Antiviral peptidlerin SARS COV-2 ana proteaz yapısına bağlanma etkinliklerinin protein-yanaştırma yöntemi ile incelenmesi: In silico bir çalışma

Year 2022, , 121 - 127, 30.12.2022

İlter Demirhan , Erkan Öner , Ergul Belge Kurutas

https://doi.org/10.51753/flsrt.1092767

Abstract

Virüsler günümüzde hastalıklarının önemli etkenleri arasında yer almaktadır. Viral hastalıklar için tasarlanan tedavilerin yetersizliği yeni tedavi yöntemlerinin tasarlanması ihtiyacını doğurmaktadır. 2019 yılında ortaya çıkan COVID-19 (SARS COV-2) de yeni antiviral ajanların ihtiyacı olduğu görülmüştür. Yapılan çalışmalar sonucu sunulan raporlarda viral direncin artığı görülmektedir. Bu çalışmanın amacı, antiviral/antimikrobiyal etkinliğe sahip peptidlerin SARS COV-2 ana proteaz yapısında protein-peptid yanaştırma yöntemiyle araştırılmasıdır. Antiviral aktiviteye sahip antimikrobiyal peptidlerin sayısı hala düşük olsada, hali hazırda farmasötik olarak temin edilebilen antiviral ilaçlar olma yolunda muazzam bir potansiyel göstermektedir. Antiviral etkinliğe sahip alloferon 1, e ctry2801, temporin 1ta, dermaseptin s4, clavanin b, magainin b2 ve magainin b1 peptidlerinin SARS COV-2 ana proteaz (PDB ID:6LU7) yapısında protein çalışması CABSDOCK ile yapılmıştır. Magainin b2 ve peptid ctyr2801 peptidleri bağlanmalarının yüksek düzeyde olduğu, alloferon 1 ve magainin b1 in orta düzeyde bağlanma afinitesinin olduğu, termorin 1ta, dermaseptin s4 ve clavanin b’nin düzey düzeyde bağlanma afinitesine sahip olduğu gözlemlenmiştir. Sonuçlarımıza göre; peptid ctyr2801 ve magainin b2’nin, SARS COV-2 ana proteaz yapısında in vivo çalışmalara ve diğer çalışmalara öncülük edeceği düşünülmektedir.

Keywords

Antiviral peptid, CABSDOCK, protein peptid yanaştırma, SARS COV-2 Mpro

Investigation of antiviral peptides in SARS COV-2 major protease structure by protein-e docking method: An in silico study

Abstract

Viruses are among the important factors of diseases today. The inadequacy of the treatments designed for viral diseases necessitates the design of new treatment methods. It has been seen that there is a need for new antiviral agents in COVID-19. In the reports presented as a result of the studies, it was seen that the viral resistance has increased. The aim of this study is to investigate peptides with antiviral/antimicrobial activity in the main protease (Mpro) structure of SARS COV-2 by protein-peptide docking method. Although the number of antimicrobial peptides with antiviral activity is still low, they still show enormous potential as pharmaceutically available antiviral drugs. Protein analysis of alloferon 1, ctry2801, temporin 1ta, dermaceptin-s4, clavanin b, magainin b2 and magainin b1 peptides with antiviral activity in the SARS COV-2 Mpro (PDB ID: 6LU7) structure was performed
with CABSDOCK. It has been observed that the binding affinity of magainin b2 and peptide ctyr2801 is high, alloferon 1 and magainin b1 have a moderate binding affinity, and thermorin-1ta, dermaseptin s4 and clavanin b have a high level of binding affinity. According to our results; Peptide ctyr2801 and magainin b2 are thought to lead to in vivo studies and other studies on the SARS COV-2 Mpro structure.

