Razavi Journal of Medicine

Razavi Journal of Medicine

Prophylactic effects of colchicine against COVID-19 in patients with Behcet’s disease

Articles in Press

Document Type : Original Article

Authors
Mansour Salesi
Behrokh Shojaie
Division of Rheumatology, Department of Internal Medicine, School of Medicine, Isfahan, Iran.
10.30483/rjm.2026.254663.1435
Abstract
Background: Behçet's disease (BD) is a multisystemic vasculitis that is treated with colchicine. Based on observations, the number of patients with COVID-19 in the BD patient population is low, and the severity of COVID-19 is also very low. Such observations led to the hypothesis that colchicine can reduce the occurrence and severity of COVID-19 in patients with BD.

Objectives: This study aimed to investigate the effects of colchicine in preventing COVID-19 or reducing the severity of the disease in patients with BD, emphasizing the identification of the target proteins of colchicine.

Methods: According to a retrospective case-control study, the frequency of patients with COVID-19 was determined in two groups of BD patients treated with colchicine or not during the COVID-19 pandemic. Patient information was collected through telephone interviews and then subjected to statistical analysis. Also, based on in-silico studies and molecular docking, the target proteins of colchicine, which probably play a role in preventing the COVID-19, were identified.

Results: 65 qualified patients with BD participated in this study. Among them, 44 were women and 21 were men. In this population, only 40% of patients, including 20 women and 6 men, had experienced COVID-19. Also, only 27.7 percent of this population (11 women and 7 men) were treated with colchicine, and the majority of the population (72.3 %) was not under treatment with colchicine at the start of the COVID-19 pandemic. Based on the in-silico results, one hundred proteins were introduced as colchicine targets and it was shown that colchicine can effectively interact with some proteins such as Tubulin beta-1 chain, Histone deacetylases 6,1,3, ADAM17, E-selectin and angiotensin-converting enzyme 2.

Conclusion: Inhibiting the activity of Tubulin beta-1 chain proteins, Histone deacetylases 6,1,3, ADAM17, E-selectin, and angiotensin-converting enzyme 2 following the interaction of colchicine with these proteins can be the reason for the prophylactic effects of this drug in preventing COVID-19 or reducing the severity of the disease.
Keywords
Behcet&rsquo
s disease, Colchicine, COVID-19

Acknowledgements: We are grateful to the Isfahan University of Medical Sciences for financial support. We would also like to thank all people including patients who have participated in this study.

Conflict of Interest: The authors declare that they have no conflict of interest.

Data Availability: All data generated or analysed during this study are included in this published article.

Funding: None.

Consent to Publish: Not applicable.

Ethics approval: All the procedures performed in the studies involving human participants were in accordance with the ethical standards of the local ethics committee of Isfahan University of Medical Sciences (IR.ARI.MUI.REC.1400.069), as well as the 1964 Helsinki declaration. Written informed consent was obtained from all patients and healthy subjects.

Authors' contributions: Behrokh Shojaie and Mansour Salesi contributed to the study conception and designed the questionnaire for this study. Behrokh Shojaie and Mansour Salesi collected data. Behrokh Shojaie analyzed data and interpreted results. Behrokh Shojaie prepared, wrote and edited the manuscript. Mansour Salesi and Behrokh Shojaie critically revised the manuscript. All authors read and approved the final manuscript.

Open Access Policy: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/

1. Parasher A. COVID-19: Current understanding of its Pathophysiology, Clinical presentation and Treatment. Postgrad Med J. 2021;97(1147):312-20.
https://doi.org/10.1136/postgradmedj-2020-138577
PMid:32978337 PMCid:PMC10017004
 
2. Pourpashang P. Kawasaki-like disease associated with COVID-19 (Kawa-COVID-19); an overview of recent evident. Journal of Preventive Epidemiology. 2025;11(1):e39274-e.
https://doi.org/10.34172/jpe.2025.39274  
 
