Skip to main content

Advertisement

SpringerLink
Log in

In Silico Design and Experimental Validation of Novel Oxazole Derivatives Against Varicella zoster virus

  • Original Paper
  • Published:
Molecular Biotechnology Aims and scope Submit manuscript

Abstract

Varicella zoster virus (VZV) infection causes severe disease such as chickenpox, shingles, and postherpetic neuralgia, often leading to disability. Reactivation of latent VZV is associated with a decrease in specific cellular immunity in the elderly and in patients with immunodeficiency. However, due to the limited efficacy of existing therapy and the emergence of antiviral resistance, it has become necessary to develop new and effective antiviral drugs for the treatment of diseases caused by VZV, particularly in the setting of opportunistic infections. The goal of this work is to identify potent oxazole derivatives as anti-VZV agents by machine learning, followed by their synthesis and experimental validation. Predictive QSAR models were developed using the Online Chemical Modeling Environment (OCHEM). Data on compounds exhibiting antiviral activity were collected from the ChEMBL and uploaded in the OCHEM database. The predictive ability of the models was tested by cross-validation, giving coefficient of determination q2 = 0.87–0.9. The validation of the models using an external test set proves that the models can be used to predict the antiviral activity of newly designed and known compounds with reasonable accuracy within the applicability domain (q2 = 0.83–0.84). The models were applied to screen a virtual chemical library with expected activity of compounds against VZV. The 7 most promising oxazole derivatives were identified, synthesized, and tested. Two of them showed activity against the VZV Ellen strain upon primary in vitro antiviral screening. The synthesized compounds may represent an interesting starting point for further development of the oxazole derivatives against VZV. The developed models are available online at OCHEM http://ochem.eu/article/145978 and can be used to virtually screen for potential compounds with anti-VZV activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Scheme 1
Scheme 2
Fig. 3

Similar content being viewed by others

Data Availability

The data used in this work and developed models are freely available online at OCHEM https://ochem.eu/article/145978

References

  1. Johnson, R. W. (2010). Herpes zoster and postherpetic neuralgia. Expert Review of Vaccines, 9(3), 21–26. https://doi.org/10.1586/erv.10.30

    Article  PubMed  Google Scholar 

  2. Floß, N., & Dolff, S. (2019). Opportunistische Infektionen durch humane Herpesviren [Opportunistic infections by human herpes viruses]. Der Internist, 60(7), 678–683. https://doi.org/10.1007/s00108-019-0615-6

    Article  PubMed  Google Scholar 

  3. Andrei, G., & Snoeck, R. (2021). Advances and perspectives in the management of Varicella-Zoster Virus infections. Molecules, 26(4), 1132. https://doi.org/10.3390/molecules26041132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kaplan, J. E., Benson, C., Holmes, K. K., Brooks, J. T., Pau, A., & Masur, H., Centers for Disease Control and Prevention (CDC), National Institutes of Health, & HIV Medicine Association of the Infectious Diseases Society of America. (2009). Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports, 58(RR-4), 1–207.

    Google Scholar 

  5. Panggabean, J. A., Adiguna, S. P., Rahmawati, S. I., Ahmadi, P., Zainuddin, E. N., Bayu, A., & Putra, M. Y. (2022). Antiviral activities of algal-based sulfated polysaccharides. Molecules, 27, 1178. https://doi.org/10.3390/molecules27041178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Lau, Z. L., Low, S. S., Ezeigwe, E. R., Chew, K. W., Chai, W. S., Bhatnagar, A., Yap, Y. J., & Show, P. L. (2022). A review on the diverse interactions between microalgae and nanomaterials: Growth variation, photosynthetic performance and toxicity. Bioresource technology, 351, 127048. https://doi.org/10.1016/j.biortech.2022.127048

    Article  CAS  PubMed  Google Scholar 

  7. Costa, J. A. V., Moreira, J. B., Fanka, L. S., da Kosinski, R. C., & de Morais, M. G. (2020). Microalgal biotechnology applied in biomedicine. In O. Konur (Ed.), Handbook of algal science technology and medicine (pp. 429–439). Elsevier.

