International Journal of Pharma and Bio Sciences
 
 
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ORIGINAL RESEARCH ARTICLE
Int J Pharm Bio Sci Volume 12 Issue 2, 2021 (April-June), Pages:78-85

Molecular Docking study to Identify Potent Fungal Metabolites as Inhibitors against SARS-CoV-2 Main Protease Enzyme

Dr Diptendu Sarkar
DOI: http://dx.doi.org/10.22376/ijpbs.2021.12.2.b78-85
Abstract:

Severe acute respiratory syndrome (SARS) is a viral respiratory disease caused by a SARS-associated coronavirus and SARS-CoV-2 has proven to be a pandemic worldwide. Coronaviruses are a type of enveloped virus. They are basically single-stranded and positive-sense RNA viruses which belongs to the subfamily Coronavirinae. Structure of SARS-CoV-2 is predicted to be the same as SARS-CoV due to high sequence similarity. SARS-CoV-2 is proven to be a major pandemic creator and affected the world at an exponential rate. The genome of COVID19 codes for the main protease 6LU7, is essential for viral replication and multiplication. To get a possible antiviral drug(s), nowadays is the major concern. In our study we screened ten fungal metabolites such as Aspirochlorine, Aflatoxin B1, Alpha-Cyclopiazonic acid, Sporogen, Asperfuran, Aspergillomarasmine A, Maltoryzine, Kojic acid, Aflatrem and Ethyl 3-nitropropionic acid against main protease 6LU7. These molecules were of fungal origin from Aspergillus flavus and Aspergillus oryzae. Aspergillomarasmine A exhibited the docking score of – 6.02 Kcal/mol, almost nearer to presently used drug Chloroquine (-6.29 Kcal/mol). Second highest docking score was found for Asperfuran (-5.5 Kcal/mol), whereas Aflatoxin B1 provided docking score was -5.0 Kcal/mol. We found similar docking score -5.4 Kcal/mol for Asperfuran, Maltoryzine and Kojic acid. Aspirochlorine and Ethyl 3-nitropropionic acid exhibited docking score were -5.3 Kcal/mol and -5.1 Kcal/mol respectively. These natural bioactive compounds could be tested in near future for their ability to inhibit viral growth both in invitro as well as invivo study.

Keywords: SARS-CoV-2, Main Protease Enzyme 6LU7, Aspirochlorine, Aflatoxin B1, Alpha-Cyclopiazonic acid, Sporogen, Asperfuran, Aspergillomarasmine A, Maltoryzine, Kojic acid, Aflatrem.
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Reference

1.       Anthony RF, Stanley P. Coronavirus: an overview of their replication and pathogenesis. Methods Mol Biol. 2015;1282:1-23. doi: 10.1007/978-1-4939-2438-7_1.

2.       Shereen MA, Khan S, Kazmi A, Bashir N, Siddique R. COVID-19 infection: origin, transmission, and characteristics of human coronaviruses. J Adv Res. 2020;24:91-8. doi: 10.1016/j.jare.2020.03.005, PMID 32257431.

3.       Gao K, Nguyen DD, Wang R, Wei GW. Machine intelligence design of 2019- nCoV drugs. bioRxiv. 2020. doi: 10.1101/2020.01.30.927889, PMID 32511308.

4.       Raj VS, Mou H, Smits SL, Dekkers DH, Müller MA, Dijkman R, Muth D, Demmers JA, Zaki A, Fouchier RA, Thiel V, Drosten C, Rottier PJ, Osterhaus AD, Bosch BJ, Haagmans BL. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature. 2013;495(7440):251-4. doi: 10.1038/nature12005, PMID 23486063.

5.       Zhong N, Zheng B, Li Y, Poon L, Xie Z, Chan K, Li P, Tan S, Chang Q, Xie J, Liu X, Xu J, Li D, Yuen K, Peiris J, Guan Y. Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People’s Republic of China, in February, 2003. Lancet. 2003;362(9393):1353-8. doi: 10.1016/S0140-6736(03)14630-2.

6.       Wang N, Shi X, Jiang L, Zhang S, Wang D, Tong P, et al. Structure of MERS-CoV spikereceptor-binding domain complexed with human receptor DPP4. Cell Res. 2013;23(8):986-93.org. doi: 10.1038/CR.2013.92, PMID 23835475.

7.       Cui J, Li F, Shi ZL. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol. 2019;17(3):181-92. doi: 10.1038/s41579-018-0118-9, PMID 30531947.

8.       Lai CC, Shih TP, Ko WC, Tang HJ, Hsueh PR. Severe acute respiratory syndromecoronavirus 2 (SARS-CoV-2) and corona virus disease-2019 (COVID-19): the epidemic and the challenges. Int J Antimicrob Agents. 2020;55(3):105924. doi: 10.1016/j.ijantimicag.2020.105924.

