Ukr.Biochem.J. 2021; Volume 93, Issue 5, Sep-Oct, pp. 43-51


Determination the binding ability of N-acetyl cysteine and its derivatives with SARS-COV-2 main protease using molecular docking and molecular dynamics studies

A. H. Shntaif*, N. A. Alrazzak, A. Bader, A. M. Almarzoqi

University of Babylon, College of Science for Women, Iraq;

Received: 25 May 2021; Accepted: 22 September 2021

N-acetyl cysteine (NAC) drug has been used as an antioxidant and  anti-inflammatory agent in clinical practice and more recently in the treatment of COVID-19 patients. Using docking analysis and molecular dynamics studies we compare the interaction between of N-acetyl cysteine and its derivatives with SARS-COV-2 main protease (Mpro) which is essential for processing the proteins translated from the viral RNA. The results obtained from this study showed that NAC benzyl ester (NACBn), NAC ethyl ester (NACEt) and NAC amide (NACA) could bind with SARS-COV-2 protease better than NAC drug.

Keywords: , , , , ,


  1. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-273. PubMed, PubMedCentral, CrossRef
  2. Gorbalenya AE, Baker SC, Baric RS, de Groot RJ, Drosten C, Gulyaeva AA, Haagmans BL, Lauber C, Leontovich AM, Neuman BW, Penzar D, Perlman S, Poon LLM, Samborskiy DV, Sidorov IA, Sola I, Ziebuhr J. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020;5(4):536-544. PubMed, PubMedCentral, CrossRef
  3. Hui DS, Azhar EI , Madani TA, Ntoumi F, Kock R, Dar O, Ippolito G, Mchugh TD, Memish ZA, Drosten C, Zumla A, Petersen E. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health – The latest 2019 novel coronavirus outbreak in Wuhan, China. Int J Infect Dis. 2020;91:264-266. PubMed, PubMedCentral, CrossRef
  4. Ren LL, Wang YM, Wu ZQ, Xiang ZC, Guo L, Xu T, Jiang YZ, Xiong Y, Li YJ, Li XW, Li H, Fan GH, Gu XY, Xiao Y, Gao H, Xu JY, Yang F, Wang XM, Wu C, Chen L, Liu YW, Liu B, Yang J, Wang XR, Dong J, Li L, Huang CL, Zhao JP, Hu Y, Cheng ZS, Liu LL, Qian ZH, Qin C, Jin Q, Cao B, Wang JW. Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study. Chin Med J (Engl). 2020;133(9):1015-1024.  PubMed, PubMedCentral, CrossRef
  5. Cui J, Li F, Shi ZL. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol. 2019;17(3):181-192. PubMed, PubMedCentral, CrossRef
  6. Chou CC, Shen CF, Chen SJ, Chen HM, Wang YC, Chang WS, Chang YT, Chen WY, Huang CY, Kuo CC, Li MC, Lin JF, Lin SP, Ting SW, Weng TC, Wu PS, Wu UI, Lin PC, Lee SSJ, Chen YS, Liu YC, Chuang YC, Yu CJ, Huang LM, Lin MC. Recommendations and guidelines for the treatment of pneumonia in Taiwan. J Microbiol Immunol Infect. 2019;52(1):172-199. PubMed, CrossRef
  7. Su IC, Lee KL, Liu HY, Chuang HC, Chen LY, Lee YJ. Severe community-acquired pneumonia due to Pseudomonas aeruginosa coinfection in an influenza A(H1N1)pdm09 patient. J Microbiol Immunol Infect. 2019;52(2):365-366. PubMed, CrossRef
  8. Hung HM, Yang SL, Chen CJ, Chiu CH, Kuo CY, Huang KYA, Lin TY, Hsieh YC, Gong YN, Tsao KC, Huang YC. Molecular epidemiology and clinical features of rhinovirus infections among hospitalized patients in a medical center in Taiwan. J Microbiol Immunol Infect. 2019;52(2):233-241. PubMed, CrossRef
  9. Lin GL, Lu CY, Chen JM, Lee PI, Ho SY, Weng KC, Huang LM, Chang LY. Molecular epidemiology and clinical features of adenovirus infection in Taiwanese children, 2014. J Microbiol Immunol Infect. 2019;52(2):215-224. PubMed, CrossRef
  10. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu N, Bi Y, Ma X, Zhan F, Wang L, Hu T, Zhou H, Hu Z, Zhou W, Zhao L, Chen J, Meng Y, Wang J, Lin Y, Yuan J, Xie Z, Ma J, Liu WJ, Wang D, Xu W, Holmes EC, Gao GF, Wu G, Chen W, Shi W, Tan W. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395(10224):565-574. PubMed, PubMedCentral, CrossRef
  11. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G , Gao GF, Tan W. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020;382(8):727-733. PubMed, PubMedCentral, CrossRef
