Transaminase-catalysis to produce trans-4-substituted cyclohexane-1-amines including a key intermediate towards cariprazine.

Cariprazine-the only single antipsychotic drug in the market which can handle all symptoms of bipolar I disorder-involves trans-4-substituted cyclohexane-1-amine as a key structural element. In this work, production of trans-4-substituted cyclohexane-1-amines was investigated applying transaminases either in diastereotope selective amination starting from the corresponding ketone or in diastereomer selective deamination of their diasteromeric mixtures. Transaminases were identified enabling the conversion of the cis-diastereomer of four selected cis/trans-amines with different 4-substituents to the corresponding ketones. In the continuous-flow experiments aiming the cis diastereomer conversion to ketone, highly diastereopure trans-amine could be produced (de > 99%). The yield of pure trans-isomers exceeding their original amount in the starting mixture could be explained by dynamic isomerization through ketone intermediates. The single transaminase-catalyzed process-exploiting the cis-diastereomer selectivity of the deamination and thermodynamic control favoring the trans-amines due to reversibility of the steps-allows enhancement of the productivity of industrial cariprazine synthesis.

Discovery and Characterization of RGH-122, a Potent, Selective, and Orally Bioavailable V1a Receptor Antagonist.

The V1a receptor is a major contributor in mediating the social and emotional effects of arginine-vasopressin (AVP); therefore it represents a promising target in the treatment of several neuropsychiatric conditions. The aim of this research was to design and synthesize novel and selective V1a antagonists with improved in vitro and in vivo profiles. Through optimization and detailed SAR studies, we developed low nanomolar antagonists, and further characterizations led to the discovery of the clinical candidate compound 43 (RGH-122). The CNS activity of the compound was determined in a 3-chamber social preference test of autism in which RGH-122 successfully enhanced social preference with the lowest effective dose of 1.5 mg/kg.

Raman Spectroscopy Unfolds the Fate and Transformation of SWCNTs after Abrasive Wear of Epoxy Floor Coatings.

Nanomaterials are integrated within consumer products to enhance specific properties of interest. Their release throughout the lifecycle of nano-enabled products raises concerns; specifically, mechanical strains can lead to the generation of fragmented materials containing nanomaterials. We investigated the potential release of single-walled carbon nanotubes (SWCNTs-brand TUBALL™) from epoxy composite materials. A pin-on-disk-type tribometer was used for the accelerated mechanical aging of the nanocomposites. A pristine nanocomposite material, abraded material and debris obtained from the abrasion in the tribometer were analyzed by Raman spectroscopy. The airborne-produced particles were captured using particle collectors. Stat Peel's Identifier C2 system was used to monitor the SWCNT content of respirable particles produced during the abrasion test. The SWCNT amounts found were below the LoQ. The Raman spectra conducted on the Stat Peel filters helped identify the presence of free SWCNTs released from the epoxy matrix, although they were notably scarce. Raman spectroscopy has been proved to be a crucial technique for the identification, characterization and assessment of structural changes and degradation in SWCNTs that occurred during the abrasion experiments.

Oral Orexin Receptor 2 Agonist in Narcolepsy Type 1.