9.       Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. Lancet. 2020;395(10223):470-3. doi: 10.1016/S0140-6736(20)30185-9.

10.     Nagata N, Iwata N, Hasegawa H, Fukushi S, Yokoyama M, Harashima A, Sato Y, Saijo M, Morikawa S, Sata T. Participation of both host and virus factors in induction of severe acute respiratory syndrome (SARS) in F344 rats infected with SARS coronavirus. J Virol. 2007;81(4):1848-57. doi: 10.1128/JVI.01967-06, PMID 17151094.

11.     Christian A, Devaux JMR, Philippe C, Didier R. New insight on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicrob Agents. 2020. doi: 1016/j.ijantimicag.2020.105938.

12.     de Azevedo WF Jr. Docking screens for drug discovery. Vol. 2053. ISBN: 978-1-4939-9751-0; 2019.

13.     Fearon D, Powell AJ, Douangamath A, Owen CD, Wild C, Krojer T, Lukacik P, Strain-Damerell CM, Walsh MA, von Delft F. Crystal Structure of COVID-19 main protease in complex with Z18197050; 2020. doi: 10.2210/pdb5R80/pdb.

14.     Jorgensen WL, Maxwell DS, Tirado-Rives JT. Development and testing of the OPLS All-atom force field on conformational energetic and properties of organic liquids. J Am Chem Soc. 1996;118(45):11225-36. doi: 10.1021/ja9621760.15.     Meng XY, Zhang HX, Mezei M, Cui M. Molecular docking: a powerful approach for structure-based drug discovery. Curr Comput Aided Drug Des. 2011;7(2):146-57. doi: 10.21

74/157340911795677602, PMID 21534921.

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):409-12. doi: 10.1126/science.abb3405, PMID 32198291.

17.     Xue X, Yu H, 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):2515-27. doi: 10.1128/JVI.02114-07, PMID 18094151.

18.     Li Y, Zhang J, Wang N, Li H, Shi Y, Guo G, Liu K, Zeng H, Zou Q. Therapeutic drugs targeting 2019-nCoV main protease by high-throughput screening. bioRxiv. 2020. doi: 10.1101/2020.01.28.922922.

19.     Glowacka I, Bertram S, Müller MA, Allen P, Soilleux E, Pfefferle S, Steffen I, Tsegaye TS, He Y, Gnirss K, Niemeyer D, Schneider H, Drosten C, Pöhlmann S. Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response. J Virol. 2011;85(9):4122-34. doi: 10.1128/JVI.02232-10, PMID 21325420.

20.     Bertram S, Glowacka I, Müller MA, Lavender H, Gnirss K, Nehlmeier I, Niemeyer D, He Y, Simmons G, Drosten C, Soilleux EJ, Jahn O, Steffen I, Pöhlmann S. Cleavage and activation of the severe acute respiratory syndrome coronavirus spike protein by human airway trypsin-like protease. J Virol. 2011;85(24):13363-72. doi: 10.1128/JVI.05300-11, PMID 21994442.

21.     Son SY, Sunmin Lee S, Digar, Singh, D., Na-Rae Lee. Front Microbiol, D-Y and Lee, C-H. 2018. Comprehensive Secondary Metabolite Profiling Toward Delineating the Solid and Submerged-State Fermentation of Aspergillus oryzae KCCM 12698;9:1-12. doi: 10.3389/fmicb.2018.01076.

22.     Sakata K, Toshiaki K, Akira S, Nobutaka, T, Gakuzo T. Isolation of Aspirochlorine (=Antibiotic A30641) as a true antimicrobial constituent of the antibiotic, Oryzachlorin, from Aspergillus oryzae. Agric. BioI. Chem. 1983;47(11):2673-4. doi: 10.1080/00021369.1983.10866014.

23.     Klausmeyer P, McCloud TG, Tucker KD, Cardellina JH, Shoemaker RH. Aspirochlorine class compounds from Aspergillus flavus inhibit azole-resistant Candida albicans. J Nat Prod. 2005;68(8):1300-2. doi: 10.1021/np050141k, PMID 16124785.

24.     Neda S, 2020. Molecular docking study of novel COVID-19 protease with low risk terpenoides compounds of plants. ChemRxiv [preprint]. doi: 10.26434/chemrxiv.11935722.v1.

25.     Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019- nCoV) in vitro. Cell Res. 2020;30(3). 1-3. doi: 10.1038/s41422-020-0282-0, PMID 32020029.

26.     Wang BX, Fish EN. Global virus outbreaks: interferons as 1st responders. Semin Immunol. 2019;43:101300. doi: 10.1016/j.smim.2019.101300.

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