Development in antiviral drugs and the assessment

Abstract

The aim of antiviral therapy is to minimize the viral disease symptoms, infectiousness and shorten the treatment process. Antivirals act differently on viral replication cycle steps. However, nowadays, antiviral therapy is not available for all viral infections. Most antiviral drugs used in the treatment are effective in treating infections caused by HIV, herpes viruses, hepatitis B and C viruses, and influenza A and B viruses. Owing to viruses are mandatory, intracellular parasites, it is not very easy to find targets that prevent viral replication without damaging the host cell, as opposed to other antimicrobial drugs. Therefore, advances in treatment with antiviral drugs have been more lingering compared to antibacterial and antifungal drugs. This situation still continues today. In this study, antiviral drugs used during the treatment, differences and properties of these drugs was tried to be revealed by literature and the latest update on developments related to antiviral drugs was reviewed.

Keywords

• Virus,viral replication,viral infection,antiviral drug

Antiviral ilaçlardaki gelişmeler ve değerlendirilmesi

Abstract

Antiviral tedavinin amacı, viral hastalık semptomları ile bulaşıcılığı en alt düzeye indirmek ve tedavi sürecini kısaltmaktır. Antiviraller viral replikasyon basamaklarına farklı şekillerde etki ederler. Ancak günümüzde, antiviral tedavi tüm viral enfeksiyonlar için bulunmamaktadır. Tedavide kullanılan antiviral ilaçların çoğu, HIV, herpes virüsleri, hepatit B ve C virüsleri ve influenza A ve B virüslerinin neden olduğu enfeksiyonların tedavisinde etkindir. Virüslerin zorunlu, hücre içi parazitler olması nedeniyle, konak hücreye zarar vermeden viral replikasyonu önleyen hedefler bulmak diğer antimikrobiyal ilaçların aksine çok kolay değildir. Bu nedenle antiviral tedavideki gelişmeler gerek antibakteriyel gerekse antifungallere göre daha yavaş ilerleyen bir süreç olmuştur. Bu süreç günümüzde hala devam etmektedir. Bu çalışmada, viral tedavide kullanılan antiviral ilaçlar, bu ilaçların farklılıkları ve ilaçların özellikleri literatür verilerine dayanılarak ortaya konulmuş, antiviral ilaçlarla ilgili gelişmelere ait güncel bilgiler derlenmiştir.

Keywords

• Virüs,viral replikasyon,viral enfeksiyon,antiviral ilaç

References

1. 1. Antonelli G, Pistello M. Virology: a scientific discipline facing new challenges. Clin Microbiol Infect 2019;25(2):133-135.
2. 2. Graham L. Patrick, An Introduction to Medicinal Chemistery. 5th Edition; In: Patrick L. P., editors. Antiviral Agents. New York: OXFORD University Press; 2012. pp:468-513.
3. 3. Wohl S, Schaffner SF, Sabeti PC. Genomic Analysis of Viral Outbreaks. Annu Rev Virol 2016;3(1):173-195.
4. 4. Kates JR, McAuslan BR. Poxvirus DNA-dependent RNA polymerase. Proceedings of the National Academy of Sciences 1967;58:134–141.
5. 5. Oxford JS, Logan IS, Potter CW. In vivo selection of an influenza A2 strain resistant to amantadine. Nature 1970;226:82–83.
6. 6. Prusoff WH. Discussion of the possible mechanisms of action of 5-iodo-2′-deoxyuridine (IDU, IUDR) and chymotrypsin in the treatment of herpes simplex keratitis. Transactions - American Academy of Ophthalmology & Otolaryngology 1963;67:707–709.
7. 7. Hermann EC, Hermann JA. A working hypothesis – virus resistance development as an indicator of specific antiviral activity. Annals of the New York Academy of Sciences 1979;284:632–637.
8. 8. Littler E, Oberg B. Achievements and challenges in antiviral drug discovery. Antivir Chem Chemother 2005;16(3):155-68.

