A three-compound dengue treatment; plus reversing antibiotic resistance, AbCellera-Lilly, reducing cholesterol with CRISPR and COVID cash for Sherlock

Hindering dengue by combining host- and virus-targeted drugs
In a Cell Chemical Biology article, Stanford University scientists combined two host-targeted compounds with a virus-targeted compound to yield potent dengue treatment. A DHODH inhibitor tool compound, which blocks de novo pyrimidine synthesis, plus a cyclopentenyl uracil analog that inhibits pyrimidine salvage suppressed viral replication in cell culture compared with either compound alone. The two molecules plus a cytidine analog, which blocks dengue virus RNA-dependent RNA polymerase, led to more potent viral inhibition than the antiviral alone or any two-component combination.

Resensitizing drug-resistant bacteria
A China Agricultural University team have shown in Nature Microbiology that a linear 11-residue peptide dubbed SLAP-S25 could serve as an adjuvant for multiple antibiotics to treat infections by various multidrug resistant Gram-negative bacterial species. SLAP-S25, which interacted with lipids in inner and outer bacterial membranes to disrupt membrane integrity, boosted the potency of the last-resort antibiotic colistin against pathogens including E. coli, Acinetobacter baumannii and Salmonella enteritidis. The peptide also enhanced the activity of antibiotics including vancomycin, tetracycline and rifampicin against an multidrug resistant E. coli strain. In a peritonitis-sepsis mouse model, colistin plus SLAP-S25 reduced E. coli loads in heart, liver, spleen, kidney and lung tissue and increased survival...