Viruses rapidly evolve to stay a step ahead of their hosts. Current in vitro evolution techniques can help us to minimize such a gap. We used an enhanced yeast display technique to affinity maturate the spike protein's receptor-binding domain (RBD) towards ACE2. This process led to the immediate isolation of prominent mutations among the SARS-CoV2 samples, e.g. S477N, E484K, and N501Y. Further in vitro evolution provided us with important mutations that might arise in the future and the 600-fold tighter binding RBD-62 molecule that can be used as a strong competitive inhibitor-resistant to mutations in viral RBD. Currently, the RBD-62 inhalation treatment efficacy is tested on primates in collaboration with NIH.
While working on the RBD-62 and inspired by the similarity between in vitro and real data, we perceive an important and so far underappreciated phenomenon. Everyone realized the striking similarity between α, β and γ variants, but the phenomenon goes far beyond this simple observation. We found at least 31 mutations evolving ≥3-times independently within separated lineages. These mutations cluster in three functional domains; the N-terminal domain, receptor-binding domain, and Furin cleavage site. Most concerning, SARS-CoV-2 lineages carry the heaviest burden of convergent residues, supporting their significant contribution to adaptive advantage and projecting continuous acquisition.

Viruses rapidly evolve to stay a step ahead of their hosts. Current _in vitro_ evolution techniques can help us to minimize such a gap. We used an enhanced yeast display technique to affinity maturate the spike protein's receptor-binding domain (RBD) towards ACE2. This process led to the immediate isolation of prominent mutations among the SARS-CoV2 samples, e.g. S477N, E484K, and N501Y. Further in vitro evolution provided us with important mutations that might arise in the future and the 600-fold tighter binding RBD-62 molecule that can be used as a strong competitive inhibitor-resistant to mutations in viral RBD. Currently, the RBD-62 inhalation treatment efficacy is tested on primates in collaboration with NIH.
While working on the RBD-62 and inspired by the similarity between _in vitro_ and real data, we perceive an important and so far underappreciated phenomenon. Everyone realized the striking similarity between α, β and γ variants, but the phenomenon goes far beyond this simple observation. We found at least 31 mutations evolving ≥3-times independently within separated lineages. These mutations cluster in three functional domains; the N-terminal domain, receptor-binding domain, and Furin cleavage site. Most concerning, SARS-CoV-2 lineages carry the heaviest burden of convergent residues, supporting their significant contribution to adaptive advantage and projecting continuous acquisition.

Mimicking SARS-Cov2 spike evolution results in a potent inhibitor of predicts future developments

Exploring the intricacies of host-pathogen communication is vital in order to understand why
some microbes persist within a host, while others are effectively cleared. As such,
host-pathogen communication is an urgent area of research underpinning human health
and disease, especially given the emerging concerns of antibiotic resistance.
Understanding host-pathogen pathways requires intricate knowledge in the fields of both
microbiology and immunology.

Living in a world of specialists, where scientists sometimes invest their whole career
studying one organism, a specific pathway or a protein, multidisciplinary discussions of
host-pathogen interactions are highly needed. This international conference will provide
such a forum for scientific exchange at the highest level, between scientists from different
research areas related to host-pathogen interactions, with the aim to trigger fruitful
collaborations addressing the urgent questions in the field.

This meeting has an additional special focus of bringing researchers from Ireland, Denmark
and Israel together to learn about cutting edge biology and form new collaborations.
Thus, the conference will be a showcase for the exciting and original research emanating
from these three small but innovative countries.

Host-Pathogen Communication (HPC) 2021

Awards & close

Initiation and Regulation of Innate Immunity

Plasmacytoid dendritic cells sense SARS-CoV-2 through TLR2-IL6 and TLR7-INFα pathways that protect epithelial cells from infection

Mouse models carrying patient-derived mutations in IRF3 and TBK1 enable mechanistic characterization of herpes simplex encephalitis

A diamidobenzimidazole STING agonist protects against SARS-CoV-2 infection

Coordinating immune-defence functions of MLKL: endosomal targeting of MLKL by site specific ubiquitination facilitates lysosomal destruction of intracellular pathogenes