibitory potency against all frequent SARS-CoV-2 variants, including Omicron BA.1 and BA.2, as of February 2022. Moreover, viral passaging experiments show that ensovibep, when used as a single agent, can prevent development of escape mutations comparably to a cocktail of monoclonal antibodies (mAb). Finally, we demonstrate that the very high in vitro antiviral potency also translates into significant therapeutic protection and reduction of pathogenesis in Roborovski dwarf hamsters infected with either the SARS-CoV-2 wild-type or the Alpha variant. In this model, ensovibep prevents fatality and provides substantial protection equivalent to the standard of care mAb cocktail. These results support further clinical evaluation and indicate that ensovibep could be a valuable alternative to mAb cocktails and other treatments for COVID-19.

immunology↗