vestimИзвестия Национальной академии наук Беларуси. Серия медицинских наукProceedings of the National Academy of Sciences of Belarus, Medical series1814-60232524-2350The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1814-6023-2024-21-2-104-115vestim-963Research ArticleКЛИНИЧЕСКАЯ И ЭКСПЕРИМЕНТАЛЬНАЯ МЕДИЦИНАCLINICAL AND EXPERIMENTAL MEDICINEНовый подход к разработке вакцины от кариеса зубовA new approach in the development of a dental caries vaccineРубниковичС. П.RubnikovichS. P.

Рубникович Сергей Петрович – член-корреспондент, д-р мед. наук, профессор, ректор

пр. Дзержинского, 83, 220116, г. Минск

Sergeу P. Rubnikovich – Corresponding Member, D. Sc. (Med.), Professor, Rector

83, Dzerzhinski Ave., 220116, Minsk

rubnikovich@mail.ruПобойневВ. В.PoboinevV. V.

Побойнев Виктор Витольдович – ст. преподаватель

пр. Дзержинского, 83, 220116, г. Минск

Victor V. Poboinev – Senior Lecturer

83, Dzerzhinski Ave., 220116, Minsk

dremozzew@mail.ruХрусталёвВ. В.KhrustalevV. V.

Хрусталёв Владислав Викторович – д-р биол. наук, доцент, заведующий кафедрой

пр. Дзержинского, 83, 220116, г. Минск

Vladislav V. Khrustalev – D. Sc. (Biol.), Associate Professor, Head of the Department

83, Dzerzhinski Ave., 220116, Minsk

vvkhrustalev@mail.ruБелорусский государственный медицинский университетBelarusian State Medical UniversityПобойнев Виктор Витольдович – ст. преподавательBelarusian State Medical University202427052024212104115Copyright © Рубникович С.П., Побойнев В.В., Хрусталёв В.В., 20242024Рубникович С.П., Побойнев В.В., Хрусталёв В.В.Rubnikovich S.P., Poboinev V.V., Khrustalev V.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestimed.belnauka.by/jour/article/view/963

Геномы бактерий Streptococcus mutans и Streptococcus sobrinus, вызывающих кариес зубов, в настоящее время полностью секвенированы. В то же время пространственные структуры полноразмерных поверхностных белков данных микроорганизмов, с помощью которых они прикрепляются к поверхности зубов, покрытых слюной, до сих пор инструментально не определены. Имеется ряд экспериментальных работ по использованию этих белков в процессе разработки вакцины от кариеса, однако коммерчески доступной вакцины от кариеса на данный момент нет. Для разработки эффективной и безопасной вакцины от кариеса необходимо провести целый ряд экспериментов in silico, предшествующих экспериментам in vitro, а тем более in vivo. Сегодня такой подход не только является общепризнанным, но и позволяет существенно снизить стоимость экспериментов и продолжительность времени на доклиническом и клиническом этапах.

Цель исследования – отбор антигена для последующего молекулярного моделирования уникального пептида для разработки вакцины от кариеса зубов.

По нашей гипотезе, в качестве антигена для разработки вакцины от кариеса необходимо использовать короткий фрагмент поверхностного белка (пептид) Streptococcus mutans и/или Streptococcus sobrinus, гомологичность которых по аминокислотной последовательности составляет 84,8 %. При этом пространственная структура этого пептида должна соответствовать пространственной структуре соответствующего фрагмента в полноразмерном белке. Кроме того, отобранный фрагмент белка, который войдет в состав вакцинного пептида, должен быть доступен антителам, т. е. располагаться на поверхности белка и определяться как B-клеточный линейный и пространственный эпитоп. Вакцинный пептид может состоять из наиболее стабильных фрагментов богатых аланином и пролином областей поверхностного белка Streptococcus mutans и/или Streptococcus sobrinus для взаимной стабилизации пространственной структуры.

The genomes of the bacteria Streptococcus mutans and Streptococcus sobrinus, which cause dental caries, currently have been fully sequenced. However, the secondary and tertiary structures of the full-size surface proteins of these microorganisms, by which they attach to the surface of teeth covered with saliva, have not been instrumentally determined at the moment. There are a number of experimental studies on the use of these proteins in the process of developing a dental caries vaccine. However, there is currently no commercially available dental caries vaccine.

The aim of the study was to choose an antigen for subsequent molecular modeling of a unique peptide for the development of a dental caries vaccine.