9. 9. Schaeffer HJ, et al. 9-(2-hydroxyethoxymethyl) guanine activity against viruses of the herpes group. Nature 1978; 272:583–585.
10. 10. Field HJ, De Clercq. E Antiviral drugs – a short history of their discovery and development. Microbiology Today 2004;31:58–61.
11. 11. De Chassey B, et al. New horizons for antiviral drug discovery from virus-host protein interaction networks. Curr Opin Virol. 2012;2(5):606-13.
12. 12. De Clercq E. Molecular targets for antiviral agents. J Pharmacol Exp Ther. 2001; 297(1):1-10.
13. 13. Ustaçelebi Ş. Virüslerin morfolojisi ve genel özellikleri. In: Ustaçelebi, Ş editors. Temel ve Klinik mikrobiyoloji. Ankara: Güneş kitapevi;1999. pp:746.
14. 14. Berdis AJ. DNA Polymerases as Therapeutic Targets. Biochemistry 2008;47(32): 8253–8260.
15. 15. Said ZN, Abdelwahab KS. Antiviral Replication Agents. In: Rosas-Acosta, G. editors. Chapter 6. Antiviral Replication Agents. London: Intech;2013:127144.
16. 16. Zoulim F, Lebosse F, Levrero M. Current treatments for chronic hepatitis B virüs infection. Current opinion in Virology 2016;18:109-16.
17. 17. McKnight KL, Heinz BA. RNA as a target for developing antivirals. Antivir Chem Chemother 2003;14(2):61-73.
18. 18. Beale JM. Wilson and Gisvold’s textbook of Organic Medicinal and Pharmaceutical Chemistry. In: Beale JM, Block JH editors. Antiviral Agents . Philadelphia: Lippincott Williams & Wilkins, a Wolters Kluwer; 2011:330-354.
19. 19. Patick AK, Potts KE. Protease Inhibitors as Antiviral Agents. Clin Microbiol Rev 1998;11(4): 614-627.
20. 20. Lv Z, Chu Y, Wang Y. HIV protease inhibitors: a review of molecular selectivity and toxicity. HIV AIDS 2015;8(7):95-104.
21. 21. Zając M, et al. Hepatitis C-New drugs and treatment prospects. Eur J Med Chem 2019;165:225-249.
22. 22. Sierra-Aragón S, Walter H. Targets for inhibition of HIV replication: entry, enzyme action, release and maturation. Intervirology 2012;55(2):84-97.
23. 23. Toniolo Neto J. Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children. Sao Paulo Med J 2014;132(4):256-257.
24. 24. Duwe S. Influenza viruses - antiviral therapy and resistance. GMS Infect Dis 2017;25:5
25. 25. Rollinger JM, Schmidtke M. The human rhinovirus: human-pathological impact, mechanisms of antirhinoviral agents, and strategies for their discovery. Med Res Rev 2011;31(1):42-92.
26. 26. Feld JJ, Hoffnagle JH. Mechanism of action of interferon anf ribavirin in treatment of hepatitis C. Nature 2005;436(7053): 967-972.
27. 27. Yenen OŞ. Hepatit C virüs. İn: Wıllke Topçu A, Söyletir G, Doğanay M. editors. İnfeksiyon hastalıkları ve mikrobiyolojisi. İstanbul: Nobel Tıp Kitapevi; 2002. pp:1377.
28. 28. Schott G, et al. Differential effects of viral silencing suppressors on siRNA and miRNA loading support the existence of two distinct cellular pools of ARGONAUTE1. EMBO J 2012; 31: 2553-2565.
29. 29. Mollaie HR, et al. RNAi and miRNA in viral infections and cancers. Asian Pac J Cancer Prev 2013;14(12):7045-7056.
30. 30. Janssen HL, et al. Treatment of HCV infection by targeting microRNA. N Engl J Med 2013;368(18):1685-1694.
31. 31. Rogers GL, Cannon PM. Gene Therapy Approaches to Human Immunodeficiency Virus and Other Infectious Diseases. Hematol Oncol Clin North Am 2017;31(5):883-895.
32. 32. Soppe JA, Lebbink RJ. Antiviral Goes Viral: Harnessing CRISPR/Cas9 to Combat Viruses in Humans. Trends Microbiol. 2017;25(10):833-850.
33. 33.Deans C, Maggert KA. What do you mean, “epigenetic”? Genetics 2015;199: 887–896.
34. 34. Nehme Z, Pasquereau S, Herbein G. Control of viral infections by epigenetic-targeted therapy. Clin Epigenetics 2019;11(1):55.