Viral afterlife: SARS-CoV-2 as a reservoir of immunomimetic peptides that reassemble into proinflammatory supramolecular complexes

It is unclear how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to the strong but ineffective inflammatory response that characterizes severe Coronavirus disease 2019 (COVID-19), with amplified immune activation in diverse cell types, including cells without angiotensin-converting enzyme 2 receptors necessary for infection. Proteolytic degradation of SARS-CoV-2 virions is a milestone in host viral clearance, but the impact of remnant viral peptide fragments from high viral loads is not known. Here, we examine the inflammatory capacity of fragmented viral components from the perspective of supramolecular self-organization in the infected host environment. Interestingly, a machine learning analysis to SARS-CoV-2 proteome reveals sequence motifs that mimic host antimicrobial peptides (xenoAMPs), especially highly cationic human cathelicidin LL-37 capable of augmenting inflammation. Such xenoAMPs are strongly enriched in SARS-CoV-2 relative to low-pathogenicity coronaviruses. Moreover, xenoAMPs from SARS-CoV-2 but not low-pathogenicity homologs assemble double-stranded RNA (dsRNA) into nanocrystalline complexes with lattice constants commensurate with the steric size of Toll-like receptor (TLR)-3 and therefore capable of multivalent binding. Such complexes amplify cytokine secretion in diverse uninfected cell types in culture (epithelial cells, endothelial cells, keratinocytes, monocytes, and macrophages), similar to cathelicidin’s role in rheumatoid arthritis and lupus. The induced transcriptome matches well with the global gene expression pattern in COVID-19, despite using <0.3% of the viral proteome. Delivery of these complexes to uninfected mice boosts plasma interleukin-6 and CXCL1 levels as observed in COVID-19 patients

Óleo de citronela no controle do carrapato de bovinos Citronella oil on the control of catle ticks

O objetivo deste estudo foi avaliar o efeito in vivo e in vitro do óleo de citronela (Cymbopogon nardus (L.) Rendle) no carrapato de bovinos (Boophilus microplus). O óleo foi obtido de folhas frescas pelo processo de destilação e o rendimento foi de 0,7%. Para as experimentações in vitro foram usadas sete (0; 0,5; 1,0; 10,0; 25,0; 50,0; 100,0%) e nove (0,1; 0,25; 0,5; 1,0; 2,0; 10,0; 25,0; 50,0; 100%) concentrações de óleo de citronela, sendo testadas em fêmeas ingurgitadas. A eficácia observada foi de 0; 44,2; 92,1; 85,6; 87,8; 87,0; 88,9 e de 0,7; 2,8; 51,6; 79,3; 81,0; 87,1; 86,7; 89,5%, respectivamente. Os resultados sugerem que o óleo de citronela pode ser usado no controle do carrapato bovino.<br>This research was aimed at evaluating in vitro and in vivo effects of citronella (Cymbopogon nardus (L.) Rendle) oil on catle ticks. The volatile oil was obtained from de fresh leaves of citronella grass by steam destilation and the yelds was 0.7%. Seven (0; 0.5; 1.0; 10.0; 25.0; 50.0; 100.0%) and nine (0.1; 0.25; 0.5; 1.0; 2.0; 10.0; 25.0; 50.0; 100.0%) concentrations of citonella oil were used on in vitro trials with engorged female ticks. The efficacy control ticks was 0; 44.2; 92.1; 85.6; 87.8; 87.0; 88.9 and 0; 0.7; 2.8; 51.6; 79.3; 81.0; 87.1; 86.7 89.5 %, respectively. These sugest that the citronella oil can be practical used for controlling of catle ticks