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RNA viruses pose a persistent global threat due to their high mutation rates, zoonotic potential, and rapid adaptability. Emergence events have risen steadily, as demonstrated by major outbreaks caused by Influenza A, Ebola, Zika, and Chikungunya viruses, followed by the coronavirus epidemics of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-1) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and culminating in the COVID-19 pandemic. These characteristics frequently compromise the durability of existing vaccines and antiviral therapies, highlighting the urgent need for new antiviral agents. Alkaloids, a structurally diverse class of nitrogen-containing natural compounds, have gained attention for their ability to interfere with multiple stages of the viral life cycle, including entry, replication, protein synthesis, and host immune modulation. To our knowledge, this review compiles all currently reported alkaloids with antiviral activity against RNA viruses and summarizes their proposed mechanisms of action, distinguishing evidence from in vitro, in vivo, and in silico studies. Quaternary alkaloids are discussed separately because their permanent ionic charge enables distinctive interactions with membranes and host pathways. Although many findings are promising, clinical translation remains limited by incomplete mechanistic validation, scarce in vivo data, suboptimal bioavailability, narrow therapeutic windows, and inconsistent experimental methodologies. To advance the field, future research should prioritize RT-qPCR–based antiviral evaluation to accurately quantify viral replication, incorporate mechanistic assays to clarify modes of action, apply structure–activity relationship (SAR) approaches for rational optimization, and expand in vivo pharmacokinetic and efficacy studies to assess therapeutic feasibility. Overall, alkaloids represent a promising yet underdeveloped reservoir for next-generation antiviral discovery against rapidly evolving RNA viruses.

A new dimeric aporphine alkaloid, biscocsarmine, 2, together with lirioferine, 1, and cocsarmine, 3, were isolated from the ethanol extract of the stems of Triclisia dictyophylla Diels (Menispermaceae) using a preparative pH-zone refining CCC in a single step. The first solvent system family tested for this fractionation was hexane–ethyl acetate–methanol–water (HEMWat) at a series of solvent ratios, and hydrochloric acid and triethylamine at 5 mM as eluter/retainer. None of these HEMWat ratios, however, gave suitable K for the target alkaloids. Ethyl acetate–n-butanol–water (EBuWat) was tested instead and the selected solvent system was composed of ethyl acetate–n-butanol–water 5:5:10 (v/v), where triethylamine (60 mM) was added to the upper organic stationary phase as a retainer and hydrochloric acid (5 mM) to the aqueous mobile phase as an eluter. The chemical structures of the isolated compounds were elucidated based on comprehensive spectroscopic and spectrometric techniques. This is the first report of aporphine alkaloids in this plant species.

Quaternary alkaloids are the major alkaloids isolated from Tinospora species. A previous study pointed to the necessary presence of quaternary nitrogens for strong acetylcholinesterase (AChE) inhibitory activity in such alkaloids. Repeated column chromatography of the vine of Tinospora crispa extract led to the isolation of one new protoberberine alkaloid, 4,13-dihydroxy-2,8,9-trimethoxydibenzo[a,g]quinolizinium (1), along with six known alkaloids—dihydrodiscretamine (2), columbamine (3), magnoflorine (4), N-formylannonaine (5), N-formylnornuciferine (6), and N-trans-feruloyltyramine (7). The seven compounds were isolated and structurally elucidated by spectroscopic analysis. Two known alkaloids, namely, dihydrodiscretamine and columbamine are reported for the first time for this plant. The compounds were tested for AChE inhibitory activity using Ellman’s method. In the AChE inhibition assay, only columbamine (3) showed strong activity with IC50 48.1 µM. The structure–activity relationships derived from these results suggest that the quaternary nitrogen in the skeleton has some effect, but that a high degree of methoxylation is more important for acetylcholinesterase inhibition.

Main-chain chiral quaternary ammonium polymers were successfully synthesized by the quaternization polymerization of cinchonidine dimer with dihalides. The polymerization occurred smoothly under optimized conditions to give novel type of main-chain chiral quaternary ammonium polymers. The catalytic activity of the polymeric chiral organocatalysts was investigated on the asymmetric benzylation of N-(diphenylmethylidene)glycine tert-butyl ester.

A novel π-conjugated polymer-modified magnetic dendritic fibrous mesoporous silica adsorbent (MB@KCC-1@π-CP) is reported for the accurate determination of quaternary ammonium alkaloids (QAAs) in complex body fluid matrices. It is demonstrated that the magnetic dendritic fibrous mesoporous silica (MB@KCC-1) is an excellent carrier combining magnetism, high specific surface area, unique hierarchical pore structure, and fast mass transfer rate. The π-conjugated polymer (π-CP) can efficiently retain QAAs (berberine, coptisine, palmatine, jatrorrhizine) by multiple interactions. In addition, the adsorption kinetics and adsorption mechanism were also studied and discussed. Under optimized extraction conditions, MB@KCC-1@π-CP-based magnetic solid-phase extraction (MSPE) and high-performance liquid chromatography (HPLC) method affords a wide linear range (0.5-20000 ng mL −1 ), low limits of detection (0.2-2 ng mL −1 ), and satisfactory relative standard deviations (RSD) of inter-day (< 2.4%) and intra-day (< 3.1%) for QAAs. Trace QAAs in complex human blood plasma samples were successfully detected by the established method. Graphical abstract