    Chapter  Google Scholar 

  8. Chan, S. S., Low, S. S., Chew, K. W., Ling, T. C., Rinklebe, J., Juan, J. C., Ng, E. P., & Show, P. L. (2022). Prospects and environmental sustainability of phyconanotechnology: A review on algae-mediated metal nanoparticles synthesis and mechanism. Environmental research, 212(pt A), 113140. https://doi.org/10.1016/j.envres.2022.113140

    Article  CAS  PubMed  Google Scholar 

  9. Huleihel, M., Ishanu, V., Tal, J., & Arad, S. (2001). Antiviral effect of red microalgal polysaccharides on herpes simplex and Varicella zoster viruses. Journal of applied phycology, 13, 127–134.

    Article  CAS  Google Scholar 

  10. Lanh, P. T., Nguyen, H. M., Duong, B. T. T., Hoa, N. T., Thom, L. T., Tam, L. T., Thu, H. T., Nha, V. V., Hong, D. D., Mouradov, A., Koyande, A. K., Show, P.-L., & Van Quyen, D. (2021). Generation of microalga chlamydomonas reinhardtii expressing Vp28 protein as oral vaccine candidate for shrimps against White Spot Syndrome Virus (wssv) infection. Aquaculture, 540, 736737. https://doi.org/10.1016/j.aquaculture.2021.736737

    Article  CAS  Google Scholar 

  11. Kozlovskaya, L. I., Andrei, G., Orlov, A. A., Khvatov, E. V., Koruchekov, A. A., Belyaev, E. S., Nikolaev, E. N., Korshun, V. A., Snoeck, R., Osolodkin, D. I., Matyugina, E. S., & Aralov, A. V. (2019). Antiviral activity spectrum of phenoxazine nucleoside derivatives. Antiviral research, 163, 117–124. https://doi.org/10.1016/j.antiviral.2019.01.010

    Article  CAS  PubMed  Google Scholar 

  12. Liu, C., Chen, Q., Yang, M., & Schneller, S. W. (2013). C-3 halo and 3-methyl substituted 5’-nor-3-deazaaristeromycins: Synthesis and antiviral properties. Bioorganic & medicinal chemistry, 21(1), 359–364. https://doi.org/10.1016/j.bmc.2012.09.051

    Article  CAS  Google Scholar 

  13. Baszczyňski, O., Kaiser, M. M., Česnek, M., Břehová, P., Jansa, P., Procházková, E., Dračínský, M., Snoeck, R., Andrei, G., & Janeba, Z. (2018). Xanthine-based acyclic nucleoside phosphonates with potent antiviral activity against varicella-zoster virus and human cytomegalovirus. Antiviral chemistry & chemotherapy, 26, 2040206618813050. https://doi.org/10.1177/2040206618813050

    Article  CAS  Google Scholar 

  14. Wang, M., Srivastava, P., Liu, C., Snoeck, R., Andrei, G., De Jonghe, S., & Herdewijn, P. (2018). Synthesis and antiviral evaluation of cyclopentyl nucleoside phosphonates. European journal of medicinal chemistry, 150, 616–625. https://doi.org/10.1016/j.ejmech.2018.03.008

    Article  CAS  PubMed  Google Scholar 

  15. Musella, S., di Sarno, V., Ciaglia, T., Sala, M., Spensiero, A., Scala, M. C., Ostacolo, C., Andrei, G., Balzarini, J., Snoeck, R., Novellino, E., Campiglia, P., Bertamino, A., & Gomez-Monterrey, I. M. (2016). Identification of an indol-based derivative as potent and selective Varicella Zoster Virus (VZV) inhibitor. European journal of medicinal chemistry, 124, 773–781. https://doi.org/10.1016/j.ejmech.2016.09.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Metelytsia, L. O., Trush, M. M., Kovalishyn, V. V., Hodyna, D. M., Kachaeva, M. V., Brovarets, V. S., Pilyo, S. G., Sukhoveev, V. V., Tsyhankov, S. A., Blagodatnyi, V. M., & Semenyuta, I. V. (2021). 1,3-Oxazole derivatives of cytisine as potential inhibitors of glutathione reductase of Candida spp.: QSAR modeling, docking analysis and experimental study of new anti-Candida agents. Computational biology and chemistry, 90, 107407. https://doi.org/10.1016/j.compbiolchem.2020.107407

    Article  CAS  PubMed  Google Scholar 

  17. Semenyuta, I., Kovalishyn, V., Tanchuk, V., Pilyo, S., Zyabrev, V., Blagodatnyy, V., Trokhimenko, O., Brovarets, V., & Metelytsia, L. (2016). 1,3-Oxazole derivatives as potential anticancer agents: Computer modeling and experimental study. Computational biology and chemistry, 65, 8–15. https://doi.org/10.1016/j.compbiolchem.2016.09.012

    Article  CAS  PubMed  Google Scholar 

  18. Swellmeen, L. (2016). 1,3-oxazole derivatives: A review of biological activities as antipathogenic. Der Pharma Chemica, 8, 269–286.

