Anticoronavirus Isoquinoline Alkaloids: Unraveling the Secrets of Their Structure-Activity Relationship

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F25%3A10505614" target="_blank" >RIV/00216208:11160/25:10505614 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=.0U_t_-DvB" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=.0U_t_-DvB</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/irv.70166" target="_blank" >10.1111/irv.70166</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Anticoronavirus Isoquinoline Alkaloids: Unraveling the Secrets of Their Structure-Activity Relationship

Popis výsledku v původním jazyce

Background: Natural alkaloids are a structurally diverse class of bioactive compounds with significant therapeutic potential. This study aimed to evaluate the in vitro antiviral activity of various natural alkaloids against coronaviruses, clarify molecular effects via bioassays and docking, and explore structure-activity relationships. Tested compounds included a wide variety of isoquinoline and Amaryllidaceae-type alkaloids. Methodology: Antiviral activity was assessed using HCoV-229E and pseudotyped lentivirus assays for different strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cytotoxicity was evaluated with the WST-1 assay. AutoDock was used for molecular docking, online tools assessed drug-likeness, and ChemGPS-NP analyzed physicochemical properties correlated to antiviral clinical drugs. Results: Several bis-benzylisoquinoline alkaloids, especially from Berberis vulgaris L., and specific Amaryllidaceae alkaloids showed protective activity against HCoV-229E (EC50 = 4.1-8.1 mu M). Active compounds were further tested against SARS-CoV-2 variants. Aromoline (Compound 16) exhibited strong antiviral activity, inhibiting D614G, Delta, and Omicron variants in pseudovirus assays with IC50 values of 0.47-0.66 mu M. Other bis-benzylisoquinoline analogues showed moderate activity (IC50 = 1.24-2.86 mu M). Docking studies revealed aromoline&apos;s favorable interaction at the SARS-CoV-2 spike/ACE2 interface, forming hydrogen bonds with Gln493 and Ser494 (binding energy -5.34 kcal/mol). ChemGPS-NP analysis highlighted a distinct cluster of active bis-benzylisoquinolines (Compounds 16-19) in chemical space. Conclusion: This study highlights the antiviral potential of bis-benzylisoquinoline and Amaryllidaceae alkaloids, particularly aromoline. The findings support their relevance as scaffolds for developing novel anticoronavirus agents and advance the understanding of their structure-activity relationships.

Název v anglickém jazyce

Anticoronavirus Isoquinoline Alkaloids: Unraveling the Secrets of Their Structure-Activity Relationship

Popis výsledku anglicky

Background: Natural alkaloids are a structurally diverse class of bioactive compounds with significant therapeutic potential. This study aimed to evaluate the in vitro antiviral activity of various natural alkaloids against coronaviruses, clarify molecular effects via bioassays and docking, and explore structure-activity relationships. Tested compounds included a wide variety of isoquinoline and Amaryllidaceae-type alkaloids. Methodology: Antiviral activity was assessed using HCoV-229E and pseudotyped lentivirus assays for different strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cytotoxicity was evaluated with the WST-1 assay. AutoDock was used for molecular docking, online tools assessed drug-likeness, and ChemGPS-NP analyzed physicochemical properties correlated to antiviral clinical drugs. Results: Several bis-benzylisoquinoline alkaloids, especially from Berberis vulgaris L., and specific Amaryllidaceae alkaloids showed protective activity against HCoV-229E (EC50 = 4.1-8.1 mu M). Active compounds were further tested against SARS-CoV-2 variants. Aromoline (Compound 16) exhibited strong antiviral activity, inhibiting D614G, Delta, and Omicron variants in pseudovirus assays with IC50 values of 0.47-0.66 mu M. Other bis-benzylisoquinoline analogues showed moderate activity (IC50 = 1.24-2.86 mu M). Docking studies revealed aromoline&apos;s favorable interaction at the SARS-CoV-2 spike/ACE2 interface, forming hydrogen bonds with Gln493 and Ser494 (binding energy -5.34 kcal/mol). ChemGPS-NP analysis highlighted a distinct cluster of active bis-benzylisoquinolines (Compounds 16-19) in chemical space. Conclusion: This study highlights the antiviral potential of bis-benzylisoquinoline and Amaryllidaceae alkaloids, particularly aromoline. The findings support their relevance as scaffolds for developing novel anticoronavirus agents and advance the understanding of their structure-activity relationships.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

<a href="/cs/project/EH23_021%2F0008442" target="_blank" >EH23_021/0008442: Předaplikační výzkum léčiv pro onkologická onemocnění a pro prevenci a léčbu jimi navozených závažných komplikací (OncoPharm)</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Influenza and Other Respiratory Viruses

ISSN

1750-2640

e-ISSN

1750-2659

Svazek periodika

19

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

15

Strana od-do

e70166

Kód UT WoS článku

001588522500001

EID výsledku v databázi Scopus

2-s2.0-105017832667