Ukr.Biochem.J. 2023; Volume 95, Issue 1, Jan-Feb, pp. 90-102

doi: https://doi.org/10.15407/ubj95.01.090

Cathepsin inhibitors as potent inhibitors against SARS-CoV-2 main protease. In silico molecular screening and toxicity prediction

17.04.2023   Uncategorized   No comments

O. Sekiou1*, W. Kherfane2, M. Boumendjel3,
H. Cheniti4, A. Benselhoub1*, S. Bellucci5

1Environmental Research Center, Annaba, Algeria;
2Laboratory of Geodynamics and Natural Resources, Department of Hydraulics,
Badji Mokhtar Annaba University, Annaba, Algeria;
3Laboratory of Biochemistry and Environmental Toxicology,
Badji Mokhtar Annaba University, Algeria;
4National High School of Technology and Engineering (ESTI), Annaba, Algeria;
5INFN Frascati National Laboratories, Rome, Italy;
*e-mail: aissabenselhoub@cre.dz; sekiouomar@yahoo.fr

Received: 05 March 2023; Revised: 28 March 2023;
Accepted: 13 April 2023; Available on-line: 27 April 2023

Since the emergence of the newly identified Coronavirus SARS-CoV-2, no targeted therapeutic agents for COVID-19 treatment are available, and effective treatment options remain very limited. Successful crystallization of the SARS-CoV-2 main protease (Mpro, PDB-ID 6LU7) made possible the research on finding its potential inhibitors for the prevention of virus replication. To conduct molecular docking, we selected ten representatives of the Cathepsin inhibitors family as possible ligands with a high potential of binding the active site of SARS-CoV-2 main protease as a potential target. The results of molecular docking studies revealed that Ligand1 and Ligand2, with vina scores -8.8 and -8.7 kcal/mol for Mpro, respectively, were the most effective in binding. In silico prediction of physicochemical and toxicological behavior of assessed ligands approved the possibility of their use in clinical essays against SARS-COVID-19.

Keywords: , , , , , ,

References:

  1. Li H, Liu SM , Yu XH, Tang SL, Tang CK. Coronavirus disease 2019 (COVID-19): current status and future perspectives. Int J Antimicrob Agents. 2020;55(5):105951. PubMed, PubMedCentral, CrossRef
  2. Kim JM, Chung YS, Jo HJ, Lee NJ, Kim MS, Woo SH, Park S, Kim JW, Kim HM, Han MG. Identification of Coronavirus Isolated from a Patient in Korea with COVID-19. Osong Public Health Res Perspect. 2020;11(1):3-7. PubMed, PubMedCentral, CrossRef
  3. Elgin TG, Fricke EM, Hernandez Reyes ME, Tsimis ME, Leslein NS, Thomas BA, Sato TS, McNamara PJ. The changing landscape of SARS-CoV-2: Implications for the maternal-infant dyad. J Neonatal Perinatal Med. 2020;13(3):293-305. PubMed, PubMedCentral, CrossRef
  4. 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
  5. Cascella M, Rajnik M, Aleem A, Dulebohn SC, Di Napoli R. Features, Evaluation, and Treatment of Coronavirus (COVID-19). StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022. PubMed
  6. Zhai P, Ding Y, Wu X, Long J, Zhong Y, Li Y. The epidemiology, diagnosis and treatment of COVID-19. Int J Antimicrob Agents. 2020;55(5):105955. PubMed, PubMedCentral, CrossRef
  7. Durante-Mangoni E, Andini R, Bertolino L, Mele F, Florio LL, Murino P, Corcione A, Zampino R. Early experience with remdesivir in SARS-CoV-2 pneumonia. Infection. 2020;48(5):779-782. PubMed, PubMedCentral, CrossRef
  8. Sternberg A, McKee DL, Naujokat C. Novel Drugs Targeting the SARS-CoV-2/COVID-19 Machinery. Curr Top Med Chem. 2020;20(16):1423-1433.
    PubMed, CrossRef
  9. World Health Organization. Coronavirus disease (COVID-19) pandemic. Last visit: 02/02/2022. https://www.who.int/emergencies/diseases/novel-coronavirus-2019.
  10. Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020;323(18):1824-1836. PubMed, CrossRef
  11. Sharma A, Mhatre M, Goldust M, Jindal V, Singla P. The COVID-19 chemoprophylactic conundrum: Are we limiting available resources? Dermatol Ther. 2020;33(4):e13607. PubMed, PubMedCentral, CrossRef
  12. Colson P, Rolain JM, Raoult D. Chloroquine for the 2019 novel coronavirus SARS-CoV-2. Int J Antimicrob Agents. 2020;55(3):105923. PubMed, PubMedCentral, CrossRef
  13. Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Sevestre J, Mailhe M, Doudier B, Aubry C, Amrane S, Seng P, Hocquart M, Eldin C, Finance J, Vieira VE, Tissot-Dupont HT, Honoré S, Stein A, Million M, Colson P, La Scola B, Veit V, Jacquier A, Deharo JC, Drancourt M, Fournier PE, Rolain JM, Brouqui P, Raoult D. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study. Travel Med Infect Dis. 2020;34:101663. PubMed, PubMedCentral, CrossRef
  14. Colson P, Rolain JM, Lagier JC, Brouqui P, Raoult D. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents. 2020;55(4):105932. PubMed, PubMedCentral, CrossRef
  15. Cortegiani A, Ingoglia G, Ippolito M, Giarratano A, Einav S. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care. 2020;57:279-283. PubMed, PubMedCentral, CrossRef
  16. Nieuwenhuijs-Moeke GJ, Jainandunsing JS, Struys MMRF. Sevoflurane, a sigh of relief in COVID-19? Br J Anaesth. 2020;125(2):118-121. PubMed, PubMedCentral, CrossRef
  17. Dong L, Hu S, Gao J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discov Ther. 2020;14(1):58-60. PubMed, CrossRef
  18. Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 2020;178:104787. PubMed, PubMedCentral, CrossRef
  19. 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 Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature. 2020;582(7811):289-293. PubMed, CrossRef
  20. Vidal-Albalat A, González FV. Natural Products as Cathepsin Inhibitors. Stud Nat Prod Chem. 2016;50:179–213. PubMedCentral, CrossRef
  21. Li YY, Fang J, Ao GZ. Cathepsin B and L inhibitors: a patent review (2010 – present). Expert Opin Ther Pat. 2017;27(6):643-656. PubMed, CrossRef
  22. Pubchem. Last visit: 07/16/2020. https://pubchem.ncbi.nlm.nih.gov/
  23. Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31(2):455-461. PubMed, PubMedCentral, CrossRef
  24. Swiss Institute of Bioinformatics. Last visit: 07/16/2020. SwissADME. http://www.swissadme.ch/index.php.
  25. Molinspiration. Last visit: 07/16/2020. https://www.molinspiration.com/
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