دورية أكاديمية

Honokiol Inhibits SARS-CoV-2 Replication in Cell Culture at a Post-Entry Step.

التفاصيل البيبلوغرافية
العنوان: Honokiol Inhibits SARS-CoV-2 Replication in Cell Culture at a Post-Entry Step.
المؤلفون: Salgado-Benvindo C; Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands., Leijs AA; Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands., Thaler M; Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands., Tas A; Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands., Arbiser JL; Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia, USA.; Division of Dermatology, Veterans Affairs Medical Center, Decatur, Georgia, USA., Snijder EJ; Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands., van Hemert MJ; Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
المصدر: Microbiology spectrum [Microbiol Spectr] 2023 Jun 15; Vol. 11 (3), pp. e0327322. Date of Electronic Publication: 2023 May 04.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: ASM Press Country of Publication: United States NLM ID: 101634614 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2165-0497 (Electronic) Linking ISSN: 21650497 NLM ISO Abbreviation: Microbiol Spectr Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : ASM Press, 2013-
مواضيع طبية MeSH: SARS-CoV-2* , COVID-19*, Animals ; Humans ; Antiviral Agents/pharmacology ; Cell Culture Techniques
مستخلص: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019, and the resulting pandemic has already caused the death of over 6 million people. There are currently few antivirals approved for treatment of the 2019 coronavirus disease (COVID-19), and more options would be beneficial, not only now but also to increase our preparedness for future coronavirus outbreaks. Honokiol is a small molecule from magnolia trees for which several biological effects have been reported, including anticancer and anti-inflammatory activities. Honokiol has also been shown to inhibit several viruses in cell culture. In this study, we determined that honokiol protected Vero E6 cells from SARS-CoV-2-mediated cytopathic effect, with a 50% effective concentration of 7.8 μM. In viral load reduction assays, honokiol decreased viral RNA copies as well as viral infectious progeny titers. The compound also inhibited SARS-CoV-2 replication in the more relevant human A549 cells expressing angiotensin converting enzyme 2 and transmembrane protease serine 2. Time-of-addition and other assays showed that honokiol inhibited virus replication at a post-entry step of the replication cycle. Honokiol was also effective against more recent variants of SARS-CoV-2, including Omicron, and it inhibited other human coronaviruses as well. Our study suggests that honokiol is an interesting molecule to be evaluated further in animal studies and, when successful, maybe even in clinical trials to investigate its effect on virus replication and pathogenic (inflammatory) host responses. IMPORTANCE Honokiol is a compound that shows both anti-inflammatory and antiviral effects, and therefore its effect on SARS-CoV-2 infection was assessed. This small molecule inhibited SARS-CoV-2 replication in various cell-based infection systems, with up to an ~1,000-fold reduction in virus titer. In contrast to earlier reports, our study clearly showed that honokiol acts on a postentry step of the replication cycle. Honokiol also inhibited different recent SARS-CoV-2 variants and other human coronaviruses (Middle East respiratory syndrome CoV and SARS-CoV), demonstrating its broad spectrum of antiviral activity. The anticoronavirus effect, combined with its anti-inflammatory properties, make honokiol an interesting compound to be further explored in animal coronavirus infection models.
Competing Interests: The authors declare no conflict of interest.
