Compound from Algerian Desert Plant Shows Antifungal Activity and SARS-CoV-2 Binding in Lab Tests

Chemists have isolated a pentacyclic triterpenoid compound from the aerial parts of Launaea arborescens, a shrub widely distributed in southwestern Algeria, and report that it inhibits the growth of several Candida fungal species in laboratory assays while also showing favorable computed binding to the SARS-CoV-2 main protease. The compound, abbreviated HIHPT for heptamethyl–icosahydropicene–triol, was identified as 4,4,6b,8a,11,11,14b-heptamethyl-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-icosahydropicene-3,5,8-triol, a molecule carrying three hydroxyl groups on a five-ring carbon skeleton.

The extraction began with powdered, dehydrated aerial parts of the plant processed through a Soxhlet apparatus using solvents of increasing polarity: diethyl ether, dichloromethane, ethyl acetate, and n-butanol. The dichloromethane extract showed the highest biological activity among the crude fractions and was therefore selected for purification. Silica gel column chromatography with chloroform/petroleum ether and chloroform/methanol gradient elution yielded five fractions, and the bioactive compound was isolated from the fifth fraction as a white powder melting at 62 to 63 degrees Celsius. Spectroscopic characterization by infrared, proton and carbon nuclear magnetic resonance, and mass spectrometry established the molecular formula C29H48O3, with elemental analysis closely matching the calculated carbon, hydrogen, and oxygen percentages.

The antifungal evaluation used five clinical fungal isolates obtained from the Microbiology Laboratory of the University Hospital of Annaba, Algeria: Candida albicans, Candida krusei, Candida kefyr, Candida lusitaniae, and Candida tropicalis. Susceptibility was determined by the agar well diffusion method following Clinical and Laboratory Standards Institute guidelines. A stock solution of 5 milligrams of HIHPT per milliliter of dimethyl sulfoxide was prepared freshly under sterile conditions, and 20 microliters were dispensed into 6-millimeter wells punched into Sabouraud Dextrose Agar plates seeded with fungal suspensions adjusted to 0.5 McFarland turbidity. Amphotericin B served as the positive control, while the solvent and sterile distilled water served as negative controls. Plates were incubated at 37 degrees Celsius for 24 hours, and inhibition zones were measured in millimeters.

The results showed activity against four of the five tested species. The strongest effect appeared against Candida krusei, with a 35-millimeter inhibition zone compared with 20 millimeters for amphotericin B, a notable result because C. krusei is recognized for its intrinsic resistance to several conventional antifungal agents. Against Candida albicans, HIHPT produced a 28-millimeter zone while amphotericin B was recorded as resistant, meaning no measurable inhibition under the assay conditions. Candida lusitaniae showed a 22-millimeter zone with HIHPT, again with the reference drug recorded as resistant, and Candida tropicalis displayed a 16-millimeter zone for HIHPT versus 8 millimeters for amphotericin B. No activity was observed against Candida kefyr, and the DMSO negative control produced no inhibition for any strain, indicating the observed effects were attributable to the compound itself.

Beyond planktonic growth, the team assessed biofilm formation using a crystal violet staining assay in 96-well polystyrene plates, measuring optical density at 620 nanometers after 24 hours of incubation. HIHPT inhibited biofilm formation across all five Candida isolates, with the highest inhibition against Candida albicans at 46.54 percent, followed by Candida kefyr at 36.46 percent, Candida lusitaniae at 33.87 percent, Candida krusei at 30.90 percent, and Candida tropicalis at 22.77 percent. Amphotericin B, by contrast, showed only weak biofilm inhibition against C. krusei and C. tropicalis and little or no inhibition against the remaining species under the same conditions. Because biofilm formation is a major virulence factor contributing to antifungal resistance and recurrent candidiasis, compounds that suppress it are considered promising leads, although the authors note that minimum inhibitory concentration, minimum fungicidal concentration, and mechanistic studies are still needed to validate the antifungal potential.

On the computational side, the researchers docked HIHPT into the SARS-CoV-2 main protease, Mpro, using the Glide Standard Precision protocol in the Schrödinger Suite after validating the protocol by re-docking the co-crystallized ligand, methyl 4-sulfamoylbenzoate, with a root-mean-square deviation below 1.0 angstrom. HIHPT achieved a docking score of −5.913 kcal/mol and a binding energy of −45.525 kcal/mol, comparable to the reference ligand’s −6.518 kcal/mol and −47.112 kcal/mol. The docked pose formed two hydrogen bonds with Glu166 and Pro168, residues involved in substrate recognition and inhibitor stabilization, plus hydrophobic alkyl and pi-alkyl contacts with Met49 and Met165 in the S2 subsite. These docking results indicate a stable predicted binding conformation but do not by themselves demonstrate antiviral efficacy.