3. Nokhostin F, Dargahi MM, Tutunchi S, Rezaeeyan H. Evaluation of prognostic/diagnostic value of Hematological markers in the detection of inflammation in coronavirus disease: a review study. 2020.
https://doi.org/10.30699/jambs.28.128.171  
 
4. McElvaney OJ, McEvoy NL, McElvaney OF, Carroll TP, Murphy MP, Dunlea DM, et al. Characterization of the Inflammatory Response to Severe COVID-19 Illness. Am J Respir Crit Care Med. 2020;202(6):812-21.
https://doi.org/10.1164/rccm.202005-1583OC
PMid:32584597 PMCid:PMC7491404  
 
5. Subkhan M, Malikul Mulki T, Ambar NS, Irfana L, Widyaningsih S, Permana PBD, et al. Low platelet counts and monocytosis were associated with reduced risk of severe COVID-19 manifestation: a single-center study from Indonesia. Immunopathol Persa. 2025;11(2):e40595-e.
https://doi.org/10.34172/ipp.2025.40595  
 
6. Rizk JG, Kalantar-Zadeh K, Mehra MR, Lavie CJ, Rizk Y, Forthal DN. Pharmaco-Immunomodulatory Therapy in COVID-19. Drugs. 2020;80(13):1267-92.
https://doi.org/10.1007/s40265-020-01367-z
PMid:32696108  
 
7. Reyes AZ, Hu KA, Teperman J, Wampler Muskardin TL, Tardif JC, Shah B, et al. Anti-inflammatory therapy for COVID-19 infection: the case for colchicine. Ann Rheum Dis. 2021;80(5):550-7.
https://doi.org/10.1136/annrheumdis-2020-219174
PMid:33293273 PMCid:PMC8491433  
 
8. Slobodnick A, Shah B, Krasnokutsky S, Pillinger MH. Update on colchicine, 2017. Rheumatology (Oxford). 2018;57(suppl_1):i4-i11.
https://doi.org/10.1093/rheumatology/kex453
PMid:29272515 PMCid:PMC5850858  
 
9. Fiolet ATL, Opstal TSJ, Mosterd A, Eikelboom JW, Jolly SS, Keech AC, et al. Efficacy and safety of low-dose colchicine in patients with coronary disease: a systematic review and meta-analysis of randomized trials. Eur Heart J. 2021;42(28):2765-75.
https://doi.org/10.1093/eurheartj/ehab115
PMid:33769515  
 
10. Imazio M, Brucato A, Adler Y. A randomized trial of colchicine for acute pericarditis. N Engl J Med. 2014;370(8):781.
https://doi.org/10.1056/NEJMc1315351  
 
11. Nuki G. Colchicine: its mechanism of action and efficacy in crystal-induced inflammation. Curr Rheumatol Rep. 2008;10(3):218-27.
https://doi.org/10.1007/s11926-008-0036-3
PMid:18638431  
 
12. Martínez GJ, Celermajer DS, Patel S. The NLRP3 inflammasome and the emerging role of colchicine to inhibit atherosclerosis-associated inflammation. Atherosclerosis. 2018;269:262-71.
https://doi.org/10.1016/j.atherosclerosis.2017.12.027
PMid:29352570  
 
13. Freeman TL, Swartz TH. Targeting the NLRP3 Inflammasome in Severe COVID-19. Front Immunol. 2020;11:1518.
https://doi.org/10.3389/fimmu.2020.01518
PMid:32655582  
 
14. Lopes MI, Bonjorno LP, Giannini MC, Amaral NB, Menezes PI, Dib SM, et al. Beneficial effects of colchicine for moderate to severe COVID-19: a randomised, double-blinded, placebo-controlled clinical trial. RMD Open. 2021;7(1).
https://doi.org/10.1136/rmdopen-2020-001455
PMid:33542047 PMCid:PMC7868202  
 