To develop an effective and safe dental caries vaccine, it is necessary to perform a number of experiments in silico, preceding experiments in vitro and in vivo. Today, this approach is not only generally recognized, but also allows to significantly reduce the cost of experiments and time at the preclinical and clinical studies. According to our hypothesis, as an antigen for the development of a dental caries vaccine, it is necessary to use a short fragment of the surface protein (a peptide) of Streptococcus mutans and/or Streptococcus sobrinus, whose homology in amino acid sequence is 84.8  %, the spatial structure of which should correspond to the spatial structure of the corresponding fragment in a full-sized protein. In addition, the selected protein fragment, which will be part of the vaccine peptide, must be available to antibodies, i. e. located on the surface of the protein and defined as a B-cell linear and spatial epitope. Also, according to our hypothesis, the vaccine peptide may consist of the most stable fragments of alanine and proline rich regions of the surface protein of Streptococcus mutans and/or Streptococcus sobrinus for mutual stabilization of the spatial structure.

кариес зубовадгезин AgI/IIантигенвакцинный пептидStreptococcus mutansStreptococcus sobrinusdental cariesadhesin AgI/IIantigenvaccine peptideStreptococcus mutansStreptococcus sobrinusReferencesСтоматология: сб. клин. протоколов: в 2 ч. / М-во здравоохранения Респ. Беларусь; под общ. ред. С. П. Рубниковича. – Минск: БГМУ, 2023. – Ч. 1. – 468 с.Rubnikovich S. P. (ed.). Dentistry: collection of clinical protocols. Pt. 1. Minsk, Belarusian State Medical University, 2023. 468 p. (in Russian).A nanoparticle-based anticaries vaccine enhances the persistent immune response to inhibit streptococcus mutans and prevent caries / Y.-B. Yu [et al.] // Microbiol. Spectr. – 2023. – Vol. 11, N 2. – P. e0432822. https://doi.org/10.1128/spectrum.04328-22Yu Y. B., Liu Y., Liang H., Dong X., Yang X. Y., Li S., Guo Z. A nanoparticle-based anticaries vaccine enhances the persistent immune response to inhibit streptococcus mutans and prevent caries. Microbiology Spectrum, 2023, vol. 11, no. 2, p. e0432822. https://doi.org/10.1128/spectrum.04328-22Human oral microbiota and its modulation for oral health / Y. Zhang [et al.] // Biomed. Pharmacother. – 2018. – Vol. 99. – P. 883–893. https://doi.org/10.1016/j.biopha.2018.01.146Zhang Y., Wang X., Li H., Ni C., Du Z., Yan F. Human oral microbiota and its modulation for oral health. Biomedicine & Pharmacotherapy, 2018, vol. 99, pp. 883–893. https://doi.org/10.1016/j.biopha.2018.01.146Smith, D. J. Dental caries vaccines: prospects and concerns / D. J. Smith // Crit. Rev. Oral Biol. Med. – 2002. – Vol. 13, N 4. – P. 335–349. https://doi.org/10.1177/154411130201300404Smith D. J. Dental caries vaccines: prospects and concerns. Critical Reviews in Oral Biology and Medicine, 2002, vol. 13, no. 4, pp. 335–349. https://doi.org/10.1177/154411130201300404Patel, M. Dental caries vaccine: are we there yet? / M. Patel // Lett. Appl. Microbiol. – 2020. – Vol. 70, N 1. – P. 2–12. https://doi.org/10.1111/lam.13218Patel M. Dental caries vaccine: are we there yet? Letters in Applied Microbiology, 2020, vol. 70, no. 1, pp. 2–12. https://doi.org/10.1111/lam.13218Forssten, S. D. Streptococcus mutans, caries and simulation models / S. D. Forssten, M. Björklund, A. C. Ouwehand // Nutrients. – 2010. – Vol. 2, N 3. – P. 290–298. https://doi.org/10.3390/nu2030290Forssten S. D., Björklund M., Ouwehand A. C. Streptococcus mutans, caries and simulation models. Nutrients, 2010, vol. 2, no. 3, pp. 290–298. https://doi.org/10.3390/nu2030290Zhang, J. S. Oral microbiome