BACKGROUND: Narcolepsy type 1 is caused by severe loss or lack of brain orexin neuropeptides. METHODS: We conducted a phase 2, randomized, placebo-controlled trial of TAK-994, an oral orexin receptor 2-selective agonist, in patients with narcolepsy type 1. Patients with confirmed narcolepsy type 1 according to clinical criteria were randomly assigned to receive twice-daily oral TAK-994 (30 mg, 90 mg, or 180 mg) or placebo. The primary end point was the mean change from baseline to week 8 in average sleep latency (the time it takes to fall asleep) on the Maintenance of Wakefulness Test (range, 0 to 40 minutes; normal ability to stay awake, ≥20 minutes). Secondary end points included the change in the Epworth Sleepiness Scale (ESS) score (range, 0 to 24, with higher scores indicating greater daytime sleepiness; normal, <10) and the weekly cataplexy rate. RESULTS: Of the 73 patients, 17 received TAK-994 at a dose of 30 mg twice daily, 20 received 90 mg twice daily, 19 received 180 mg twice daily, and 17 received placebo. The phase 2 trial and an extension trial were terminated early owing to hepatic adverse events. Primary end-point data were available for 41 patients (56%); the main reason for missing data was early trial termination. Least-squares mean changes to week 8 in average sleep latency on the MWT were 23.9 minutes in the 30-mg group, 27.4 minutes in the 90-mg group, 32.6 minutes in the 180-mg group, and -2.5 minutes in the placebo group (difference vs. placebo, 26.4 minutes in the 30-mg group, 29.9 minutes in the 90-mg group, and 35.0 minutes the 180-mg group; P<0.001 for all comparisons). Least-squares mean changes to week 8 in the ESS score were -12.2 in the 30-mg group, -13.5 in the 90-mg group, -15.1 in the 180-mg group, and -2.1 in the placebo group (difference vs. placebo, -10.1 in the 30-mg group, -11.4 in the 90-mg group, and -13.0 in the 180-mg group). Weekly incidences of cataplexy at week 8 were 0.27 in the 30-mg group, 1.14 in the 90-mg group, 0.88 in the 180-mg group, and 5.83 in the placebo group (rate ratio vs. placebo, 0.05 in the 30-mg group, 0.20 in the 90-mg group, and 0.15 in the 180-mg group). A total of 44 of 56 patients (79%) receiving TAK-994 had adverse events, most commonly urinary urgency or frequency. Clinically important elevations in liver-enzyme levels occurred in 5 patients, and drug-induced liver injury meeting Hy's law criteria occurred in 3 patients. CONCLUSIONS: In a phase 2 trial involving patients with narcolepsy type 1, an orexin receptor 2 agonist resulted in greater improvements on measures of sleepiness and cataplexy than placebo over a period of 8 weeks but was associated with hepatotoxic effects. (Funded by Takeda Development Center Americas; TAK-994-1501 and TAK-994-1504 ClinicalTrials.gov numbers, NCT04096560 and NCT04820842.).

Fully Symmetric Cyclodextrin Polycarboxylates: How to Determine Reliable Protonation Constants from NMR Titration Data.

Acid-base properties of cyclodextrins (CDs), persubstituted at C-6 by 3-mercaptopropionic acid, sualphadex (Suα-CD), subetadex (Suß-CD) and sugammadex (Suγ-CD, the antidote of neuromuscular blocking steroids) were studied by 1H NMR-pH titrations. For each CD, the severe overlap in protonation steps prevented the calculation of macroscopic pKa values using the standard data fitting model. Considering the full symmetry of polycarboxylate structures, we reduced the number of unknown NMR parameters in the "Q-fitting" or the novel "equidistant macroscopic" evaluation approaches. These models already provided pKa values, but some of them proved to be physically unrealistic, deceptively suggesting cooperativity in carboxylate protonations. The latter problem could be circumvented by adapting the microscopic site-binding (cluster expansion) model by Borkovec, which applies pairwise interactivity parameters to quantify the mutual basicity-decreasing effect of carboxylate protonations. Surprisingly, only a single averaged interactivity parameter could be calculated reliably besides the carboxylate 'core' microconstant for each CD derivative. The speciation of protonation isomers hence could not be resolved, but the optimized microscopic basicity parameters could be converted to the following sets of macroscopic pKa values: 3.84, 4.35, 4.81, 5.31, 5.78, 6.28 for Suα-CD; 3.82, 4.31, 4.73, 5.18, 5.64, 6.06, 6.54 for Suß-CD and 3.83, 4.28, 4.65, 5.03, 5.43, 5.81, 6.18, 6.64 for Suγ-CD. The pH-dependent charge of these compounds can now be accurately calculated, in support of designing new analytical methods to exploit their charge-dependent molecular recognition such as in cyclodextrin-aided chiral capillary electrophoresis.

Sulfobutylation of Beta-Cyclodextrin Enhances the Complex Formation with Mitragynine: An NMR and Chiroptical Study.

Mitragynine (MTR), the main indole alkaloid of the well-known plant kratom (Mitragyna speciosa), is one of the most studied natural products nowadays, due to its remarkable biological effects. It is a partial agonist on the opioid receptors, and as such relieves pain without the well-known side-effects of the opioids applied in the clinical practice. MTR and its derivatives therefore became novel candidates for drug development. The poor aqueous solubility and low bioavailability of drugs are often improved by cyclodextrins (CyDs) as excipients through host-guest type complex formation. Among the wide variety of CyDs, sulfobutylether-beta-cyclodextrin (SBEßCyD) is frequently used and official in the European and U.S. Pharmacopoeia. Herein, the host-guest complexation of MTR with ßCyD and SBEßCyD was studied using chiroptical and NMR spectroscopy. It was found by NMR measurements that MTR forms a rather weak (logß11 = 0.8) 1:1 host-guest complex with ßCyD, while the co-existence of the 2MTR∙SBEßCyD and MTR∙SBEßCyD species was deducted from 1H NMR titrations in the millimolar MTR concentration range. Sulfobutylation of ßCyD significantly enhanced the affinity towards MTR. The structure of the formed inclusion complex was extensively studied by circular dichroism spectroscopy and 2D ROESY NMR. The insertion of the indole moiety was confirmed by both techniques.