    CAS  Google Scholar 

  19. Kovalishyn, V., Zyabrev, V., Kachaeva, M., Ziabrev, K., Keith, K., Harden, E., Hartline, C., James, S. H., & Brovarets, V. (2021). Design of new imidazole derivatives with anti-HCMV activity: QSAR modeling, synthesis and biological testing. Journal of computer-aided molecular design, 35(12), 1177–1187. https://doi.org/10.1007/s10822-021-00428-z

    Article  CAS  PubMed  Google Scholar 

  20. Kovalishyn, V., Grouleff, J., Semenyuta, I., Sinenko, V. O., Slivchuk, S. R., Hodyna, D., Brovarets, V., Blagodatny, V., Poda, G., Tetko, I. V., & Metelytsia, L. (2018). Rational design of isonicotinic acid hydrazide derivatives with antitubercular activity: Machine learning, molecular docking, synthesis and biological testing. Chemical biology & drug design, 92(1), 1272–1278. https://doi.org/10.1111/cbdd.13188

    Article  CAS  Google Scholar 

  21. Kachaeva, M. V., Pilyo, S. G., Hartline, C. B., Harden, E. A., Prichard, M. N., Zhirnov, V. V., & Brovarets, V. S. (2019). In vitro activity of novel derivatives of 1,3-oxazole-4-carboxylate and 1,3-oxazole-4-carbonitrile against human cytomegalovirus. Medicinal chemistry research, 28, 1205–1211. https://doi.org/10.1007/s00044-019-02365-x

    Article  CAS  Google Scholar 

  22. Abdurakhmanova, E. R., Brusnakov, M. Y., Golovchenko, O. V., Pilyo, S. G., Velychko, N. V., Harden, E. A., Prichard, M. N., James, S. H., Zhirnov, V. V., & Brovarets, V. S. (2020). Synthesis and in vitro anticytomegalovirus activity of 5-hydroxyalkylamino-1,3-oxazoles derivatives. Medicinal chemistry research., 29, 1669–1675. https://doi.org/10.1007/s00044-020-02593-6

    Article  CAS  Google Scholar 

  23. Sushko, I., Novotarskyi, S., Körner, R., et al. (2011). Online chemical modeling environment (OCHEM): Web platform for data storage, model development and publishing of chemical information. Journal of computer-aided molecular design, 25(6), 533–554. https://doi.org/10.1007/s10822-011-9440-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Karpov, P., Godin, G., & Tetko, I. V. (2020). Transformer-CNN: Swiss knife for QSAR modeling and interpretation. Journal of cheminformatics, 12(1), 17. https://doi.org/10.1186/s13321-020-00423-w

    Article  PubMed  PubMed Central  Google Scholar 

  25. Tetko, I. V., Karpov, P., Bruno, E., Kimber, T. B., & Godin, G. (2019). Augmentation Is What You Need! In I. Tetko, V. Kůrková, P. Karpov, & F. Theis (Eds.), Lecture notes in computer science (pp. 831–835). Springer. https://doi.org/10.1007/978-3-030-30493-5_79

    Chapter  Google Scholar 

  26. Tetko, I. V., Sushko, I., Pandey, A. K., Zhu, H., Tropsha, A., Papa, E., Oberg, T., Todeschini, R., Fourches, D., & Varnek, A. (2008). Critical assessment of QSAR models of environmental toxicity against Tetrahymena pyriformis: Focusing on applicability domain and overfitting by variable selection. Journal of chemical information and modeling, 48(9), 1733–1746. https://doi.org/10.1021/ci800151m

    Article  CAS  PubMed  Google Scholar 

  27. Jonhos, N. N., & Leone, F. G. (1977). Statistic and experimental design in engineering and the physical sciences. John Wiley & Sons.