and dental caries development / J. S. Zhang, C. H. Chu, O. Y. Yu // Dent. J. (Basel). – 2022. – Vol. 10, N 10. – Art. 184. https://doi.org/10.3390/dj10100184Zhang J. S., Chu C. H., Yu O. Y. Oral microbiome and dental caries development. Dentistry Journal (Basel), 2022, vol. 10, no. 10, art. 184. https://doi.org/10.3390/dj10100184Talbman, M. A. Effects of local immunization with Streptococcus mutans on induction of salivary immunoglobulin A antibody and experimental dental caries in rats / M. A. Talbman, D. J. Smith // Infect. Immun. – 1974. – Vol. 9, N 6. – P. 1079–1091. https://doi.org/10.1128/iai.9.6.1079-1091.1974Talbman M. A., Smith D. J. Effects of local immunization with Streptococcus mutans on induction of salivary immunoglobulin A antibody and experimental dental caries in rats. Infection and Immunity, 1974, vol. 9, no. 6, pp. 1079–1091. https://doi.org/10.1128/iai.9.6.1079-1091.1974Effective immunity to dental caries: protection of gnotobiotic rats by local immunization with Streptococcus mutans / J. R. McGhee [et al.] // J. Immunol. – 1995. – Vol. 114, N 1, pt. 2. – P. 300–305. https://doi.org/10.4049/jimmunol.114.1_ part_2.300McGhee J. R., Michalek S. M., Webb J., Navia J. M., Rahman A. F., Legler D. W. Effective immunity to dental caries: protection of gnotobiotic rats by local immunization with Streptococcus mutans. Journal of Immunology, 1975, vol. 114, no. 1, pt. 2, pp. 300–305. https://doi.org/10.4049/jimmunol.114.1_part_2.300Russell, R. R. Wall-associated protein antigens of Streptococcus mutans / R. R. Russell // J. Gen. Microbiol. – 1979. – Vol. 114, N 1. – P. 109–115. https://doi.org/10.1099/00221287-114-1-109Russell R. R. Wall-associated protein antigens of Streptococcus mutans. Journal of General Microbiology, 1979, vol. 114, no. 1, pp. 109–115. https://doi.org/10.1099/00221287-114-1-109Purification and characterization of a saliva-interacting cell wall protein from Streptococcus mutans serotype f by using monoclonal antibody immunoaffinity chromatography / F. Ackermans [et al.] // Biochem. J. – 1985. – Vol. 228, N 1. – P. 211–217. https://doi.org/10.1042/bj2280211Ackermans F., Klein J. P., Ogier J., Bazin H., Cormont F., Frank R. M. Purification and characterization of a salivainteracting cell wall protein from Streptococcus mutans serotype f by using monoclonal antibody immunoaffinity chromatography. Biochemical Journal, 1985, vol. 228, no. 1, pp. 211–217. https://doi.org/10.1042/bj2280211Evidence for an immunological relationship between Streptococcus mutans and human cardiac tissue / M. Hughes [et al.] // Infect. Immun. – 1980. – Vol. 27, N 2. – P. 576–588. https://doi.org/10.1128/iai.27.2.576-588.1980Hughes M, Machardy S. M., Sheppard A. J., Woods N. C. Evidence for an immunological relationship between Streptococcus mutans and human cardiac tissue. Infection and Immunity, 1980, vol. 27, no. 2, pp. 576–588. https://doi.org/10.1128/iai.27.2.576-588.1980Comparison of Streptococcus mutans and Streptococcus sanguis receptors for human salivary agglutinin / D. R. Demuth [et al.] // Microb. Pathog. – 1990. – Vol. 9, N 3. – P. 199–211. https://doi.org/10.1016/0882-4010(90)90022-iDemuth D. R., Lammey M. S., Huck M., Lally E. T., Malamud D. Comparison of Streptococcus mutans and Streptococcus sanguis receptors for human salivary agglutinin. Microbial Pathogenesis, 1990, vol. 9, no. 3, pp. 199–211. https://doi.org/10.1016/0882-4010(90)90022-iVirulence of a spaP mutant of Streptococcus mutans in a gnotobiotic rat model / P. J. Crowley [et al.] // Infect. Immun. – 1999. – Vol. 67, N 3. – P. 1201–1206. https://doi.org/10.1128/iai.67.3.1201-1206.1999Crowley P. J., Brady L. J., Michalek S. M., Bleweis A. S. Virulence of a spaP