Synthesis and Characterization of New V1A Antagonist Compounds: The Separation of Four Atropisomeric Stereoisomers.

A new class of selective vasopressin receptor 1A (V1A) antagonists was identified, where "methyl-scan" was performed around the benzene ring of the 5-hydroxy-triazolobenzazepine core. This led to the synthesis of two 10-methyl derivatives, each possessing a chiral axis and a stereogenic center. The four atropisomeric stereoisomers (involving two enantiomer pairs and atropisomeric diastereomers) could be successfully isolated and spectroscopically characterized. According to the in vitro pharmacological profiles of the compounds, the human V1A receptor has a strong preference toward the isomers having an aR axial chirality, the most active isomer being the aR,5S isomer. Furthermore, the structure-activity relationships obtained for the isomers and for the newly synthesized analogues could be tentatively explained by an in silico study.

Excited-state symmetry breaking in 9,10-dicyanoanthracene-based quadrupolar molecules: the effect of donor-acceptor branch length.

Excited-state symmetry breaking is investigated in a series of symmetric 9,10-dicyanoanthracenes linked to electron-donating groups on the 2 and 6 positions via different spacers, allowing for a tuning of the length of the donor-acceptor branches. The excited-state properties of these compounds are compared with their dipolar single-branch analogues. The changes in electronic structure upon their optical excitation are monitored by transient electronic spectroscopy in the visible and near-infrared regions as well as by transient vibrational spectroscopy in the mid-infrared. Our results reveal that, with the shortest branches, electronic excitation remains distributed almost symmetrically over the molecule even in polar environments. Upon increasing the donor-acceptor distance, excitation becomes unevenly distributed and, with the longest one, it fully localises on one branch in polar solvents. The influence of the branch length on the propensity of quadrupolar dyes to undergo excited-state symmetry breaking is rationalised in terms of the balance between interbranch coupling and solvation energy.

Excited-State Symmetry Breaking and the Laporte Rule.

Excited-state symmetry breaking (ES-SB) is common to a large number of multibranched electron donor-acceptor (DA) molecules in polar environments. During this process, the electronic excitation, originally evenly distributed over the molecule, localizes, at least partially, on one branch. Due to the absence of an unambiguous spectroscopic signature in the UV-vis region, electronic transient absorption (TA) has not been the method of choice for real-time observation of this phenomenon. Herein, we demonstrate that the Laporte rule, which states that one-photon transitions conserving parity are forbidden in centrosymmetric molecules, provides such clear signature of ES-SB in electronic TA spectroscopy. Using a dicyanoanthracene-based D-A-D dye, we show that transitions from the S1 state of this molecule, which are initially Laporte forbidden, become allowed upon ES-SB. This leads to the rise of new TA bands, whose intensity provides a direct measure of the extent of asymmetry in the excited state.

Structural characterization of fondaparinux interaction with per-6-amino-beta-cyclodextrin: An NMR and MS study.

The highly anionic synthetic pentasaccharide fondaparinux (FDPX) - representing the antithrombin binding sequence of heparin - is in clinical use as a potent anticoagulant. Contrary to the unfractionated heparin, FDPX lacks potent antidote completely reversing its anticoagulant activity, therefore it is of great importance to identify new structures exhibiting strong intermolecular interactions towards FDPX. The polycationic heptakis(6-amino-6-deoxy)-beta-cyclodextrin (NH2-ß-CD) can serve as an excellent model compound to mimic these interactions between the oppositely charged oligosaccharides. Herein, extensive NMR spectroscopic and nano-electrospray ionization mass spectrometric (nESI-MS) studies were conducted to understand the molecular-level interactions in the FDPX - NH2-ß-CD systems. NMR experiments were performed at pD 7.4 and 2.0. Job's method of continuous variation and 1H NMR titration experiments suggested the formation of FDPX∙NH2-ß-CD complex at pD 7.4, while the presence of multiple complexes was assumed at pD 2.0. Stability constants were determined by separate 1H NMR titrations, yielding log ß11=3.65 ± 0.02 at pD 7.4, while log ß11 ≥ 4.9 value suggested a high-affinity system at pD 2.0. 2D NOESY NMR studies indicated spatial proximities between the anomeric resonance α-l-iduronic acid residue and the cyclodextrin's methylene unit in the proximity of the cationic amino function. Acidic degradation of FDPX was investigated by NMR and MS for the first time in detail confirming that desulfation occurs involving one to two sulfate moieties. The desulfation of FDPX was inhibited by the cationic cyclodextrin in the case of equimolar ratio at pD 2.0. This is the first report on the stabilizing effect of cyclodextrin complexation on heparin degradation.