Summary Achyranthes aspera L. var aspera is much valued in the ayurvedic system of medicine. It is also used as a medicinal plant in other countries. Literature review and chemical investigations in our laboratory showed the presence of alkaloids and triterpenoid saponins. Two alcohol extracts of the plant were analyzed to determine amounts of the alkaloid betaine. Compounds were separated on silica gel 60 F 254 plates with methanol-water 9:1 ( v/v ) as mobile phase. Detection by measurement of absorbance at 550 nm after derivatization with modified Dragendorff’s reagent. The R F value was 0.4. The betaine content of the extracts was calculated statistically. Comparison was made with betaine standard. The method was accurate, precise, repeatable, and reproducible. The linear range of the method was 4–30 µg per band. The robustness and ruggedness of the method was also evaluated. The technique may be used for routine standardization of the betaine content of alcohol extracts of A. aspera .

In order to understand the antifungal activity of some derivatives of sanguinarine (S) and chelerythrine (C) and their structure-activity relationships, sixteen derivatives of S and C were prepared and evaluated for in vitro antifungal activity against seven phytopathogenic fungi by the mycelial growth rate method. The results showed that S, C and their 6-alkoxy dihydro derivatives S1–S4, C1–C4 and 6-cyanodihydro derivatives S5, C5 showed significant antifungal activity at 100 µg/mL against all the tested fungi. For most tested fungi, the median effective concentrations of S, S1, C and C1 were in a range of 14–50 µg/mL. The structure-activity relationship showed that the C=N+ moiety was the determinant for the antifungal activity of S and C. S1–S5 and C1–C5 could be considered as the precursors of S and C, respectively. Thus, the present results strongly suggested that S and C or their derivatives S1–S5 and C1–C5 should be considered as good lead compounds or model molecules to develop new anti-phytopathogenic fungal agents.

An LC–DAD method has been developed in order to evaluate qualitatively and quantitatively quaternary aporphine alkaloids, flavonoid glycosides and styrylpyrones, which are the main secondary metabolites of leaves from C. mandioccana. The chromatographic method was validated considering both internal and external standard quantification methods and showed good performances in terms of selectivity, linearity, precision (repeatability and intermediate precision), limit of detection, limit of quantification, accuracy and stability.

Ribosomally synthesized and post-translationally modified peptide natural products have provided many highly unusual scaffolds. This includes the intriguing alkaloids crocagins, which possess a tetracyclic core structure and whose biosynthesis has remained enigmatic. Here we use in vitro experiments to demonstrate that three proteins, CgnB, CgnC and CgnE, are sufficient for the production of the hallmark tetracyclic crocagin core from the precursor peptide CgnA. The crystal structures of the homologues CgnB and CgnE reveal them to be the founding members of a peptide-binding protein family and allow us to rationalize their distinct functions. We further show that the hydrolase CgnD liberates the crocagin core scaffold, which is subsequently N-methylated by CgnL. These insights allow us to propose a biosynthetic scheme for crocagins. Bioinformatic analyses based on these data led to the discovery of related biosynthetic pathways that may provide access to a structurally diverse family of peptide-derived pyrroloindoline alkaloids.The alkaloids crocagins are derived from a ribosomal peptide through a series of enzymatic post-translational modifications. A combination of biochemistry and structural biology techniques has now been used to elucidate this biosynthetic pathway, propose a mechanism for the formation of the tetracyclic core structure and enable genome mining for related natural products.

Control of molecular chirality is a fundamental challenge in organic synthesis. Whereas methods to construct carbon stereocentres enantioselectively are well established, routes to synthesize enriched heteroatomic stereocentres have garnered less attention 1 – 5 . Of those atoms commonly present in organic molecules, nitrogen is the most difficult to control stereochemically. Although a limited number of resolution processes have been demonstrated 6 – 8 , no general methodology exists to enantioselectively prepare a nitrogen stereocentre. Here we show that control of the chirality of ammonium cations is easily achieved through a supramolecular recognition process. By combining enantioselective ammonium recognition mediated by 1,1′-bi-2-naphthol scaffolds with conditions that allow the nitrogen stereocentre to racemize, chiral ammonium cations can be produced in excellent yields and selectivities. Mechanistic investigations demonstrate that, through a combination of solution and solid-phase recognition, a thermodynamically driven adductive crystallization process is responsible for the observed selectivity. Distinct from processes based on dynamic and kinetic resolution, which are under kinetic control, this allows for increased selectivity over time by a self-corrective process. The importance of nitrogen stereocentres can be revealed through a stereoselective supramolecular recognition, which is not possible with naturally occurring pseudoenantiomeric Cinchona alkaloids. With practical access to the enantiomeric forms of ammonium cations, this previously ignored stereocentre is now available to be explored. Enantioselective supramolecular recognition allows for the asymmetric synthesis of nitrogen stereocentres, providing chiral ammonium cations in a dynamic crystallization process.