References: Molecules. 2022 Oct 29;27(21):. (PMID: 36364188)
J Gen Virol. 2013 Aug;94(Pt 8):1749-1760. (PMID: 23620378)
Nucleic Acids Res. 1991 Jun 11;19(11):2993-3000. (PMID: 2057357)
Cancer Lett. 2016 Jan 1;370(1):66-77. (PMID: 26454217)
Nature. 1992 Jun 4;357(6377):420-2. (PMID: 1350662)
Front Oncol. 2021 Oct 04;11:728583. (PMID: 34671554)
J Cell Physiol. 2012 May;227(5):2184-95. (PMID: 21792937)
PLoS Pathog. 2021 Apr 15;17(4):e1009506. (PMID: 33857259)
J Virol. 2021 Apr 12;95(9):. (PMID: 33563656)
Virol J. 2022 Jan 31;19(1):23. (PMID: 35101046)
BMC Cancer. 2008 Aug 16;8:242. (PMID: 18706101)
J Neuroimmunol. 2018 Oct 15;323:78-86. (PMID: 30196838)
Virol Sin. 2019 Jun;34(3):315-323. (PMID: 30915606)
Emerg Microbes Infect. 2020 Dec;9(1):1748-1760. (PMID: 32691695)
Pharmacol Ther. 2011 May;130(2):157-76. (PMID: 21277893)
Signal Transduct Target Ther. 2022 Feb 21;7(1):49. (PMID: 35185151)
Fish Shellfish Immunol. 2017 Apr;63:245-254. (PMID: 28232195)
Clin Infect Dis. 2022 Aug 24;75(1):e1128-e1136. (PMID: 34423834)
Nat Commun. 2015 Apr 14;6:6656. (PMID: 25871545)
Acta Pharmacol Sin. 2005 Sep;26(9):1063-8. (PMID: 16115372)
Nature. 2013 Mar 14;495(7440):251-4. (PMID: 23486063)
Anim Cells Syst (Seoul). 2019 Dec 28;24(1):60-68. (PMID: 32158617)
Biochem Pharmacol. 2005 Nov 15;70(10):1443-57. (PMID: 16181613)
J Tradit Complement Med. 2022 Jan;12(1):69-72. (PMID: 34545325)
Planta Med. 2018 Nov;84(16):1151-1164. (PMID: 29925102)
Pathogens. 2021 Feb 20;10(2):. (PMID: 33672588)
Nat Commun. 2021 Jan 12;12(1):279. (PMID: 33436624)
Eur J Drug Metab Pharmacokinet. 2016 Oct;41(5):587-94. (PMID: 25956504)
PLoS One. 2011 Apr 29;6(4):e18490. (PMID: 21559510)
EMBO Rep. 2009 Dec;10(12):1314-9. (PMID: 19893576)
Oxid Med Cell Longev. 2018 Feb 20;2018:3159801. (PMID: 29675132)
Clin Infect Dis. 2022 Aug 24;75(1):e44-e49. (PMID: 35271728)
Pharmaceuticals (Basel). 2021 Aug 31;14(9):. (PMID: 34577585)
J Immunol. 2007 Jul 15;179(2):753-63. (PMID: 17617564)
ACS Chem Neurosci. 2018 Dec 19;9(12):3108-3116. (PMID: 29989791)
Nat Microbiol. 2020 Apr;5(4):536-544. (PMID: 32123347)
Lancet. 2020 Feb 15;395(10223):497-506. (PMID: 31986264)
Viruses. 2015 Sep 10;7(9):4894-910. (PMID: 26378567)
Curr Mol Med. 2012 Dec;12(10):1244-52. (PMID: 22834827)
Int J Mol Med. 2019 May;43(5):1969-1978. (PMID: 30864681)
Nature. 2021 Nov;599(7883):114-119. (PMID: 34488225)
PLoS Biol. 2019 Jan 10;17(1):e3000107. (PMID: 30629605)
Mol Med Rep. 2018 Feb;17(2):2719-2723. (PMID: 29207060)
Antimicrob Agents Chemother. 2020 Jul 22;64(8):. (PMID: 32513797)
Liver Int. 2012 Jul;32(6):989-97. (PMID: 22098176)
Nutr J. 2008 Apr 21;7:11. (PMID: 18426577)
فهرسة مساهمة: Keywords: MERS-CoV; SARS-CoV; SARS-CoV-2; antiviral agents; coronaviruses; honokiol; inhibitor
المشرفين على المادة: 11513CCO0N (honokiol)
0 (Antiviral Agents)
SCR Organism: SARS-CoV-2 variants
تواريخ الأحداث: Date Created: 20230522 Date Completed: 20230619 Latest Revision: 20231120
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC10269499
DOI: 10.1128/spectrum.03273-22
PMID: 37212560
قاعدة البيانات: MEDLINE
الوصف
تدمد:2165-0497
DOI:10.1128/spectrum.03273-22