Discovery of New Heterocyclic Ring Systems as Novel and Potent V1A Receptor Antagonists.

Autism spectrum disorder is a neurodevelopmental disease with increasing occurrence. Recent studies focus on the development of novel V1A receptor antagonists which can influence the core symptoms of autism through the AVP pathway. In this study, we describe the synthesis of new heterocyclic ring systems. These are a novel class of brain-penetrating V1A antagonists with improved metabolic stability and in vivo potency. The efficacy of the compounds was strongly influenced by the position of the chlorine atom, suggesting halogen bond formation between the ligands and the V1A receptor.

Change of Quadrupole Moment upon Excitation and Symmetry Breaking in Multibranched Donor-Acceptor Dyes.

Upon photoexcitation, a majority of quadrupolar dyes, developed for large two-photon absorption, undergo excited-state symmetry breaking (ES-SB) and behave as dipolar molecules. We investigate how the change of quadrupole moment upon S1 ←S0 excitation, ΔQ, influences the propensity of a dye to undergo ES-SB using a series of molecules with a A-π-D-π-A motif where D is the exceptionally electron-rich pyrrolo[3,2-b]pyrrole and A are accepting groups. Tuning of ΔQ is achieved by appending a secondary acceptor group, A', on both sides of the D core and ES-SB is monitored using a combination of time-resolved IR and broadband fluorescence spectroscopy. The results reveal a clear correlation between ΔQ and the tendency to undergo ES-SB. When A is a stronger acceptor than A', ES-SB occurs already in non-dipolar but quadrupolar solvents. When A and A' are identical, ES-SB is only partial even in highly dipolar solvents. When A is a weaker acceptor than A', the orientation of ΔQ changes, ES-SB is observed in dipolar solvents only and involves major redistribution of the excitation over the D-π-A and D-A' branches of the dye.

Qualitative and Quantitative Phytochemical Analysis of Ononis Hairy Root Cultures.

Hairy root cultures are genetically and biochemically stable, and they regularly possess the same or better biosynthetic capabilities for specialized (secondary) metabolite production compared to the intact plant. Ononis species are well-known herbal remedies in ethnopharmacology and rich sources of isoflavonoids. Besides isoflavones, less prevalent isoflavones and pterocarpans with valuable biological effects can be found in Ononis species as well. As these plants are only collected but not cultivated, biotechnological methods could play a role in the larger-scale extraction of Ononis isoflavonoids. Regarding this information, we aimed to establish Ononis spinosa and Ononis arvensis hairy root cultures (HRCs) and analyze the isoflavonoid profile of hairy root cultures qualitatively and quantitatively, in order to define their capacity to produce biologically valuable isoflavonoids. During the qualitative description, beside isoflavonoids, two new phenolic lactones, namely, bulatlactone 2″-O-ß-D-glucoside and ononilactone, were isolated, and their structures were characterized for the first time. Altogether, 29 compounds were identified by the means of UPLC-Orbitrap-MS/MS. Based on UHPLC-UV-DAD measurements, the isoflavonoid spectrum of the Ononis HRCs differed markedly from wild-grown samples, as they produce a limited range of the scaffolds. The most abundant compounds in the HRCs were medicarpin glucoside and sativanone glucoside. The overall isoflavonoid production of the cultures was comparable to wild-grown O. arvensis and approximately twice as high as in wild-grown O. spinosa samples. As the overall content of wild-grown samples include more isoflavonoid derivatives, the HRCs contain structurally less divergent isoflavonoids but in higher quantity.

Long-term use of pitolisant to treat patients with narcolepsy: Harmony III Study.

