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

Result code in 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>

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30104 - Pharmacology and pharmacy

Project

<a href="/en/project/EH23_021%2F0008442" target="_blank" >EH23_021/0008442: Pre-application research of drugs for oncological diseases and for the prevention and treatment of serious complications caused by them</a><br>

Continuities

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

Publication year

2025

Confidentiality

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

Name of the periodical

Influenza and Other Respiratory Viruses

ISSN

1750-2640

e-ISSN

1750-2659

Volume of the periodical

19

Issue of the periodical within the volume

10

Country of publishing house

GB - UNITED KINGDOM

Number of pages

15

Pages from-to

e70166

UT code for WoS article

001588522500001

EID of the result in the Scopus database

2-s2.0-105017832667