Keywords

Antiviral peptide, CABSDOCK, protein peptide docking, SARS COV-2 Mpro

References

• Altmann, S. E., Brandt, C. R., Jahrling, P. B., & Blaney, J. E. (2012). Antiviral activity of the EB peptide against zoonotic poxviruses. Virology Journal, 9(1), 1-6.
• Araf, Y., Akter, F., Tang, Y. D., Fatemi, R., Parvez, M. S. A., Zheng, C., & Hossain, M. G. (2022). Omicron variant of SARS‐COV‐2: genomics, transmissibility, and responses to current COVID‐19 vaccines. Journal of Medical Virology, 94(5), 1825-1832.
• Badani, H., Garry, R. F., & Wimley, W. C. (2014). Peptide entry inhibitors of enveloped viruses: the importance of interfacial hydrophobicity. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1838(9), 2180-2197.
• Barlow, P. G., Findlay, E. G., Currie, S. M., & Davidson, D. J. (2014). Antiviral potential of cathelicidins. Future Microbiology, 9(1), 55-73.
• Cantatore, A., Randall, S. D., Traum, D., & Adams, S. D. (2013). Effect of black tea extract on herpes simplex virus-1 infection of cultured cells. BMC Complementary and Alternative Medicine, 13(1), 1-10.
• Chen, L., Liu, Y., Wang, S., Sun, J., Wang, P., Xin, Q., ... & Wang, W. (2017). Antiviral activity of peptide inhibitors derived from the protein E stem against Japanese encephalitis and Zika viruses. Antiviral Research, 141, 140-149.
• Deming, P., & McNicholl, I. R. (2011). Coinfection with Human Immunodeficiency Virus and Hepatitis C Virus: Challenges and Therapeutic Advances: Insights from the Society of Infectious Diseases Pharmacists. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 31(4), 357-368.
• De Souza, W. V., Albuquerque, M. D. F. P. M. D., Vazquez, E., Bezerra, L. C. A., Mendes, A. D. C. G., Lyra, T. M., ... & Martelli, C. M. T. (2018). Microcephaly epidemic related to the Zika virus and living conditions in Recife, Northeast Brazil. BMC Public Health, 18(1), 1-7.
• Egal, M., Conrad, M., MacDonald, D. L., Maloy, W. L., Motley, M., & Genco, C. A. (1999). Antiviral effects of synthetic membrane-active peptides on herpes simplex virus, type 1. International Journal of Antimicrobial Agents, 13(1), 57-60.
• El-Bitar, A. M., Sarhan, M. M., Aoki, C., Takahara, Y., Komoto, M., Deng, L., ... & Hotta, H. (2015). Virocidal activity of Egyptian scorpion venoms against hepatitis C virus. Virology Journal, 12(1), 1-9.
• El Raziky, M., Fathalah, W. F., El-Akel, W. A., Salama, A., Esmat, G., Mabrouk, M., ... & Khatab, H. M. (2013). The effect of peginterferon alpha-2a vs. peginterferon alpha-2b in treatment of naive chronic HCV genotype-4 patients: a single centre Egyptian study. Hepatitis Monthly, 13(5).
• Elshabrawy, H. A., Fan, J., Haddad, C. S., Ratia, K., Broder, C. C., Caffrey, M., & Prabhakar, B. S. (2014). Identification of a broad-spectrum antiviral small molecule against severe acute respiratory syndrome coronavirus and Ebola, Hendra, and Nipah viruses by using a novel high-throughput screening assay. Journal of Virology, 88(8), 4353-4365.
• Genc, B. N. (2020). Critical management of COVID-19 pandemic in Turkey. Frontiers in Life Sciences and Related Technologies, 1(2), 69-73.
• Gupta, R.K. (2021). Will SARS COV-2 variants of concern affect the promise of vaccines? Nature Reviews Immunology, 21, 340-341.
• Hakim, A., Nguyen, J. B., Basu, K., Zhu, D. F., Thakral, D., Davies, P. L., ... & Meng, W. (2013). Crystal structure of an insect antifreeze protein and its implications for ice binding. Journal of Biological Chemistry, 288(17), 12295-12304.
• Hilgenfeld, R. (2014). From SARS to MERS: crystallographic studies on coronaviral proteases enable antiviral drug design. The FEBS Journal, 281(18), 4085-4096.