STUDY OBJECTIVES: To asses the long-term safety and efficacy of pitolisant, an histamine H3-receptor antagonist, on narcolepsy. METHODS: This open-label, single-arm, pragmatic study, recruited adult patients with narcolepsy and Epworth Sleepiness Scale (ESS) score ≥12. After a titration period, patients were treated for up to 1 year with oral pitolisant once-a-day at up to 40 mg. Concomitant stimulants and anti-cataplectic agents were allowed. The primary endpoint was safety; secondary endpoints included ESS, cataplexy, and other diary parameters. RESULTS: Patients (n = 102, 75 with cataplexy) received pitolisant, for the first time in 73 of them. Sixty-eight patients (51 with cataplexy) completed the 12-month treatment. Common treatment-emergent adverse events were headache (11.8% of patients), insomnia (8.8%), weight gain (7.8%), anxiety (6.9%), depressive symptoms (4.9%), and nausea (4.9%). Seven patients had a serious adverse effect, unrelated to pitolisant except for a possibly related miscarriage. One-third of patients stopped pitolisant, mostly (19.6%) for insufficient benefit. ESS score decreased by 4.6 ± 0.6. Two-thirds of patients completing the treatment were responders (ESS ≤ 10 or ESS decrease ≥ 3), and one third had normalized ESS (≤10). Complete and partial cataplexy, hallucinations, sleep paralysis, and sleep attacks were reduced by 76%, 65%, 54%, 63%, and 27%, respectively. Pitolisant as monotherapy (43% of patients) was better tolerated and more efficacious on ESS than on add-on, but efficacy was maintained in this last case. CONCLUSIONS: Long-term safety and efficacy of pitolisant on daytime sleepiness, cataplexy, hallucinations, and sleep paralysis is confirmed.

[Relationship between patent foramen ovale and cryptogenic stroke in a retrospective hospital-based study]. / A foramen ovale apertum és a cryptogen stroke kapcsolata. Retrospektív kórházi vizsgálat.

BACKGROUND AND PURPOSE: After routine workup, 23-25% of ischemic strokes etiology remains unknown, i.e. cryptogenic. However, according to international results pathogenic patent foramen ovale (PFO) reveals in 25% of these cases. Aim of our retrospective study to prove the substantial etiological role of PFO-related stroke (PFO-RS) in cryptogenic strokes (CS), and to identify age related differences in stroke etiology. METHODS: All new ischemic strokes of 2014-2015 were classified by ASCOD (Atherosclerosis, Small-vessel disease, Cardiac pathology, Other, Dissection) phenotyping. CS was defined when the etiology was unknown. With the help of special ultrasound techniques and RoPE (Risk of Paradoxical Embolism) score the portion of PFO-RS were determined in the examined CS population. Moreover, etiological distribution and differences between age groups (<40, 40-60, >60 years) were described. RESULTS: During the examined period, 8.12% of 985 new ischemic strokes were categorized as CS. 41.38% of examined CS were found to be PFO-related. PFO-RS were considerably more frequent in the younger age groups than in the older age groups. The probability of appearance of PFO-RS were significantly higher in younger age than in case of age independency. Our results verify the substantial etiological role of PFO-RS in CS, and confirm the essential role of contrast enhanced functional transcranial Doppler in the routine diagnostic workup. Age related differences in stroke etiology were found to be statistically significant (p=0.000, df=14), in which small-vessel disease, cardiac pathology, dissection, other pathologies, CS and PFO-RS were contributed significantly. CONCLUSION: Based on our results, till in young age rare etiologies are typical, while in older age classical etiologies are mainly characteristic.

Hydrogen bonding effects on the fluorescence properties of 4'-diethylamino-3-hydroxyflavone in water and water-acetone mixtures.

The fluorescence properties of 4'-diethylamino-3-hydroxyflavone (FET), a dye probe sensitive to the polarity as well as the hydrogen bonding ability of its environment, have been studied in acetone-water mixtures by measuring spectra and decay curves over the whole composition range and analyzing the results on the basis of theoretical calculations. In acetone, like in most of organic solvents, the dye showed dual fluorescence, due to an excited state intramolecular proton transfer (ESIPT), in which a quasi-equilibrium between the two excited species, N* and T*, was reached. In acetone-water mixtures with lower molar fractions of water, where the water molecules are largely dispersed, only one type of hydrate could be detected, a complex with 1:1 composition, showing only N* emission, but with a high (0.45) fluorescence quantum yield. At higher water concentrations, the interaction of FET with the hydrogen-bonded water clusters resulted in fluorescence quenching. In neat water the fluorescence quantum yield fell to ~0.001. Theoretical calculations on a FET-acetone complex, a FET-water complex and a FET-water-acetone triple complex (the latter as model for the samples with low water concentrations) concluded that ESIPT was energetically favored in all the models, but the E(N*)-E(T*) energy difference for the water complexes was much lower. The kinetic barrier of ESIPT was found greatly higher in the FET-water complex than in the isolated solute. The intermolecular hydrogen bonds in the water complexes became significantly stronger following the excitation, stabilizing the N* form of the hydrated dye.

