Molecular modelling studies to suggest novel scaffolds against SARS-CoV-2 target enzymes

Ahmet Fatih Şahin; Ş. Güniz Küçükgüzel; Atilla Akdemir

Molecular modelling studies to suggest novel scaffolds against SARS-CoV-2 target enzymes

Abstract

In this study, molecular modelling study of previously synthesized compounds against SARS-CoV-2 target enzyme was performed. A subset of 156 compounds from an in-house database has been subjected to molecular modelling studies against the SARS-CoV-2 ADP-ribose phosphatase (ADRP, NSP3), Papain-like protease (PLpro), and uridine specific endoribonuclease (NSP15) enzymes. We have identified one compound that is expected to inhibit the SARS-CoV-2 ADRP enzyme and one compound that is expected to inhibit the NSP15 enzyme.

Keywords

References

[1] Hu B, Guo H, Zhou P, Shi ZL. Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol. 2021; 19(3): 141- 154.
[2] Satarker S, Nampoothiri M. Structural Proteins in Severe Acute Respiratory Syndrome Coronavirus-2. Arch Med Res. 2020; 51(6): 482-491.
[3] Gordon DE, Jang GM, Bouhaddou M, et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020; 583(7816): 459-468.
[4] Prajapat M, Sarma P, Shekhar N, Avti P, Sinha S, Kaur H, Kumar S, Bhattacharyya A, Kumar H, Bansal S, Medhi B.. Drug targets for corona virus: A systematic review. Indian J Pharmacol. 2020; 52(1): 56-65.
[5] Raj R. Analysis of non-structural proteins, NSPs of SARS-CoV-2 as targets for computational drug designing. Biochem Biophys Rep. 2020; 25: 100847.
[6] Michalska K, Kim Y, Jedrzejczak R, Maltseva NI, Stols L, Endres M, Joachimiak A.Crystal structures of SARS-CoV-2 ADP-ribose phosphatase: from the apo form to ligand complexes. IUCrJ. 2020; 7(Pt 5): 814-824.
[7] Xu Y, Cong L, Chen C, Wei L, Zhao Q, Xu X, Ma Y, Bartlam M, Rao Z. Crystal structures of two coronavirus ADP- ribose-1''-monophosphatases and their complexes with ADP-Ribose: a systematic structural analysis of the viral ADRP domain. J Virol. 2009; 83(2): 1083-1092.
[8] Rajpoot S, Alagumuthu M, Baig MS. Dual targeting of 3CLpro and PLpro of SARS-CoV-2: A novel structure-based design approach to treat COVID-19. Curr Res Struct Biol. 2021; 3: 9-18.

[9] Pillon MC, Frazier MN, Dillard LB, Williams JG, Kocaman S, Krahn JM, Perera L, Hayne CK, Gordon J, Stewart ZD, Sobhany M, Deterding LJ, Hsu AL, Dandey VP, Borgnia MJ, Stanley RE. Cryo-EM structures of the SARS-CoV-2 endoribonuclease Nsp15 reveal insight into nuclease specificity and dynamics. Nat Commun. 2021; 12(1): 636.
[10] Hackbart M, Deng X, Baker SC. Coronavirus endoribonuclease targets viral polyuridine sequences to evade activating host sensors. Proc Natl Acad Sci USA. 2020; 117(14): 8094-8103.
[11] Aydın S, Kaushik-Basu N, Arora P, Basu A, Brian Nichols D, T Talele T, Akkurt M, Çelik İ, Büyükgüngör O, Küçükgüzel ŞG. Microwave assisted synthesis of some novel Flurbiprofen hydrazidehydrazones as anti-HCV NS5B and anticancer agents. Marmara Pharm J. 2013; 17(1): 26-34.
[12] Aydın S, Kaushik-Basu N, Ozbas-Turan S, Akbuga J, Mega-Tiber P, Orun O, Gurukumar KR, Basu A, Küçükgüzel ŞG. Synthesis of 1-aroyl-3,5-dimethyl-1H-pyrazoles as anti-HCV and anticancer agents. Lett Drug Des Discov. 2014; 11(2): 121-131.
[13] Küçükgüzel G, Kocatepe A, De Clercq E, Sahin F, Güllüce M. Synthesis and biological activity of 4-thiazolidinones, thiosemicarbazides derived from diflunisal hydrazide. Eur J Med Chem. 2006; 41(3): 353-359. Research Article
[14] Küçükgüzel SG, Küçükgüzel I, Tatar E, Rollas S, Sahin F, Güllüce M, De Clercq E, Kabasakal L. Synthesis of some novel heterocyclic compounds derived from diflunisal hydrazide as potential anti-infective and anti-inflammatory agents. Eur J Med Chem. 2007; 42(7): 893-901.
[15] Şenkardeş S, Kaushik-Basu N, Durmaz İ, Manvar D, Basu A, Atalay R, Küçükgüzel ŞG. Synthesis of novel diflunisal hydrazide-hydrazones as anti-hepatitis C virus agents and hepatocellular carcinoma inhibitors. Eur J Med Chem. 2016;108: 301-308.
[16] Şenkardeş S, Özakpınar ÖB, Özsavcı D, Şener A, Çevik Ö, Küçükgüzel ŞG. Synthesis of diflunisal thiazolidinones as anticancer agents. Anticancer Agents Med Chem. 2016;16(10): 1266-1274.
[17] Karakuş S, Küçükgüzel ŞG, Küçükgüzel I, De Clercq E, Pannecouque C, Andrei G, Snoeck R, Sahin F, Bayrak OF. Synthesis, antiviral and anticancer activity of some novel thioureas derived from N-(4-nitro-2-phenoxyphenyl)- methanesulfonamide. Eur J Med Chem. 2009;44(9):3591-3595.
[18] Küçükgüzel ŞG, Coşkun İ, Aydın S, Aktay G, Gürsoy Ş, Çevik Ö, Özakpınar ÖB, Özsavcı D, Şener A, Kaushik-Basu N, Basu A, Talele TT. Synthesis and characterization of celecoxib derivatives as possible anti-inflammatory, analgesic, antioxidant, anticancer and anti-HCV agents. Molecules. 2013;18(3):3595-3614.
[19] Coşkun GP, Djikic T, Hayal TB, Türkel N, Yelekçi K, Şahin F, Küçükgüzel ŞG. Synthesis, Molecular Docking and Anticancer Activity of Diflunisal Derivatives as Cyclooxygenase Enzyme Inhibitors. Molecules. 2018;23(8):1969.
[20] Coşkun GP, Djikic T, Kalaycı S, Yelekçi K, Şahin F, Küçükgüzel ŞG. Synthesis, Molecular Modelling and antibacterial activity against Helicobacter pylori of novel diflunisal derivatives as urease enzyme inhibitors. Lett Drug Des Discov. 2019;16(4): 392-400.