mutant of Streptococcus mutans in a gnotobiotic rat model. Infection and Immunity, 1999, vol. 67, no. 3, pp. 1201–1206. https://doi.org/10.1128/iai.67.3.1201- 1206.1999Immunization with purified protein antigens from Streptococcus mutans against dental caries in rhesus monkeys / T. Lehner [et al.] // Infect. Immun. – 1981. – Vol. 34, N 2. – P. 407–415. https://doi.org/10.1128/iai.34.2.407-415.1981Lehner T., Russell M. W., Caldwell J., Smith R. Immunization with purified protein antigens from Streptococcus mutans against dental caries in rhesus monkeys. Infection and Immunity, 1981, vol. 34, no. 2, pp. 407–415. https://doi.org/10.1128/iai.34.2.407-415.1981Redman, T. K. Oral immunization with recombinant Salmonella typhimurium expressing surface protein antigen A (SpaA) of Streptococcus sobrinus: effects of the Salmonella virulence plasmid on the induction of protective and sustained humoral responses in rats / T. K. Redman, C. C. Harmon, S. M. Michalek // Vaccine. – 1996. – Vol. 14, N 9. – P. 868–878. https://doi.org/10.1016/0264-410x(96)00013-8Redman T. K., Harmon C. C., Michalek S. M. Oral immunization with recombinant Salmonella typhimurium expressing surface protein antigen A (SpaA) of Streptococcus sobrinus: effects of the Salmonella virulence plasmid on the induction of protective and sustained humoral responses in rats. Vaccine, 1996, vol. 14, no. 9, pp. 868–878. https://doi.org/10.1016/0264-410x(96)00013-8Immunogenicity and protective effect against oral colonization by Streptococcus mutans of synthetic peptides of a streptococcal surface protein antigen / I. Takahashi [et al.] // J. Immunol. – 1991. – Vol. 146, N 1. – P. 332–336. https://doi.org/10.4049/jimmunol.146.1.332Takahashi I., Okahashi N., Matsushita K., Tokuda M., Kanamoto T., Munekata E., Russell M. W., Koga T. Immunogenicity and protective effect against oral colonization by Streptococcus mutans of synthetic peptides of a streptococcal surface protein antigen. Journal of Immunology, 1991, vol. 146, no. 1, pp. 332–336. https://doi.org/10.4049/jimmunol.146.1.332The changing faces of Streptococcus antigen I/II polypeptide family adhesins / L. J. Brady [et al.] // Mol. Microbiol. – 2010. – Vol. 77, N 2. – P. 276–286. https://doi.org/10.1111/j.1365-2958.2010.07212.xBrady L. J., Maddocks S. E., Larson M. R. Forsgren N., Persson K., Deivanayagam C. C., Jenkinson H. F. The changing faces of Streptococcus antigen I/II polypeptide family adhesins. Molecular Microbiology, 2010, vol. 77, no. 2, pp. 276–286. https://doi.org/10.1111/j.1365-2958.2010.07212.xSaliva-binding region of Streptococcus mutans surface protein antigen / M. Nakai [et al.] // Infect. Immun. – 1993. – Vol. 61, N 10. – P. 4344–4349. https://doi.org/10.1128/iai.61.10.4344-4349.1993Nakai M., Okahashi N., Ohta H., Koga T. Saliva-binding region of Streptococcus mutans surface protein antigen. Infection and Immunity, 1993, vol. 61, no. 10, pp. 4344–4349. https://doi.org/10.1128/iai.61.10.4344-4349.1993Sequence and structural analysis of surface protein antigen I/II (SpaA) of Streptococcus sobrinus / R. J. LaPolla [et al.] // Infect. Immun. – 1991. – Vol. 59, N 8. – P. 2677–2685. https://doi.org/10.1128/iai.59.8.2677-2685.1991LaPolla R. J., Haron J. A., Kelly C. G., Taylor W. R., Bohart C., Hendricks M., Pyati J. P., Graff R. T., Ma J. K., Lehner T. Sequence and structural analysis of surface protein antigen I/II (SpaA) of Streptococcus sobrinus. Infection and Immunity, 1991, vol. 59, no. 8, pp. 2677–2685. https://doi.org/10.1128/iai.59.8.2677-2685.1991Dental caries vaccine availability: Challenges for the 21st century / A. S. M. Giasuddin [et al.] // J. Immunol. Immunother. – 2017. – Vol. 1, N 7. – Art. 100002.Giasuddin