Shin, H. J. | bioRxiv Science

bioRxiv2021

Chitinase 3-like-1 is a Therapeutic Target That Mediates the Effects of Aging in COVID-19

COVID-19 is caused by the SARS-CoV-2 (SC2) virus and is more prevalent and severe in the elderly and patients with comorbid diseases (CM). Because chitinase 3-like-1 (CHI3L1) is induced during aging and CM, the relationships between CHI3L1 and SC2 were investigated. Here we demonstrate that CHI3L1 is a potent stimulator of the SC2 receptor ACE2 and viral spike protein priming proteases (SPP), that ACE2 and SPP are induced during aging and that anti-CHI3L1, kasugamycin and inhibitors of phosphorylation, abrogate these ACE2- and SPP-inductive events. Human studies also demonstrated that the levels of circulating CHI3L1 are increased in the elderly and patients with CM where they correlate with COVID-19 severity. These studies demonstrate that CHI3L1 is a potent stimulator of ACE2 and SPP; that this induction is a major mechanism contributing to the effects of aging during SC2 infection and that CHI3L1 coopts the CHI3L1 axis to augment SC2 infection. CHI3L1 plays a critical role in the pathogenesis of and is an attractive therapeutic target in COVID-19.

immunology↗

bioRxiv2019

Novel surface plasmon resonance biosensor that uses full-length Det7 phage tail protein for rapid and selective detection of Salmonella enterica serovar Typhimurium

We report a novel surface plasmon resonance (SPR) biosensor that uses the full-length Det7 phage tail protein (Det7T) to rapidly and selectively detect Salmonella enterica serovar Typhimurium. Det7T, which was obtained using recombinant protein expression and purification in Escherichia coli, demonstrated a size of [~]75 kDa upon SDS-PAGE and was homotrimeric in its native structure. Micro-agglutination and TEM data revealed that the protein specifically bound to the host, S. Typhimurium, but not to non-host E. coli K-12 cells. The observed protein agglutination occurred over a concentration range of 1.5[~]25 g.ml-1. The Det7T proteins were immobilized on gold-coated surfaces using amine-coupling to generate a novel Det7T-functionalized SPR biosensor, wherein the specific binding of these proteins with bacteria was detected by SPR. We observed rapid detection of ([~] 20 min) and typical binding kinetics with S. Typhimurium in the range of 5 x 104-5 x 107 CFU.ml-1, but not with E. coli at any tested concentration, indicating that the sensor exhibited recognition specificity. Similar binding was observed with 10% apple juice spiked with S. Typhimurium, suggesting that this strategy could be expanded for the rapid and selective monitoring of target microorganisms in the environment.

bioengineering↗