  12. Simmonds P, Adams MJ, Benkő M, Breitbart M, Brister JR, Carstens EB, Davison AJ, Delwart E, Gorbalenya AE, Harrach B, Hull R, King AMQ, Koonin EV, Krupovic M, Kuhn JH, Lefkowitz EJ, Nibert ML, Orton R, Roossinck MJ, Sabanadzovic S, Sullivan MB, Suttle CA, Tesh RB, van der Vlugt RA, Varsani A, Zerbini FM. Consensus statement: Virus taxonomy in the age of metagenomics. Nat Rev Microbiol. 2017;15(3):161-168. PubMed, CrossRef
  13. Chen L, Liu W, Zhang Q, Xu K, Ye G, Wu W, Sun Z, Liu F, Wu K, Zhong B, Mei Y, Zhang W, Chen Y, Li Y, Shi M, Lan K, Liu Y. RNA based mNGS approach identifies a novel human coronavirus from two individual pneumonia cases in 2019 Wuhan outbreak. Emerg Microbes Infect. 2020;9(1):313-319. PubMed, PubMedCentral, CrossRef
  14. Jiang S, Du L, Shi Z. An emerging coronavirus causing pneumonia outbreak in Wuhan, China: calling for developing therapeutic and prophylactic strategies. Emerg Microbes Infect. 2020;9(1):275-277. PubMed, PubMedCentral, CrossRef
  15. Li X, Song Y, Wong G, Cui J. Bat origin of a new human coronavirus: there and back again. Sci China Life Sci. 2020;63(3):461-462. PubMed, PubMedCentral, CrossRef
  16. Zhang L, Lin D, Sun X, Curth U, Drosten C, Sauerhering L, Becker S, Rox K, Hilgenfeld R. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science. 2020;368(6489):409-412. PubMed, PubMedCentral, CrossRef
  17. Jin Z, Du X, Xu Y, Deng Y, Liu M, Zhao Y, Zhang B, Li X, Zhang L, Peng C, Duan Y, Yu J, Wang L, Yang K, Liu F, Jiang R, Yang X, You T, Liu X, Yang X, Bai F, Liu H, Liu X, Guddat LW, Xu W, Xiao G, Qin C, Shi Z, Jiang H, Rao Z, Yang H. Structure of M pro from SARS-CoV-2 and discovery of its inhibitors. Nature. 2020;582(7811):289-293. PubMed, , CrossRef
  18. Vranová E, Inzé D, Van Breusegem F. Signal transduction during oxidative stress. J Exp Bot. 2002;53(372):1227-1236. PubMed, CrossRef
  19. Turpaev KT. Reactive oxygen species and regulation of gene expression. Biochemistry (Mosc). 2002;67(3):281-292. PubMed, CrossRef
  20. Sanguinetti CM. N-acetylcysteine in COPD: why, how, and when? Multidiscip Respir Med. 2016;11:8. PubMed, PubMedCentral, CrossRef
  21. Gunnell D, Murray V, Hawton K. Use of paracetamol (acetaminophen) for suicide and nonfatal poisoning: worldwide patterns of use and misuse. Suicide Life Threat Behav. 2000;30(4):313-326. PubMed
  22. Cairney DG, Beckwith HKS, Al-Hourani K, Eddleston M, Bateman DN, Dear JW. Plasma paracetamol concentration at hospital presentation has a dose-dependent relationship with liver injury despite prompt treatment with intravenous acetylcysteine. Clin Toxicol (Phila). 2016;54(5):405-410. PubMed, CrossRef
  23. Samuni Y, Goldstei S, Dean OM, Berk M. The chemistry and biological activities of N-acetylcysteine. Biochim Biophys Acta. 2013;1830(8):4117-4129. PubMed, CrossRef
  24. Omara FO, Blakley BR, Bernier J, Fournier M. Immunomodulatory and protective effects of N-acetylcysteine in mitogen-activated murine splenocytes in vitro. Toxicology. 1997;116(1-3):219-226. PubMed, CrossRef
  25. Shi Z, Puyo CA. N-Acetylcysteine to Combat COVID-19: An Evidence Review. Ther Clin Risk Manag. 2020;16:1047-1055. PubMed, PubMedCentral, CrossRef
  26. Guthappa R. Molecular Docking Studies of N-Acetyl Cysteine, Zinc Acetyl Cysteine and Niclosamide on SARS Cov 2 Protease and Its Comparison with Hydroxychloroquine. ChemRxiv. Cambridge: Cambridge Open Engage; 2020. Preprint. CrossRef
  27. Thimmasandra Narayan R. Binding Ability Studies of Arginine, Citrulline, N-Acetyl Citrulline and Thiocitrulline with SARS Cov-2 Main Protease Using Molecular Docking Studies. ChemRxiv. Cambridge: Cambridge Open Engage; 2020. Preprint. CrossRef
  28. Badavath VN, Kumar A, Samanta PK, Maji S, Das A, Blum G, Jha A, Sen A. Determination of potential inhibitors based on isatin derivatives against SARS-CoV-2 main protease (m pro): a molecular docking, molecular dynamics and structure-activity relationship studies. J Biomol Struct Dyn. 2020;1-19. PubMed, PubMedCentral, CrossRef
  29. Xue X, H Yu, Yang H, Xue F, Wu Z, Shen W, Li J, Zhou Z, Ding Y, Zhao Q, Zhang XC, Liao M, Bartlam M, Rao Z. Structures of two coronavirus main proteases: implications for substrate binding and antiviral drug design. J Virol. 2008;82(5):2515-2527. PubMed, PubMedCentral, CrossRef

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