A. S. M., Huda S., Jhuma K. A., Haq A. M. Dental caries vaccine availability: Challenges for the 21st century. Journal of Immunology and Immunotherapy, 2017, vol. 1, no. 7, art. 100002.Immunochemistry of the Streptococcus mutans BHT cell membrane: Detection of determinants cross-reactive with human heart tissue / G. Y. Ayakawa [et al.] // Infect. Immun. – 1985. – Vol. 48, N 2. – P. 280–286. https://doi.org/10.1128/iai.48.2.280-286.1985Ayakawa G. Y., Siegel J. L., Crowley P. J., Bleiweis A. S. Immunochemistry of the Streptococcus mutans BHT cell membrane: detection of determinants cross-reactive with human heart tissue. Infection and Immunity, 1985, vol. 48, no. 2, pp. 280–286. https://doi.org/10.1128/iai.48.2.280-286.1985Contribution of cell surface protein antigen PAc of Streptococcus mutans to bacteremia / K. Nakano [et al.] // Microb. Infect. – 2006. – Vol. 8, N 1. – P. 114–121. https://doi.org/10.1016/j.micinf.2005.06.005Nakano K., Tsuji M., Nishimura K., Nomura R., Ooshima T. Contribution of cell surface protein antigen PAc of Streptococcus mutans to bacteremia. Microbes and Infection, 2006, vol. 8, no. 1, pp. 114–121. https://doi.org/10.1016/j.micinf.2005.06.005LT adjuvant modulates epitope specificity and improves the efficacy of murine antibodies elicited by sublingual vaccination with the N-terminal domain of Streptococcus mutans P1 / M. T. Batista [et al.] // Vaccine. – 2017. – Vol. 35, N 52. – P. 7273–7282. https://doi.org/10.1016/j.vaccine.2017.11.007Batista M. T., Ferreira E. L., Pereira G. S., Stafford P., Maeda D. L. N. F., Rodrigues J. F., Brady L. J., Johnston S. A., Ferreira L. C. S., Ferreira R. C. C. LT adjuvant modulates epitope specificity and improves the efficacy of murine antibodies elicited by sublingual vaccination with the N-terminal domain of Streptococcus mutans P1. Vaccine, 2017, vol. 35, no. 52, pp. 7273–7282. https://doi.org/10.1016/j.vaccine.2017.11.007UniProt: the Universal Protein knowledgebase / R. Apweiler [et al.] // Nucl. Acids Res. – 2004. – Vol. 32. – P. D115–D119. https://doi.org/10.1093/nar/gkh131Apweiler R., Bairoch A., Wu C. H., Barker W. C., Boeckmann B., Ferro S. [et al.]. UniProt: the universal protein knowledgebase. Nucleic Acids Research, 2004, vol. 32, pp. D115–D119. https://doi.org/10.1093/nar/gkh131Highly accurate protein structure prediction with AlphaFold / J. Jumper [et al.] // Nature. – 2021. – Vol. 596, N 7873. – P. 583–589. https://doi.org/10.1038/s41586-021-03819-2Jumper J., Evans R., Pritzel A., Green T., Figurnov M., Ronneberger O. [et al.]. Highly accurate protein structure prediction with AlphaFold. Nature, 2021, vol. 596, no. 7873, pp. 583–589. https://doi.org/10.1038/s41586-021-03819-2The PentUnFOLD algorithm as a tool to distinguish the dark and the light sides of the structural instability of proteins / V. V. Poboinev [et al.] // Amino Acids. – 2022. – Vol. 54, N 8. – P. 1155–1171. https://doi.org/10.1007/s00726-022-03153-5Poboinev V. V., Khrustalev V. V., Khrustaleva T. A., Kasko T. E., Popkov V. D. The PentUnFOLD algorithm as a tool to distinguish the dark and the light sides of the structural instability of proteins. Amino Acids, 2022, vol. 54, no. 8, pp. 1155–1171. https://doi.org/10.1007/s00726-022-03153-5Khrustalev, V. V. The PentaFOLD 3.0 algorithm for the selection of stable elements of secondary structure to be included in vaccine peptides / V. V. Khrustalev // Protein Pept. Lett. – 2021. – Vol. 28, N 5. – P. 573–588. https://doi.org/10.2174/0929866527666201110123851Khrustalev V. V. The PentaFOLD 3.0 algorithm for the selection of stable elements of secondary structure to be included in vaccine peptides. Protein and Peptide Letters, 2021, vol. 28, no. 5, pp. 