bims-antpol 2025-01-12 papers

Issue of 2025–01–12
six papers selected by
Rick Sheridan, EMSKE Phytochem

Chem Biodivers. 2025 Jan 10. e202402661

Uncovering Antiviral Potential of Cistus ladanifer Extracts Against HSV-1 and SARS-CoV-2 by In Vitro and In Silico Analysis.

Kaoutar Bouothmany, Mohammed Bourhia, Mohammed Chebaibi, Zineb Rhazzar, Boutaina Addoum, Farid Khallouki, Mohamed El Mzibri, Mosatafa Elouennass, Khalid Ennibi, Khalid S Almaary, Muhammad Usman Qamar, Nadia Touil, Laila Benbacer.

Infectious diseases remain a major global health concern. Cistus ladanifer, a plant commonly employed in Moroccan traditional medicine, has been identified as a potential antiviral candidate. This study aimed to evaluate the antiviral activity of C. ladanifer extracts in vitro and in silico against two respiratory viruses: Herpes simplex virus and the severe acute respiratory syndrome coronavirus 2 variants of concern Delta and Omicron. Toxic prediction of the main compounds identified by Gas Chromatography-Mass Spectrometry from Cistus ladanifer was performed in silico via ProTox-II software. Molecular docking was subsequently performed via Maestro version 11.5 software from Schrödinger to gain a comprehensive understanding of their biological activity. The extracts were subjected to in vitro antiviral screening against the selected strains via real-time RT‒qPCR. Our docking estimation supported the in vitro results, and a diverse array of compounds extracted from Cistus ladanifer demonstrated significant antiviral activity with a low toxicity profile. Accordingly, in vitro data revealed a dose-dependent effect of the studied extracts, with particular efficacy against the Omicron variant. With the antiviral evaluation and docking outcomes in hand, we suggest a plausible mechanism of action for these compounds through further investigation into the effectiveness of Cistus ladanifer against other respiratory viruses.

Keywords: Antiviral; C.ladanifer; Infectious; Medicinal plants; in vitro

DOI: https://doi.org/10.1002/cbdv.202402661

Drug Dev Ind Pharm. 2025 Jan 04. 1-14

Potent antiviral action detected in Tontelea micrantha extracts against Alphavirus chikungunya.

Ranieli Paiva Lopes, Millena Alves Máximo Vaz, Fernanda Lopes Ferreira, Grasiely Faria de Sousa, Cintia Lopes de Brito Magalhães, Sidney Augusto Vieira-Filho, Jaqueline Maria Siqueira Ferreira, Antônio Helvécio Tótola, Lucienir Pains Duarte, José Carlos de Magalhães.

BACKGROUND: Tontelea micrantha, a notable plant species, has garnered interest for its medicinal properties, including anti-inflammatory, antibacterial and antiviral effects. A vaccine for Chikungunia virus is still under evaluation and no specific antiviral drug has been licensed to date.
OBJECTIVE: The work investigated antiviral activity of ethyl acetate (EAEF) and methanolic (EMF) extracts from T. micrantha leaves in mammalian cells exposed to Alphavirus chikungunya (CHIKV). This plant species showed remarkable medicinal properties including anti-inflammatory, antiviral and antibacterial effects.
METHODS: The cytotoxicity, antiviral activity, selectivity index, effect on viral gene expression, virus production, and mechanisms of action were evaluated.
RESULTS: EAEF and EMF extracts showed anti-CHIKV effects at non-cytotoxic concentrations, with CC50 above 300μg/mL, EC50 of 18 and 43 μg/mL respectively, and selectivity Index above 4. These concentrations drastically reduce viral yields and CHIKV gene expression and have shown activity both directly on viral particles and at different stages of the viral cycle.
CONCLUSION: EAEF and EMF showed robust antiviral activity against CHIKV, making them promising candidates for the development of anti-CHIKV drugs.

Keywords: Alphavirus chikungunya; Antiviral mechanisms; Selectivity index; Tontelea micrantha extracts; Virucidal activity; anti-CHIKV effect

DOI: https://doi.org/10.1080/03639045.2024.2449130

Saudi Med J. 2025 Jan;46(1): 26-35

Ajwa date extract (Phoenix dactylifera L.): Phytochemical analysis, antiviral activity against herpes simplex virus-I and coxsackie B4 virus, and in silico study.

