A major challenge to end the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is to develop a broadly protective vaccine that elicits long-term immunity. As the key immunogen, the viral surface spike (S) protein is frequently mutated, and conserved epitopes are shielded by glycans. Here, we revealed that S protein glycosylation has site-differential effects on viral infectivity. We found that S protein generated by lung epithelial cells has glycoforms associated with increased infectivity. Compared to the fully glycosylated S protein, immunization of S protein with N-glycans trimmed to the mono-GlcNAc–decorated state (S _MG ) elicited stronger immune responses and better protection for human angiotensin-converting enzyme 2 (hACE2) transgenic mice against variants of concern (VOCs). In addition, a broadly neutralizing monoclonal antibody was identified from S _MG -immunized mice that could neutralize wild-type SARS-CoV-2 and VOCs with subpicomolar potency. Together, these results demonstrate that removal of glycan shields to better expose the conserved sequences has the potential to be an effective and simple approach for developing a broadly protective SARS-CoV-2 vaccine.

The influenza virus hemagglutinin (HA) and coronavirus spike (S) protein mediate virus entry. HA and S proteins are heavily glycosylated, making them potential targets for carbohydrate binding agents such as lectins. Here, we show that the lectin FRIL, isolated from hyacinth beans (Lablab purpureus), has anti-influenza and anti-SARS-CoV-2 activity. FRIL can neutralize 11 representative human and avian influenza strains at low nanomolar concentrations, and intranasal administration of FRIL is protective against lethal H1N1 infection in mice. FRIL binds preferentially to complex-type N-glycans and neutralizes viruses that possess complex-type N-glycans on their envelopes. As a homotetramer, FRIL is capable of aggregating influenza particles through multivalent binding and trapping influenza virions in cytoplasmic late endosomes, preventing their nuclear entry. Remarkably, FRIL also effectively neutralizes SARS-CoV-2, preventing viral protein production and cytopathic effect in host cells. These findings suggest a potential application of FRIL for the prevention and/or treatment of influenza and COVID-19.

Biofilm formation is one of the main causes of increased antibiotic resistance in Acinetobacter baumannii infections. Bacteriophages and their derivatives, such as tail proteins with depolymerase activity, have shown considerable potential as antibacterial or antivirulence agents against bacterial infections. Here, we gained insights into the activity of a capsular polysaccharide (CPS) depolymerase, derived from the tailspike protein (TSP) of φAB6 phage, to degrade A. baumannii biofilm in vitro. Recombinant TSP showed enzymatic activity and was able to significantly inhibit biofilm formation and degrade formed biofilms; as low as 0.78 ng, the inhibition zone can still be formed on the bacterial lawn. Additionally, TSP inhibited the colonization of A. baumannii on the surface of Foley catheter sections, indicating that it can be used to prevent the adhesion of A. baumannii to medical device surfaces. Transmission and scanning electron microscopy demonstrated membrane leakage of bacterial cells treated with TSP, resulting in cell death. The therapeutic effect of TSP in zebrafish was also evaluated and the results showed that the survival rate was significantly improved (80%) compared with that of the untreated control group (10%). Altogether, we show that TSP derived from φAB6 is expected to become a new antibiotic against multi-drug resistant A. baumannii and a biocontrol agent that prevents the formation of biofilms on medical devices.

Because oral transmission of SARS-CoV-2 is 3–5 orders of magnitude higher than nasal transmission, we investigated debulking of oral viruses using viral trap proteins (CTB-ACE2, FRIL) expressed in plant cells, delivered through the chewing gum. In omicron nasopharyngeal (NP) samples, the microbubble count (based on N-antigen) was significantly reduced by 20 μg of FRIL (p < 0.0001) and 0.925 μg of CTB-ACE2 (p = 0.0001). Among 20 delta or omicron NP samples, 17 had virus load reduced below the detection level of spike protein in the RAPID assay, after incubation with the CTB-ACE2 gum powder. A dose-dependent 50% plaque reduction with 50–100 ng FRIL or 600–800 μg FRIL gum against Influenza strains H1N1, H3N2, and Coronavirus HCoV-OC43 was observed with both purified FRIL, lablab bean powder or gum. In electron micrographs, large/densely packed clumps of overlapping influenza particles and FRIL protein were observed. Chewing simulator studies revealed that CTB-ACE2 release was time/dose-dependent and release was linear up to 20 min chewing. Phase I/II placebo-controlled, double-blinded clinical trial (IND 154897) is in progress to evaluate viral load in saliva before or after chewing CTB-ACE2/placebo gum. Collectively, this study advances the concept of chewing gum to deliver proteins to debulk oral viruses and decrease infection/transmission.

Background Persicaria hydropiper Linn. (Family: Polygonaceae), it grows in damp places and the bank of rivers, canals, lakes, and roadsides of Bangladesh. The leaves of the plant used in traditional medicine to treat insomnia, depression, and neurodegenerative diseases. The objective of this study is to investigate the sedative and anxiolytic activities of the methanol extract of leaves of Persicaria hydropiper (MEPH). Methods The sedative effect of the P. hydropiper at the doses of 50, 200, 350, and 500 mg/kg evaluated using the open field, hole cross, rota-rod and thiopental sodium-induced sleeping time test in mice. The anxiolytic activity evaluated using the elevated-plus maze, light-dark box, hole-board and marble-burying test. Sedative and anxiolytic activities compared to diazepam, a positive control. The acute toxicity test also assessed. Results The neuropharmacological activity of both open field and hole cross tests significant (p < 0.001) decrease the number of (square and hole) crosses by mice compare to control group. The rota-rod test to evaluate the motor coordination or muscle relaxant significantly (p < 0.001) increases the number of falling whereas decrease performance time from the rotating rod. In thiopental sodium-induced sleeping test, MEPH causes a decrease in the sleep latency time and significantly (p < 0.001) increase the duration of sleeping time. In the elevated plus-maze test, the different parameters (the time spent and the number of entries in open arms; the time spent and the number of entries in close arms) observed. Treatment with MEPH significant (p < 0.001) increase the time spent and the number of entries in open arms comparable to control group. In respect of the light-dark box test, several (latency times, the number of transitions, the time spent in the light and dark compartment) parameters also observed. Mice treated with MEPH significant (p < 0.001) increase the time spent in the light compartment compared to control group. The hole-board tests, MEPH significant (p < 0.001) decrease the number of head dips, as well as the number of marbles burying, was significant (p < 0.001) decrease in the marble-burying test showing anxiolytic activity. Conclusion The results indicate that MEPH has sedative and anxiolytic activities, supporting its uses in traditional medicine. Further studies of the isolation of the active components of P. hydropiper and its mechanism of action study strongly recommended before the application in human.