15. Deftereos SG, Giannopoulos G, Vrachatis DA, Siasos GD, Giotaki SG, Gargalianos P, et al. Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019: The GRECCO-19 Randomized Clinical Trial. JAMA Netw Open. 2020;3(6):e2013136.
https://doi.org/10.1001/jamanetworkopen.2020.13136
PMid:32579195 PMCid:PMC7315286  
 
16. Yasmin F, Najeeb H, Moeed A, Hassan W, Khatri M, Asghar MS, et al. Safety and efficacy of colchicine in COVID-19 patients: A systematic review and meta-analysis of randomized control trials. PLOS ONE. 2022;17(4):e0266245.
https://doi.org/10.1371/journal.pone.0266245
PMid:35381033 PMCid:PMC8982874  
 
17. Bonaventura A, Vecchié A, Dagna L, Tangianu F, Abbate A, Dentali F. Colchicine for COVID-19: targeting NLRP3 inflammasome to blunt hyperinflammation. Inflammation Research. 2022;71(3):293-307.
https://doi.org/10.1007/s00011-022-01540-y
PMid:35113170 PMCid:PMC8811745  
 
18. Yazici H, Seyahi E, Hatemi G, Yazici Y. Behçet syndrome: a contemporary view. Nat Rev Rheumatol. 2018;14(2):107-19.
https://doi.org/10.1038/nrrheum.2018.3
https://doi.org/10.1038/nrrheum.2017.208
PMid:29296024  
 
19. Emmi G, Silvestri E, Squatrito D, D'Elios MM, Ciucciarelli L, Prisco D, et al. Behçet's syndrome pathophysiology and potential therapeutic targets. Intern Emerg Med. 2014;9(3):257-65.
https://doi.org/10.1007/s11739-013-1036-5
PMid:24415351  
 
20. Leccese P, Alpsoy E. Behçet's Disease: An Overview of Etiopathogenesis. Front Immunol. 2019;10:1067.
https://doi.org/10.3389/fimmu.2019.01067
PMid:31134098 PMCid:PMC6523006  
 
21. Tong B, Liu X, Xiao J, Su G. Immunopathogenesis of Behcet's Disease. Front Immunol. 2019;10:665.
https://doi.org/10.3389/fimmu.2019.00665
PMid:30984205 PMCid:PMC6449449  
 
22. Karadag O, Bolek EC. Management of Behcet's syndrome. Rheumatology (Oxford). 2020;59(Suppl 3):iii108-iii17.
https://doi.org/10.1093/rheumatology/keaa086
PMid:32348509  
 
23. Payne S. Virus Interactions With the Cell: Viruses. 2017:23-35. doi: 10.1016/B978-0-12-803109-4.00003-9. Epub 2017 Sep 1.
https://doi.org/10.1016/B978-0-12-803109-4.00003-9
PMCid:PMC7173567  
 
24. Sargsyan A, Sahakyan H, Nazaryan K. Effect of Colchicine Binding Site Inhibitors on the Tubulin Intersubunit Interaction. ACS Omega. 2023;8(32):29448-54.
https://doi.org/10.1021/acsomega.3c02979
PMid:37599936 PMCid:PMC10433359  
 
25. Hastie SB. Interactions of colchicine with tubulin. Pharmacol Ther. 1991;51(3):377-401.
https://doi.org/10.1016/0163-7258(91)90067-V
PMid:1792241  
 
26. Little M, Ludueña RF. Structural differences between brain beta 1- and beta 2-tubulins: implications for microtubule assembly and colchicine binding. Embo j. 1985;4(1):51-6.
https://doi.org/10.1002/j.1460-2075.1985.tb02316.x
PMid:4018027 PMCid:PMC554150  
 
27. Goodson HV, Jonasson EM. Microtubules and Microtubule-Associated Proteins. Cold Spring Harb Perspect Biol. 2018;10(6).
https://doi.org/10.1101/cshperspect.a022608
PMid:29858272 PMCid:PMC5983186  
 