    Google Scholar 

  28. Sushko, I., Novotarskyi, S., Körner, R., Pandey, A. K., Kovalishyn, V. V., Prokopenko, V. V., & Tetko, I. V. (2010). Applicability domain for in silico models to achieve accuracy of experimental measurements. Journal of chemometrics, 24, 202–208. https://doi.org/10.1002/cem.1296

    Article  CAS  Google Scholar 

  29. Hartline, C. B., Keith, K. A., Eagar, J., Harden, E. A., Bowlin, T. L., & Prichard, M. N. (2018). A standardized approach to the evaluation of antivirals against DNA viruses: orthopox-, adeno-, and herpesviruses. Antiviral research, 159, 104–112. https://doi.org/10.1016/j.antiviral.2018.09.015

    Article  CAS  PubMed  Google Scholar 

  30. Hochscherf, J., Lindenblatt, D., Witulski, B., Birus, R., Aichele, D., Marminon, C., Bouaziz, Z., Le Borgne, M., Jose, J., & Niefind, K. (2017). Unexpected binding mode of a potent indeno[1,2-b]indole-type inhibitor of protein kinase CK2 revealed by complex structures with the catalytic subunit CK2α and Its paralog CK2α’. Pharmaceuticals (Basel, Switzerland), 10(4), 98. https://doi.org/10.3390/ph10040098

    Article  CAS  PubMed  Google Scholar 

  31. Brown, N. R., Korolchuk, S., Martin, M. P., Stanley, W. A., Moukhametzianov, R., Noble, M., & Endicott, J. A. (2015). CDK1 structures reveal conserved and unique features of the essential cell cycle CDK. Nature communications, 6, 6769. https://doi.org/10.1038/ncomms7769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Mapelli, M., Massimiliano, L., Crovace, C., Seeliger, M. A., Tsai, L. H., Meijer, L., & Musacchio, A. (2005). Mechanism of CDK5/p25 binding by CDK inhibitors. Journal of medicinal chemistry, 48(3), 671–679. https://doi.org/10.1021/jm049323m

    Article  CAS  PubMed  Google Scholar 

  33. Berman, H. M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T. N., Weissig, H., Shindyalov, I. N., & Bourne, P. E. (2000). The protein data bank. Nucleic acids research, 28(1), 235–242. https://doi.org/10.1093/nar/28.1.235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Trott, O., & Olson, A. J. (2010). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of computational chemistry, 31(2), 455–461. https://doi.org/10.1002/jcc.21334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Sanner, M. F. (1999). Python: A programming language for software integration and development. Journal of molecular graphics & modelling, 17(1), 57–61.

    CAS  Google Scholar 

  36. Sushko, I., Salmina, E., Potemkin, V. A., Poda, G., & Tetko, I. V. (2012). ToxAlerts: A web server of structural alerts for toxic chemicals and compounds with potential adverse reactions. Journal of chemical information and modeling, 52(8), 2310–2316. https://doi.org/10.1021/ci300245q

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Babii, S. B., Zyabrev, V. S., & Drach, B. S. (2001). Conversion of N-(1-Arylsulfonyl-2,2-dichloroethenyl)carboxamides into derivatives of 4,5-Dimercaptooxazole. Russian journal of organic chemistry, 37, 1149–1152. https://doi.org/10.1023/A:1013196415680

    Article  CAS  Google Scholar 

  38. Kachaeva, M. V., Hodyna, D. M., Obernikhina, N. V., Pilyo, S. G., Kovalenko, Y. S., Prokopenko, V. M., Kachkovsky, O. D., & Brovarets, V. S. (2019). Design, synthesis and evaluation of novel sulfonamides as potential anticancer agents. Journal of heterocyclic chemistry, 56, 3122–3134. https://doi.org/10.1016/j.compbiolchem.2018.04.006

    Article  CAS  Google Scholar 

  39. Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2001). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced drug delivery reviews, 46(1–3), 3–26. https://doi.org/10.1016/s0169-409x(00)00129-0

    Article  CAS  PubMed  Google Scholar 

  40. Pires, D. E., Blundell, T. L., & Ascher, D. B. (2015). pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. Journal of medicinal chemistry, 58(9), 4066–4072. https://doi.org/10.1021/acs.jmedchem.5b00104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Andrei, G., & Snoeck, R. (2013). Advances in the treatment of varicella-zoster virus infections. Advances in pharmacology, 67, 107–168. https://doi.org/10.1016/B978-0-12-405880-4.00004-4

    Article  CAS  PubMed  Google Scholar 

  42. De, S. K., Hart, J. C., & Breuer, J. (2015). Herpes simplex virus and varicella zoster virus: Recent advances in therapy. Current opinion in infectious diseases, 28(6), 589–595. https://doi.org/10.1097/QCO.0000000000000211