Ahmad K Aljohani, Nader A Maghrabi, Osama M Alrehili, Abdulaziz S Alharbi, Rawad S Alsihli, Abdulrahman M Alharthe, Rayan S Albladi, Khalid A Alosaimi, Bader M Albadrani, Samar F Miski, Hossein M Elbadawy, Bandar D Alrehaili, Fahd A Abdelkarem, Modather F Hussein.

OBJECTIVES: To investigate the phytochemical composition of Ajwa date extract and evaluate its antiviral activity and mechanism of action.
METHODS: High perfomance liquid chromatography, gas chromatography-mass spectrometry, and liquid chromatography-mass spectrometry were used to analyze the phytochemical profile of Ajwa date extract. The antiviral activity was assessed using the MTT colorimetric assay against herpes simplex virus type I (HSV-I) and coxsackievirus B4 (CVB-4). Assessment of the mechanism of action against HSV-I was carried out using 3 protocols. Molecular docking and quantum chemical calculations were carried out to predict the binding affinities of the identified compounds to viral glycoprotein D.
RESULTS: A total of 17 metabolites belonging to different classes of metabolites, mainly flavonoids, phenolic acid derivatives, fatty acids, and sugar derivatives. Ajwa extract exhibited antiviral activity against HSV-I with an IC: 50 of 113.99±4.67 μg/mL, whereas it showed limited activity against CVB-4. The antiviral activity of Ajwa extract was mainly attributed to its cell protectant activity by preventing adherence of viral to host cell with an IC: 50 equal to 57.82±1.37μg/mL. Molecular docking studies indicated that chlorogenic acid had the strongest binding affinity to viral glycoprotein D, which suggests its potential role in inhibiting viral entry into host cells.
CONCLUSION: The Ajwa date extract demonstrated promising antiviral activity, especially against HSV-I. Integrating in vitro and in silico analyses provided valuable insights into the mechanisms of action.

Keywords: Ajwa dates; antiviral activity; gas chromatography-mass spectrometry; high-performance liquid chromatography; molecular docking

DOI: https://doi.org/10.15537/smj.2025.46.1.20240780

Phytomedicine. 2024 Dec 29. pii: S0944-7113(24)01014-6. [Epub ahead of print]136 156359

Recent advances in phytocompounds as potential Chikungunya virus non-structural protein 2 protease antagonists: A systematic review.

Jarmani Dansana, Priyanka Purohit, Madhusmita Panda, Biswa Ranjan Meher.

BACKGROUND: The mosquito-borne pathogenic alphavirus known as Chikungunya virus (CHIKV) is becoming a greater hazard to public health, which causes thousands of cases annually in both rural and urban areas of many different nations throughout the world. Finding and creating new leads for the CHIKV virus is crucial because there are currently no effective medications or vaccinations against it. The non-structural protein 2 (nsP2) protease has emerged as a promising target for therapeutic intervention due to its crucial role in viral replication.
PURPOSE: This systematic review aims to evaluate recent advances in natural products as inhibitors of the CHIKV nsP2 protease, summarizing current research, identifying promising compounds, and highlighting gaps in the existing knowledge.
STUDY DESIGN: A comprehensive literature search was conducted between January 2006, and June 2024 using databases including PubMed, Scopus, Science Direct, and Google Scholar. Search terms included CHIKV, nsP2 protease, antivirals, natural products, phytochemicals, and inhibitors. Studies were selected based on predefined inclusion and exclusion criteria, focusing on original research articles examining natural products as inhibitors of CHIKV nsP2 protease.
METHODS: Relevant studies were screened, and data were extracted regarding the source of natural compounds, methods of extraction, chemical structures, mechanisms of action, potency, and efficacy in inhibiting nsP2 protease or CHIKV replication.
RESULTS: The review included 40 studies, revealing a variety of natural products and their derivatives with inhibitory effects on CHIKV nsP2 protease. Several compounds demonstrated promising inhibitory activity with EC50 values in the micromolar range. Mechanistic studies revealed diverse modes of action, including inhibition of protease activity or interference with viral replication processes.
CONCLUSION: Natural products have gained attention for their diverse chemical structures and bioactivities, offering a rich source of compounds with antiviral potential. We summarize the current knowledge on natural products derived from various sources including flavonoids, alkaloids, terpenoids, polyphenols, and some derivative compounds that have demonstrated inhibitory effects against CHIKV through different mechanisms of action. Overall, this systematic review underscores the importance of exploring natural products as promising candidates for the development of effective therapeutics against Chikungunya fever, particularly through targeting the nsP2 protease.