Details

Primary Language

English

Subjects

Pharmaceutical Chemistry

Journal Section

Research Article

Authors

Ahmet Fatih Şahin ^* This is me
Türkiye

Ş. Güniz Küçükgüzel
Türkiye

Atilla Akdemir
Türkiye

Publication Date

June 28, 2025

Submission Date

July 12, 2021

Acceptance Date

October 23, 2021

Published in Issue

Year 2021 Volume: 25 Number: 6

IZ

https://izlik.org/JA99PK25UN

Cite

RIS / Bibtex

APA

Şahin, A. F., Küçükgüzel, Ş. G., & Akdemir, A. (2025). Molecular modelling studies to suggest novel scaffolds against SARS-CoV-2 target enzymes. Journal of Research in Pharmacy, 25(6), 1010-1017. https://izlik.org/JA99PK25UN

AMA

1.Şahin AF, Küçükgüzel ŞG, Akdemir A. Molecular modelling studies to suggest novel scaffolds against SARS-CoV-2 target enzymes. J. Res. Pharm. 2025;25(6):1010-1017. https://izlik.org/JA99PK25UN

Chicago

Şahin, Ahmet Fatih, Ş. Güniz Küçükgüzel, and Atilla Akdemir. 2025. “Molecular Modelling Studies to Suggest Novel Scaffolds Against SARS-CoV-2 Target Enzymes”. Journal of Research in Pharmacy 25 (6): 1010-17. https://izlik.org/JA99PK25UN.

EndNote

Şahin AF, Küçükgüzel ŞG, Akdemir A (July 1, 2025) Molecular modelling studies to suggest novel scaffolds against SARS-CoV-2 target enzymes. Journal of Research in Pharmacy 25 6 1010–1017.

IEEE

[1]A. F. Şahin, Ş. G. Küçükgüzel, and A. Akdemir, “Molecular modelling studies to suggest novel scaffolds against SARS-CoV-2 target enzymes”, J. Res. Pharm., vol. 25, no. 6, pp. 1010–1017, July 2025, [Online]. Available: https://izlik.org/JA99PK25UN

ISNAD

Şahin, Ahmet Fatih - Küçükgüzel, Ş. Güniz - Akdemir, Atilla. “Molecular Modelling Studies to Suggest Novel Scaffolds Against SARS-CoV-2 Target Enzymes”. Journal of Research in Pharmacy 25/6 (July 1, 2025): 1010-1017. https://izlik.org/JA99PK25UN.

JAMA

1.Şahin AF, Küçükgüzel ŞG, Akdemir A. Molecular modelling studies to suggest novel scaffolds against SARS-CoV-2 target enzymes. J. Res. Pharm. 2025;25:1010–1017.

MLA

Şahin, Ahmet Fatih, et al. “Molecular Modelling Studies to Suggest Novel Scaffolds Against SARS-CoV-2 Target Enzymes”. Journal of Research in Pharmacy, vol. 25, no. 6, July 2025, pp. 1010-7, https://izlik.org/JA99PK25UN.

Vancouver

1.Ahmet Fatih Şahin, Ş. Güniz Küçükgüzel, Atilla Akdemir. Molecular modelling studies to suggest novel scaffolds against SARS-CoV-2 target enzymes. J. Res. Pharm. [Internet]. 2025 Jul. 1;25(6):1010-7. Available from: https://izlik.org/JA99PK25UN