Selective counting and sizing of single virus particles using fluorescent aptamer-based nanoparticle tracking analysis.

Detection and counting of single virus particles in liquid samples are largely limited to narrow size distribution of viruses and purified formulations. To address these limitations, here we propose a calibration-free method that enables concurrently the selective recognition, counting and sizing of virus particles as demonstrated through the detection of human respiratory syncytial virus (RSV), an enveloped virus with a broad size distribution, in throat swab samples. RSV viruses were selectively labeled through their attachment glycoproteins (G) with fluorescent aptamers, which further enabled their identification, sizing and counting at the single particle level by fluorescent nanoparticle tracking analysis. The proposed approach seems to be generally applicable to virus detection and quantification. Moreover, it could be successfully applied to detect single RSV particles in swab samples of diagnostic relevance. Since the selective recognition is associated with the sizing of each detected particle, this method enables to discriminate viral elements linked to the virus as well as various virus forms and associations.

Experimental evidence of TICT state in 4-piperidinyl-1,8-naphthalimide - a kinetic and mechanistic study.

The excited state processes in N-propyl-4-piperidinyl-1,8-naphthalimide have been studied by measuring its fluorescence spectra and decay curves in solvents of different polarity and viscosity and also in a frozen solvent glass. The results unanimously proved the formation of a dark twisted intramolecular charge transfer (TICT) state from the emissive charge transfer (CT) species, the direct product of excitation. The rate coefficients of the TICT process and the deactivations of the CT and TICT species were determined, using a reversible two-state kinetic model. The temperature dependence of the kinetic data was consistent with a kinetic barrier consisting of three terms, the inherent barrier of the reaction, and the contributions of the solute-solvent interactions related to the solvent viscosity and polarity. The potential energy surfaces were calculated in the S0 and the S1 states along the coordinate of turning motion which was conclusive concerning the direction of the twisting and indicated a possible conformational change of the piperidinyl unit. The theoretical calculations confirmed that the TICT species is dark and has a stronger charge transfer character compared to the CT state.

Continuous Synthesis and Purification by Coupling a Multistep Flow Reaction with Centrifugal Partition Chromatography.

Continuous-flow multistep synthesis is combined with quasi-continuous final-product purification to produce pure products from crude reaction mixtures. In the nucleophilic aromatic substitution of 2,4-difluoronitrobenzene with morpholine followed by a heterogeneous catalytic hydrogenation, the desired monosubstituted product can be continuously separated from the co- and by-products in a purity of over 99 % by coupling a flow reactor sequence to a multiple dual-mode (MDM) centrifugal partition chromatography (CPC) device. This purification technique has many advantages over HPLC, such as higher resolution and no need for column replacement or silica recycling, and it does not suffer from irreversible adsorption.

Aptamers for respiratory syncytial virus detection.

The identification of the infectious agents is pivotal for appropriate care of patients with viral diseases. Current viral diagnostics rely on selective detection of viral nucleic acid or protein components. In general, detection of proteins rather than nucleic acids is technically more suitable for rapid tests. However, protein-based virus identification methods depend on antibodies limiting the practical applicability of these approaches. Aptamers rival antibodies in target selectivity and binding affinity, and excel in terms of robustness and cost of synthesis. Although aptamers have been generated for virus identification in laboratory settings, their introduction into routine virus diagnostics has not been realized, yet. Here, we demonstrate that the rationally designed SELEX protocol can be applied on whole virus to select aptamers, which can potentially be applied for viral diagnostics. This approach does not require purified virus protein or complicated virus purification. The presented data also illustrate that corroborating the functionality of aptamers with various approaches is essential to pinpoint the most appropriate aptamer amongst the panel of candidates obtained by the selection. Our protocol yielded aptamers capable of detecting respiratory syncytial virus (RSV), an important pathogen causing severe disease especially in young infants, at clinically relevant concentrations in complex matrices.