Keywords: CHIKV; antiviral drug development; inhibitors; natural products; nsP2 protease; phytochemicals

DOI: https://doi.org/10.1016/j.phymed.2024.156359

Foods. 2024 Dec 11. pii: 4008. [Epub ahead of print]13(24):

Antiviral Potential of Spiraea Extracts (Prepared by Repercolation) Against Influenza A (H1N1) Virus.

Vera A Kostikova, Yana L Esaulkova, Polina A Ilyina, Vladimir V Zarubaev, Vladimir V Sheikin, Anastasia A Petruk, Ekaterina D Rubtsova, Tatiana N Veklich.

An antiviral effect of extracts prepared from aerial parts of nine species and from leaves of two species of the genus Spiraea L. was investigated for potential antiviral activity toward influenza A (H1N1) virus. The toxicity of dry extracts was analyzed, and the most selective extract was identified in vitro. The study's material was collected in the Asian part of Russia. The plant extracts were prepared via three-stage countercurrent repercolation involving a complete cycle. All 40%-ethanolic extracts from Spiraea manifested antiviral activity against influenza A (H1N1) virus, with a selectivity index (SI) ranging from 1 to 10. IC50 values indicated that the S. salicifolia L. S15 leaf extract (5.9 µg/mL) has the most pronounced antiviral effect and the lowest toxicity (CC50 = 57.6 µg/mL) among the studied samples. The SI of this extract was 10, which exceeded that of the antiviral agent rimantadine (SI = 6). Biologically active compounds in the extract with the highest antiviral activity were identified using UV spectrometry and high-performance liquid chromatography. The S. salicifolia leaf extract was found to contain phenolic acids (chlorogenic, gentisic, caffeic, ferulic, and cinnamic acids), flavonols (quercetin, quercetin-3-glucuronoside, hyperoside, isoquercitrin, rutin, spiraeoside, avicularin, quercitrin, kaempferol, nicotiflorin, astragalin, and isorhamnetin-3-rutinoside), flavones (orientin, luteolin-7-glucoside, and vitexin), and coumarin. Predominant biologically active compounds in the S. salicifolia S15 leaf extract were such flavonols as rutin (19.3 mg/g), isoquercitrin (16.6 mg/g), isorhamnetin-3-rutinoside (10.6 mg/g), and astragalin (9.5 mg/g). Extraction of S. salicifolia leaves by repercolation is a more suitable method for extracting active ingredients with an antiviral effect.

Keywords: Spiraea; antiviral activity; biologically active compound; repercolation

DOI: https://doi.org/10.3390/foods13244008

Viruses. 2024 Dec 17. pii: 1929. [Epub ahead of print]16(12):

In Vitro Evaluation of the Anti-Chikungunya Virus Activity of an Active Fraction Obtained from Euphorbia grandicornis Latex.

José Angel Santiago-Cruz, Araceli Posadas-Mondragón, Angélica Pérez-Juárez, Norma Estela Herrera-González, José Miguel Chin-Chan, Joab Eli Aguilar-González, José Leopoldo Aguilar-Faisal.

Chikungunya virus (CHIKV) is classified as a pathogen with the potential to cause a pandemic. This situation becomes more alarming since no approved drug exists to combat the virus. The present research aims to demonstrate the anti-CHIKV activity of molecules present in the latex of Euphorbia grandicornis. Therefore, a biodirected assay was carried out to find the molecules with anti-CHIKV activity. Extractions with hexane, dichloromethane, and methanol and subsequent purification by column chromatography were carried out to later evaluate cytotoxic activity by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and antiviral activity by plaque assay. Our findings show that unlike the others, methanolic extract has a low cytotoxic effect and a good anti-CHIKV effect (EC50 = 26.41 µg/mL), which increases when obtaining the purified active fraction (pAFeg1) (EC50 = 0.4835 µg/mL). Time-of-addition suggests that the possible mechanism of action of pAFeg1 could be inhibiting any of the non-structural proteins of CHIKV. In addition, both the cytotoxic and anti-CHIKV activity of pAFeg1 demonstrate selectivity since it killed cancer cells and could not inhibit DENV2.

Keywords: Euphorbia grandicornis; antiviral; cancer cells; chikungunya virus; cytotoxic; latex; oleanolic acid; roburic acid; selectivity

DOI: https://doi.org/10.3390/v16121929