• Hengphasatporn, K., Garon, A., Wolschann, P., Langer, T., Yasuteru, S., Huynh, T. N., ... & Rungrotmongkol, T. (2020). Multiple virtual screening strategies for the discovery of novel compounds active against dengue virus: A hit identification study. Scientia Pharmaceutica, 88(1), 2-19.
• Hrobowski, Y. M., Garry, R. F., & Michael, S. F. (2005). Peptide inhibitors of dengue virus and West Nile virus infectivity. Virology Journal, 2(1), 1-10.
• Hui, D. S., Lee, N., & Chan, P. K. (2017). A clinical approach to the threat of emerging influenza viruses in the A sia‐P acific region. Respirology, 22(7), 1300-1312.
• Ishag, H. Z., Li, C., Huang, L., Sun, M. X., Ni, B., Guo, C. X., & Mao, X. (2013). Inhibition of Japanese encephalitis virus infection in vitro and in vivo by pokeweed antiviral protein. Virus Research, 171(1), 89-96.
• Jamroz, M., Kolinski, A., & Kmiecik, S. (2014). CABS-flex predictions of protein flexibility compared with NMR ensembles. Bioinformatics, 30(15), 2150-2154.
• Jesus, T., Rogelio, L., Abraham, C., Uriel, L., García, J., Alfonso, M. T., & Lilia, B. B. (2012). Prediction of antiviral peptides derived from viral fusion proteins potentially active against herpes simplex and influenza A viruses. Bioinformation, 8(18), 870.
• Jukic, M., Škrlj, B., Tomšič, G., Pleško, S., Podlipnik, Č., & Bren, U. (2021). Prioritisation of compounds for 3CLpro inhibitor development on SARS-COV-2 variants. Molecules, 26(10), 300-303.
• Kurcinski, M., & Kolinski, A. (2007). Hierarchical modeling of protein interactions. Journal of Molecular Modeling, 13(6), 691-698.
• Kiser, J. J., & Flexner, C. (2013). Direct-acting antiviral agents for hepatitis C virus infection. Annual Review of Pharmacology and Toxicology, 53, 427-449.
• Le Page, A. K., Jager, M. M., Iwasenko, J. M., Scott, G. M., Alain, S., & Rawlinson, W. D. (2013). Clinical aspects of cytomegalovirus antiviral resistance in solid organ transplant recipients. Clinical Infectious Diseases, 56(7), 1018-1029.
• Li, M., Lou, F., & Fan, H. (2021). SARS-COV-2 Variants of Concern Delta: a great challenge to prevention and control of COVID-19. Signal Transduction and Targeted Therapy, 6(1), 1-3.
• Lin, F. C., & Young, H. A. (2014). Interferons: success in anti-viral immunotherapy. Cytokine & Growth Factor Reviews, 25(4), 369-376.
• Lok, S. M., Costin, J. M., Hrobowski, Y. M., Hoffmann, A. R., Rowe, D. K., Kukkaro, P., ... & Michael, S. F. (2012). Release of dengue virus genome induced by a peptide inhibitor. PLoS One, 7(11), e50995.
• Lou, Z., Sun, Y., & Rao, Z. (2014). Current progress in antiviral strategies. Trends in Pharmacological Sciences, 35(2), 86-102.
• Lowe, R., Barcellos, C., Brasil, P., Cruz, O. G., Honório, N. A., Kuper, H., & Carvalho, M. S. (2018). The Zika virus epidemic in Brazil: from discovery to future implications. International Journal of Environmental Research and Public Health, 15(1), 96.
• Maccari, G., Di Luca, M., Nifosí, R., Cardarelli, F., Signore, G., Boccardi, C., & Bifone, A. (2013). Antimicrobial peptides design by evolutionary multiobjective optimization. PLoS Computational Biology, 9(9), e1003212.
• Mahmoud, A. (2016). New vaccines: Challenges of discovery. Microbial Biotechnology, 9(5), 549-552.
• Marston, B. J., Dokubo, E. K., van Steelandt, A., Martel, L., Williams, D., Hersey, S., ... & Redd, J. T. (2017). Ebola response impact on public health programs, West Africa, 2014–2017. Emerging Infectious Diseases, 23(Suppl 1), S25.
• Mohan, K. V., Rao, S. S., & Atreya, C. D. (2010). Antiviral activity of selected antimicrobial peptides against vaccinia virus. Antiviral Research, 86(3), 306-311.
• Mooney, C., Haslam, N.J., Pollastri, G., & Shields, D.C. (2012). Towards the improved discovery and design of functional es: common features of diverse classes permit generalized prediction of bioactivity. PLoS One, 7, 1-12.