573–588. https://doi.org/10.2174/0929866527666201110123851Smith, T. F. Identification of common molecular subsequences / T. F. Smith, M. S. Waterman // J. Mol. Biol. – 1981. – Vol. 147, N 1. – P. 195–197. https://doi.org/10.1016/0022-2836(81)90087-5Smith T. F., Waterman M. S. Identification of common molecular subsequences. Journal of Molecular Biology, 1981, vol. 147, no. 1, pp. 195–197. https://doi.org/10.1016/0022-2836(81)90087-5Eisenberg, D. VERIFY3D: assessment of protein models with three-dimensional profiles / D. Eisenberg, R. Lüthy, J. U. Bowie // Methods Enzymol. – 1997. – Vol. 277. – P. 396–404. https://doi.org/10.1016/s0076-6879(97)77022-8Eisenberg D., Lüthy R., Bowie J. U. VERIFY3D: assessment of protein models with three-dimensional profiles. Methods in Enzymology, 1997, vol. 277, pp. 396–404. https://doi.org/10.1016/s0076-6879(97)77022-8PROCHECK: a program to check the stereochemical quality of protein structures / R. A. Laskowski [et al.] // J. App. Cryst. – 1993. – Vol. 26. – P. 283–291. https://doi.org/10.1107/s0021889892009944Laskowski R. A., MacArthur M. W., Moss D. S., Thornton J. M. PROCHECK: a program to check the stereochemical quality of protein structures. Journal of Applied Crystallography, 1993, vol. 26, pp. 283–291. https://doi.org/10.1107/s0021889892009944An intramolecular lock facilitates folding and stabilizes the tertiary structure of Streptococcus mutans adhesin P1 / K. P. Heim [et al.] // Proc. Natl. Acad. Sci USA. – 2014. – Vol. 111, N 44. – P. 15746–15751. https://doi.org/10.1073/pnas.1413018111Heim K. P., Crowley P. J., Long J. R., Kailasan S., McKenna R., Brady L. J. An intramolecular lock facilitates folding and stabilizes the tertiary structure of Streptococcus mutans adhesin P1. Proceedings of the National Academy of Sciences of the United States of America, 2014, vol. 111, no. 44, pp. 15746–15751. https://doi.org/10.1073/pnas.1413018111Engineering protein stability with atomic precision in a monomeric miniprotein / E. G. Baker [et al.] // Nat. Chem. Biol. – 2017. – Vol. 13, N 7. – P. 764–770. https://doi.org/10.1038/nchembio.2380Baker E. G., Williams C., Hudson K. L., Bartlett G. J., Heal J. W., Porter Goff K. L., Sessions R. B., Crump M. P., Woolfson D. N. Engineering protein stability with atomic precision in a monomeric miniprotein. Nature Chemical Biology, 2017, vol. 13, no. 7, pp. 764–770. https://doi.org/10.1038/nchembio.2380The cytoplasmic tail of influenza A/H1N1 virus hemagglutinin is β-structural / V. V. Khrustalev [et al.] // J. Biomol. Struct. Dyn. – 2022. – Vol. 40, N 10. – P. 4642–4661. https://doi.org/10.1080/07391102.2020.1860827Khrustalev V. V., Kordyukova L. V., Arutyunyan A. M., Poboinev V. V., Khrustaleva T. A., Stojarov A. N., Baratova L. A., Sapon A. S., Lugin V. G. The cytoplasmic tail of influenza A/H1N1 virus hemagglutinin is β-structural. Journal of Biomolecular Structure and Dynamics, 2022, vol. 40, no. 10, pp. 4642–4661. https://doi.org/10.1080/07391102.2020.1860827Peptide models of the cytoplasmic tail of influenza A/H1N1 virus hemagglutinin expand understanding its pH-dependent modes of interaction with matrix protein M1 / V. V. Poboinev [et al.] // Protein J. – 2023. – Vol. 42, N 4. – P. 288–304. https://doi.org/10.1007/s10930-023-10101-zPoboinev V. V., Khrustalev V. V., Akunevich A. A., Shalygo N. V., Stojarov A. N., Khrustaleva T. A., Kordyukova L. V. Peptide models of the cytoplasmic tail of influenza A/H1N1 virus hemagglutinin expand understanding its pH-dependent modes of interaction with matrix protein M1. Protein Journal, 2023, vol. 42, no. 4, pp. 288–304. https://doi.org/10.1007/s10930-023-10101-z

The authors declare that there are no conflicts of interest present.