28. Aminpour M, Hameroff S, Tuszynski JA. How COVID-19 Hijacks the Cytoskeleton: Therapeutic Implications. Life. 2022;12(6):814.
https://doi.org/10.3390/life12060814
PMid:35743845 PMCid:PMC9225596  
 
29. Jackson CB, Farzan M, Chen B, Choe H. Mechanisms of SARS-CoV-2 entry into cells. Nat Rev Mol Cell Biol. 2022;23(1):3-20.
https://doi.org/10.1038/s41580-021-00418-x
PMid:34611326 PMCid:PMC8491763  
 
30. Seto E, Yoshida M. Erasers of histone acetylation: the histone deacetylase enzymes. Cold Spring Harb Perspect Biol. 2014;6(4):a018713.
https://doi.org/10.1101/cshperspect.a018713
PMid:24691964 PMCid:PMC3970420  
 
31. Takahashi Y, Hayakawa A, Sano R, Fukuda H, Harada M, Kubo R, et al. Histone deacetylase inhibitors suppress ACE2 and ABO simultaneously, suggesting a preventive potential against COVID-19. Scientific Reports. 2021;11(1):3379.
https://doi.org/10.1038/s41598-021-82970-2
PMid:33564039 PMCid:PMC7873266  
 
32. Ripamonti C, Spadotto V, Pozzi P, Stevenazzi A, Vergani B, Marchini M, et al. HDAC Inhibition as Potential Therapeutic Strategy to Restore the Deregulated Immune Response in Severe COVID-19. Front Immunol. 2022;13:841716.
https://doi.org/10.3389/fimmu.2022.841716
PMid:35592335 PMCid:PMC9111747  
 
33. Buran K. Colchicine as a potential HDAC inhibitor: comparative binding energies and prospects for cancer therapy repurposing. Journal of Research in Pharmacy. 2024;28(5):8.
https://doi.org/10.29228/jrp.853  
 
34. Zhang X, Kong Y, Zhang J, Su M, Zhou Y, Zang Y, et al. Design, synthesis and biological evaluation of colchicine derivatives as novel tubulin and histone deacetylase dual inhibitors. European Journal of Medicinal Chemistry. 2015;95:127-35.
https://doi.org/10.1016/j.ejmech.2015.03.035
PMid:25805446  
 
35. Jocher G, Grass V, Tschirner SK, Riepler L, Breimann S, Kaya T, et al. ADAM10 and ADAM17 promote SARS-CoV-2 cell entry and spike protein-mediated lung cell fusion. EMBO Rep. 2022;23(6):e54305.
https://doi.org/10.15252/embr.202154305
PMid:35527514 PMCid:PMC9171409  
 
36. Zipeto D, Palmeira JDF, Argañaraz GA, Argañaraz ER. ACE2/ADAM17/TMPRSS2 Interplay May Be the Main Risk Factor for COVID-19. Front Immunol. 2020;11:576745.
https://doi.org/10.3389/fimmu.2020.576745
PMid:33117379 PMCid:PMC7575774  
 
37. Parra-Medina R, Sarmiento-Monroy JC, Rojas-Villarraga A, Garavito E, Montealegre-Gómez G, Gómez-López A. Colchicine as a possible therapeutic option in COVID-19 infection. Clin Rheumatol. 2020;39(8):2485-6.
https://doi.org/10.1007/s10067-020-05247-5
PMid:32556936 PMCid:PMC7301347  
 
38. Beyerstedt S, Casaro EB, Rangel É B. COVID-19: angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection. Eur J Clin Microbiol Infect Dis. 2021;40(5):905-19.
https://doi.org/10.1007/s10096-020-04138-6
PMid:33389262  
 
39. Abd Al-Hameed JM, Ali BH. Evaluation of ERK-5 expression in type 2 diabetic patients following COVID-19 vaccination; a prospective case-control study. Journal of Renal Injury Prevention. 2026;15(3).  
 
 
Razavi Journal of Medicine

Articles in Press, Accepted Manuscript
Available Online from 20 September 2026