Farnesyltransferase inhibitor lonafarnib suppresses respiratory syncytial virus infection by blocking conformational change of fusion glycoprotein

Respiratory syncytial virus(RSV)is the major cause of bronchiolitis and pneumonia in young children and the elderly.There are currently no approved RSV-specific therapeutic small molecules available.Using high-throughput antiviral screening,we identified an oral drug,the prenylation inhibitor lonafarnib,which showed potent inhibition of the RSV fusion process.Lonafarnib exhibited antiviral activity against both the RSV A and B genotypes and showed low cytotoxicity in HEp-2 and human primary bronchial epithelial cells(HBEC).Time-of-addition and pseudovirus assays demonstrated that lonafarnib inhibits RSV entry,but has farnesyltransferase-independent antiviral efficacy.Cryo-electron microscopy revealed that lonafarnib binds to a triple-symmetric pocket within the central cavity of the RSV F metastable pre-fusion conformation.Mutants at the RSV F sites interacting with lonafarnib showed resistance to lonafarnib but remained fully sensitive to the neutralizing monoclonal antibody palivizumab.Furthermore,lonafarnib dose-dependently reduced the replication of RSV in BALB/c mice.Collectively,lonafarnib could be a potential fusion inhibitor for RSV infection.

Micro-scale opto-thermo-mechanical actuation in the dry adhesive regime

Realizing optical manipulation of microscopic objects is crucial in the research fields of life science,condensed matter physics,and physical chemistry.In non-liquid environments,this task is commonly regarded as difficult due to strong adhesive surface force(~µN)attached to solid interfaces that makes tiny optical driven force(~pN)insignificant.Here,by recognizing the microscopic interaction mechanism between friction force—the parallel component of surface force on a contact surface—and thermoelastic waves induced by pulsed optical absorption,we establish a general principle enabling the actuation of micro-objects on dry frictional surfaces based on the opto-thermo-mechanical effects.Theoretically,we predict that nanosecond pulsed optical absorption with mW-scale peak power is sufficient to tameµN-scale friction force.Experimentally,we demonstrate the two-dimensional spiral motion of gold plates on micro-fibers driven by nanosecond laser pulses,and reveal the rules of motion control.Our results pave the way for the future development of micro-scale actuators in non-liquid environments.

‘Plug-and-play’ plasmonic metafibers for ultrafast fibre lasers

Metafibers expand the functionalities of conventional optical fibres to unprecedented nanoscale light manipulations by integrating metasurfaces on the fibre tips,becoming an emerging light-coupling platform for both the nanoscience and fibre optics communities.Current metafibers remain proof-of-concept demonstrations that mostly explore isolated bare fibres owing to the lack of standard interfaces with universal fibre networks.Here,we develop methodologies for fabricating well-defined plasmonic metasurfaces directly on the end facets of commercial single-mode fibre jumpers using standard planar technologies and provide the first demonstration of their practical applications in the nonlinear plasmonic regime.Featuring plug-and-play connections with fibre circuitry and arbitrary metasurface landscapes,the metafibers with tunable plasmonic resonances are implemented into fibre laser cavities,yielding all-fibre sub-picosecond(minimum 513 fs)soliton mode locked lasers at optical wavelengths of 1.5μm and 2μm,demonstrating their unusual polarimetric nonlinear transfer functions and superior saturation absorption responses.The nanofabrication process flow is compatible with existing cleanroom technologies,offering metafibers an avenue to become a regular member of functionalised fibre components.This work paves the way toward the next generation of ultrafast lasers,optical frequency combs,and ultracompact‘all-in-fibre’optical systems.

Controllable generation of large-scale highly regular gratings on Si films

The application of femtosecond laser-induced periodic surface texturing has significant potential in medicine,optics,tribology,and biology,among other areas.However,when irradiated by a large intense laser spot,the periodic structures usually exhibit an uncontrollable regularity,forming bifurcated patterns,thus limiting their widespread application.Irregularity originates from numerous independent branching seeds.The usual solution to this problem is to utilize the quasi-direct laser writing technique,that is,by limiting the laser beam size(diameter of<10 wavelengths)and scanning the beam or samples using 2D translation stages.Herein,we demonstrate an optical localization-induced nonlinear competition mechanism to solve this problem,which occurs at a fluence nearly one order of magnitude below the ablation threshold.Owing to the low intrinsic absorption of silicon and ultralow applied fluence,this mechanism ensures the self-selection of a single seed to initiate an array of bifurcated-free gratings under stationary irradiation with a large laser spot(diameter>100 wavelengths).Surprisingly,some unconventional complex patterns,such as radial,annular,and spiral gratings,can also be easily produced by structured light fields with unprecedented regularity.Their diameters reach up to>500μm.Moreover,we can artificially control the initial seeding structure to further improve the regularity of the gratings,defined by dispersion in the ripple orientation angle in their 2D Fourier transform.As a result,the regularity in our experiments produced by a large laser spot is even higher than that scanned by a tiny beam.Controllable and highly regular ripples are beneficial to the structural coloring effects because they arise from the light diffraction by subwavelength gratings.

Enhanced nonlinearity for filamentation in gold-nanoparticle-doped water

We report a universal approach based on the surface plasmon resonances(SPRs) attained in filamentation in water doped with gold nanoparticles for enhancing the nonlinear refractive index. The filament-induced supercontinuum spectrum in water overlaps with SPRs of gold nanospheres, which further leads to a modification on the Kerr nonlinear refractive index. In our experiment, the measured nonlinear refractive index(n_2) in water doped with gold nanoparticles increases by six times, as compared with that in pure water. Such enhancement may be useful for filament-induced nonlinear applications with modest incident intensity.

A core epitope targeting antibody of SARS-CoV-2

Dear Editor,Tremendous efforts have been made globally to develop therapeutics and prophylactics against severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)which has caused thousands of millions of infections and deaths worldwide.A series of potent neutralizing antibodies with defined epitopes targeting RBD have been recently identified with different strategies.However,being an RNA virus,the instability of the SARS-CoV-2 genome results in numerous S-protein variants with altered viral phenotypes.