    Article  CAS  PubMed  Google Scholar 

  43. Qiu, X., Janson, C. A., Culp, J. S., Richardson, S. B., Debouck, C., Smith, W. W., & Abdel-Meguid, S. S. (1997). Crystal structure of varicella-zoster virus protease. Proceedings of the National Academy of Sciences of the United States of America, 94(7), 2874–2879. https://doi.org/10.1073/pnas.94.7.2874

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Leisenfelder, S. A., & Moffat, J. F. (2006). Varicella-zoster virus infection of human foreskin fibroblast cells results in atypical cyclin expression and cyclin-dependent kinase activity. Journal of virology, 80(11), 5577–5587. https://doi.org/10.1128/JVI.00163-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Habran, L., Bontems, S., Di Valentin, E., Sadzot-Delvaux, C., & Piette, J. (2005). Varicella-zoster virus IE63 protein phosphorylation by roscovitine-sensitive cyclin-dependent kinases modulates its cellular localization and activity. The Journal of biological chemistry, 280(32), 29135–29143. https://doi.org/10.1074/jbc.M503312200

    Article  CAS  PubMed  Google Scholar 

  46. Bontems, S., Di Valentin, E., Baudoux, L., Rentier, B., Sadzot-Delvaux, C., & Piette, J. (2002). Phosphorylation of varicella-zoster virus IE63 protein by casein kinases influences its cellular localization and gene regulation activity. The Journal of biological chemistry, 277(23), 21050–21060. https://doi.org/10.1074/jbc.M111872200

    Article  CAS  PubMed  Google Scholar 

  47. Leisenfelder, S. A., Kinchington, P. R., & Moffat, J. F. (2008). Cyclin-dependent kinase 1/cyclin B1 phosphorylates varicella-zoster virus IE62 and is incorporated into virions. Journal of virology, 82(24), 12116–12125. https://doi.org/10.1128/JVI.00153-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Grose, C., Jackson, W., & Traugh, J. A. (1989). Phosphorylation of varicella-zoster virus glycoprotein gpI by mammalian casein kinase II and casein kinase I. Journal of virology, 63(9), 3912–3918. https://doi.org/10.1128/JVI.63.9.3912-3918.1989

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Ye, M., Duus, K. M., Peng, J., Price, D. H., & Grose, C. (1999). Varicella-zoster virus Fc receptor component gI is phosphorylated on its endodomain by a cyclin-dependent kinase. Journal of virology, 73(2), 1320–1330. https://doi.org/10.1128/JVI.73.2.1320-1330.1999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Olson, J. K., Bishop, G. A., & Grose, C. (1997). Varicella-zoster virus Fc receptor gE glycoprotein: Serine/threonine and tyrosine phosphorylation of monomeric and dimeric forms. Journal of virology, 71(1), 110–119. https://doi.org/10.1128/JVI.71.1.110-119.1997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Taylor, S. L., Kinchington, P. R., Brooks, A., & Moffat, J. F. (2004). Roscovitine, a cyclin-dependent kinase inhibitor, prevents replication of varicella-zoster virus. Journal of virology, 78(6), 2853–2862. https://doi.org/10.1128/jvi.78.6.2853-2862.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

These studies were funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN75N93019D00016 (SHJ). This work was also supported by the National Research Foundation of Ukraine (Grant number 2020.01/0075) and by the NAS of Ukraine.

Author information

Authors and Affiliations

  1. V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Science of Ukraine, Kyiv, 02094, Ukraine

    Vasyl Kovalishyn, Oleksandr Severin, Maryna Kachaeva, Oleksandr Kobzar, Andriy Vovk & Volodymyr Brovarets

  2. Department of Pediatrics, Division of Pediatric Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, 35233, USA

    Kathy A. Keith, Emma A. Harden, Caroll B. Hartline & Scott H. James

Authors
  1. Vasyl Kovalishyn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Oleksandr Severin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maryna Kachaeva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Oleksandr Kobzar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kathy A. Keith
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Emma A. Harden
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Caroll B. Hartline
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Scott H. James
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Andriy Vovk
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Volodymyr Brovarets
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vasyl Kovalishyn.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest to declare that are relevant to the content of this article.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 4540 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kovalishyn, V., Severin, O., Kachaeva, M. et al. In Silico Design and Experimental Validation of Novel Oxazole Derivatives Against Varicella zoster virus. Mol Biotechnol 66, 707–717 (2024). https://doi.org/10.1007/s12033-023-00670-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12033-023-00670-w

Keywords

Search

Navigation