• Mulder, K. C., Lima, L. A., Miranda, V. J., Dias, S. C., & Franco, O. L. (2013). Current scenario of peptide-based drugs: the key roles of cationic antitumor and antiviral peptides. Frontiers in Microbiology, 4, 321-344.
• Nielsen, M., Lundegaard, C., Blicher, T., Lamberth, K., Harndahl, M., Justesen, S., ... & Buus, S. (2007). NetMHCpan, a method for quantitative predictions of peptide binding to any HLA-A and-B locus protein of known sequence. PloS One, 2(8), e796.
• Okazaki, K., & Kida, H. (2004). A synthetic peptide from a heptad repeat region of herpesvirus glycoprotein B inhibits virus replication. Journal of General Virology, 85(8), 2131-2137.
• Qureshi, A., Thakur, N., Tandon, H., & Kumar, M. (2014). AVPdb: a database of experimentally validated antiviral peptides targeting medically important viruses. Nucleic Acids Research, 42(D1), D1147-D1153.
• Rothan, H. A., Bahrani, H., Rahman, N. A., & Yusof, R. (2014). Identification of natural antimicrobial agents to treat dengue infection: In vitro analysis of latarcin peptide activity against dengue virus. BMC Microbiology, 14(1), 1-10.
• Sharma, A., Singla, D., Rashid, M., & Raghava, G. P. S. (2014). Designing of peptides with desired half-life in intestine-like environment. BMC Bioinformatics, 15(1), 1-8.
• Shoichet, B. K. (2006). Interpreting steep dose-response curves in early inhibitor discovery. Journal of Medicinal Chemistry, 49(25), 7274-7277.
• Steczkiewicz, K., Zimmermann, M. T., Kurcinski, M., Lewis, B. A., Dobbs, D., Kloczkowski, A., ... & Ginalski, K. (2011). Human telomerase model shows the role of the TEN domain in advancing the double helix for the next polymerization step. Proceedings of the National Academy of Sciences, 108(23), 9443-9448.
• Thompson, C., & Whitley, R. (2011). Neonatal herpes simplex virus infections: where are we now?. Hot Topics in Infection and Immunity in Children VII, 221-230.
• Wang, W., Owen, S. M., Rudolph, D. L., Cole, A. M., Hong, T., Waring, A. J., ... & Lehrer, R. I. (2004). Activity of α-and θ-defensins against primary isolates of HIV-1. The Journal of Immunology, 173(1), 515-520.
• Yu, Y., Deng, Y. Q., Zou, P., Wang, Q., Dai, Y., Yu, F., ... & Lu, L. (2017). A peptide-based viral inactivator inhibits Zika virus infection in pregnant mice and fetuses. Nature Communications, 8(1), 1-12.
• Zambrano, R., Jamroz, M., Szczasiuk, A., Pujols, J., Kmiecik, S., & Ventura, S. (2015). AGGRESCAN3D (A3D): server for prediction of aggregation properties of protein structures. Nucleic Acids Research, 43(W1), W306-W313.
• Zapata, W., Aguilar-Jiménez, W., Feng, Z., Weinberg, A., Russo, A., Potenza, N., ... & Rugeles, M. T. (2016). Identification of innate immune antiretroviral factors during in vivo and in vitro exposure to HIV-1. Microbes and Infection, 18(3), 211-219.
• Zhang, C. H., Stone, E. A., Deshmukh, M., Ippolito, J. A., Ghahremanpour, M. M., Tirado-Rives, J., ... & Jorgensen, W. L. (2021). Potent noncovalent inhibitors of the main protease of SARS-COV-2 from molecular sculpting of the drug perampanel guided by free energy perturbation calculations. ACS central science, 7(3), 467-475.
• Zhang, L., Lin, D., Kusov, Y., Nian, Y., Ma, Q., Wang, J., ... & Hilgenfeld, R. (2020). α-Ketoamides as broad-spectrum inhibitors of coronavirus and enterovirus replication: structure-based design, synthesis, and activity assessment. Journal of Medicinal Chemistry, 63(9), 4562-4578.
• Zhao, Z., Hong, W., Zeng, Z., Wu, Y., Hu, K., Tian, X., ... & Cao, Z. (2012). Mucroporin-M1 inhibits hepatitis B virus replication by activating the mitogen-activated protein kinase (MAPK) pathway and down-regulating HNF4α in vitro and in vivo. Journal of Biological Chemistry, 287(36), 30181-30190.