Molecular dynamics simulations extended the docking analysis over 100 nanoseconds for two systems: the protease bound to the positive control compound Z18197050 and the protease bound to HIHPT. The root-mean-square deviation of C-alpha atoms settled near 2.4 angstroms for the control system and about 2.0 angstroms for the HIHPT complex, suggesting both systems equilibrated without major conformational change in the protease. Residues in contact with either ligand fluctuated by less than 6.0 angstroms. Because the simulation was implicit-solvent, water-mediated hydrogen-bonded interactions appeared with Glu166, Val186, Arg188, Gln189, Thr190, and Gln192 for the control, and with His41, Ser46, Asn142, Glu146, Gln189, and Thr190 for HIHPT, with Gln189 and Thr190 common to both complexes. Hydrophobic contacts involved Met49 and Met165 for the control and Met65 and Pro168 for the extracted compound.

MM-GBSA binding free energy calculations on twenty snapshots taken at 5-nanosecond intervals showed consistently negative energies for both complexes. The control ranged from approximately −16.93 to −42.96 kcal/mol, with strain-corrected values from −17.37 to −44.01 kcal/mol, while HIHPT ranged from about −22.73 to −38.27 kcal/mol, or −23.73 to −39.01 kcal/mol with strain correction. The control generally bound more favorably, particularly near the end of the trajectory, but HIHPT maintained stable interaction energies throughout without significant fluctuations, and the small 1 to 3 kcal/mol differences between corrected and uncorrected values indicated minimal ligand conformational strain. The authors interpret this as thermodynamically favorable binding that warrants further biological validation rather than as evidence of inhibition.

Additional quantum chemical and property calculations rounded out the profile. Density functional theory at the B3LYP/6-31G(d,p) level yielded a HOMO-LUMO gap of 6.632 electron volts for HIHPT, close to the two reference ligands, with frontier orbitals localized on the cyclic portion of the molecule. Natural bond orbital charges identified the hydroxyl oxygen atoms as the most negative sites and hydroxyl hydrogens as the most positive, consistent with the molecular electrostatic potential map. Online property predictors estimated a cLogP near 5.3, no predicted mutagenicity, tumorigenicity, irritation, or reproductive toxicity risks, a drug-likeness score of −2.42, and a drug score of 0.21. A calculated intrinsic log P of 4.56 and intrinsic solubility of −4.85 log mol/L indicated a strongly lipophilic, poorly water-soluble neutral molecule that remains largely non-ionized between pH 1 and 12, which the authors note may limit aqueous dissolution and oral bioavailability absent formulation strategies.

Taken together, the study positions HIHPT as a natural lead compound whose measured antifungal activity against clinical Candida isolates and predicted binding to SARS-CoV-2 Mpro justify further investigation. The authors themselves frame the conclusion cautiously: in vitro assays, docking, dynamics simulations, and property analyses revealed favorable biological activity, stable target interactions, and acceptable drug-like characteristics, but in vivo studies and clinical investigations are required to validate therapeutic efficacy and safety. For now, the findings add to the documented chemical diversity of Saharan medicinal flora and illustrate how traditional-use plants can yield structurally interesting triterpenoids for modern screening pipelines, while the gap between a laboratory inhibition zone and a clinically useful medicine remains substantial.

Subject of Research: Isolation of the triterpenoid HIHPT from Launaea arborescens and its in vitro antifungal activity and computational assessment against SARS-CoV-2 targets

Article Title: Integrative experimental and computational assessment of HIHPT from Algerian medicinal plants against SARS-CoV-2 and pathogenic microbes

Article References: Bouasla, R., Berredjem, M., Acidi, A., Rachedi, K. O., Benzaid, C., Dekir, A., Ferkous, H., Cheriti, A., Djouad, S.-E., Ahmed, S., Hajam, Y. A., Bhat, A. R., & Agisho, H. A. (2026). Integrative experimental and computational assessment of HIHPT from Algerian medicinal plants against SARS-CoV-2 and pathogenic microbes. Results in Chemistry, 32, Article 103999. https://doi.org/10.1016/j.rechem.2026.103999

Image Credits: AI Generated

DOI: 10.1016/j.rechem.2026.103999

Keywords: Launaea arborescens, HIHPT, triterpenoid, antifungal, Candida, biofilm inhibition, SARS-CoV-2, main protease, molecular docking, molecular dynamics, MM-GBSA, Algerian medicinal plants