The Ability of Secondary Metabolites from Actinomadura sp. as COVID-19 Protease Inhibitor: In Silico Method


  • Yuriza Eshananda Faculty of Biology, Universitas Jenderal Soedirman, Purwokerto, Central Java, Indonesia
  • Sri Martina Wiraswati Faculty of Biology, Universitas Jenderal Soedirman, Purwokerto, Central Java, Indonesia
  • Sri Lestari Faculty of Biology, Universitas Jenderal Soedirman, Purwokerto, Central Java, Indonesia
  • Afifah Mariana Faculty of Biology, Universitas Jenderal Soedirman, Purwokerto, Central Java, Indonesia
  • Tia Erfianti Faculty of Biology, Universitas Gadjah Mada, Yogyakarta, Indonesia
  • Hermin Pancasakti Kusumaningrum Biotechnology Study Program, Faculty of Natural Sciences and Mathematics, Universitas Diponegoro, Semarang, Central Java, Indonesia



Keywords: COVID-19 Protease, Actinomadura, Molecular Docking


The pandemic of COVID-19 disease in the late of 2019 resulted in the massive screening for drug discovery purpose. However, there is still no reports about the ability of natural products from bacterial group of class Actinobacteria as COVID-19 inhibitor. The aim of this research is to identify the potential ability of natural compounds from Actinomadura sp., the member of class Actinobacteria, against two receptors of COVID-19 protease with PDB ID 6LU7 and 5R7Y. The eleven natural compounds were docked using AutoDock Vina and the interaction between receptor and ligands were analysed using LIGPLOT. The most potential compound was simulated for its interaction stability using Yet Another Scientific Artificial Reality Application (YASARA) dynamics. The result of molecular docking by AutoDock Vina showed that Sagamilactam become the most potential inhibitor for viral protease as it had lower binding affinity (6LU7:-12 and 5R7Y:-10.4) compared to the both of  native ligand (6LU7:-11.4 and 5R7Y:-4.6). Furthermore, the interaction of the most potential ligand showed the low number of Root Mean Square Deviation (RMSD) deviation in molecular dynamic simulations. This result validated the docking method that used and indicated that secondary metabolites produced from rare actinobacteria of Actinomadura sp. have promising possibility to inhibit COVID-19 protease.


Download data is not yet available.


Aier, I., Varadwaj, P. K., & Raj, U. 2016. Structural insights into conformational stability of both wild-type and mutant EZH2 receptor. Scientific Reports, 6.

Al-Karmalawy, A. A., Dahab, M. A., Metwaly, A. M., Elhady, S. S., Elkaeed, E. B., Eissa, I. H., & Darwish, K. M. 2021. Molecular Docking and Dynamics Simulation Revealed the Potential Inhibitory Activity of ACEIs Against SARS-CoV-2 Targeting the hACE2 Receptor. Frontiers in Chemistry, 9.

Amin, D. H., Abdallah, N. A., Abolmaaty, A., Tolba, S., & Wellington, E. M. H. 2020. Microbiological and molecular insights on rare Actinobacteria harboring bioactive prospective. Bulletin of the National Research Centre, 44(1).

Azman, A. S., Othman, I., Velu, S. S., Chan, K. G., & Lee, L. H. 2015. Mangrove rare actinobacteria: Taxonomy, natural compound, and discovery of bioactivity. In Frontiers in Microbiology (Vol. 6, Issue AUG). Frontiers Media S.A.

Badji, B., Zitouni, A., Mathieu, F., Lebrihi, A., & Sabaou, N. 2006. Antimicrobial compounds produced by Actinomadura sp. AC104 isolated from an Algerian Saharan soil. Canadian Journal of Microbiology, 52(4), 373–382.

Case, D. A., Cheatham Iii, T. E., Darden, T., Gohlke, H., Luo, R., Merz, K. M., Onufriev, A., Simmerling, C., Wang, B., & Woods, R. J. 2015. The Amber Biomolecular Simulation Programs.

Ding, T., Yang, L. J., Zhang, W. D., & Shen, Y. H. 2019. The secondary metabolites of rare actinomycetes: Chemistry and bioactivity. In RSC Advances (Vol. 9, Issue 38, pp. 21964–21988). Royal Society of Chemistry.

Feikin, D. R., Higdon, M. M., Abu-Raddad, L. J., Andrews, N., Araos, R., Goldberg, Y., Groome, M. J., Huppert, A., O’Brien, K. L., Smith, P. G., Wilder-Smith, A., Zeger, S., Deloria Knoll, M., & Patel, M. K. 2022. Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: results of a systematic review and meta-regression. The Lancet, 399(10328), 924–944.

Glaser, J., Sedova, A., Galanie, S., Kneller, D. W., Davidson, R. B., Maradzike, E., del Galdo, S., Labbé, A., Hsu, D. J., Agarwal, R., Bykov, D., Tharrington, A., Parks, J. M., Smith, D. M. A., Daidone, I., Coates, L., Kovalevsky, A., & Smith, J. C. 2022. Hit Expansion of a Noncovalent SARS-CoV-2 Main Protease Inhibitor. ACS Pharmacology and Translational Science, 5(4), 255–265.

Huff, S., Kummetha, I. R., Tiwari, S. K., Huante, M. B., Clark, A. E., Wang, S., Bray, W., Smith, D., Carlin, A. F., Endsley, M., & Rana, T. M. 2022. Discovery and Mechanism of SARS-CoV-2 Main Protease Inhibitors. Journal of Medicinal Chemistry, 65(4), 2866–2879.

Ivanović, V., Rančić, M., Arsić, B., & Pavlović, A. 2020. Lipinski’s rule of five, famous extensions and famous exceptions. In POPULAR SCIENTIFIC ARTICLE (Vol. 3, Issue 1).

Kimura, T., Iwatsuki, M., Asami, Y., Ishiyama, A., Hokari, R., Otoguro, K., Matsumoto, A., Sato, N., Shiomi, K., Takahashi, Y., Omura, S., & Nakashima, T. 2016. Anti-trypanosomal compound, sagamilactam, a new polyene macrocyclic lactam from Actinomadura sp. K13-0306. Journal of Antibiotics, 69(11), 818–824.

Kony, D. B., Hünenberger, P. H., & van Gunsteren, W. F. 2007. Molecular dynamics simulations of the native and partially folded states of ubiquitin: Influence of methanol cosolvent, pH, and temperature on the protein structure and dynamics. Protein Science, 16(6), 1101–1118.

Krieger, E., & Vriend, G. 2015. New ways to boost molecular dynamics simulations. Journal of Computational Chemistry, 36(13), 996–1007.

Kusumaningrum, H. P., Ferniah, R. S., Jannah, S. N., Kurniawati, M. B., Afifah, A., Sumbodo, Y. M., Hanif, S. S., Erfianti, T., & Eshananda, Y. 2022. Relationship Between Phylogenetic of Apium and Foeniculum Plants from Central Java, Indonesia, and Their Secondary Metabolites Potency against COVID-19 Protease. Open Access Macedonian Journal of Medical Sciences, 10(A), 1234–1241.

Lipinski, C. A. 2004. Lead- and drug-like compounds: The rule-of-five revolution. In Drug Discovery Today: Technologies (Vol. 1, Issue 4, pp. 337–341).

Morris, G. M., Ruth, H., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S., & Olson, A. J. 2009. Software news and updates AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. Journal of Computational Chemistry, 30(16), 2785–2791.

Puttaswamy, H., Gowtham, H. G., Ojha, M. D., Yadav, A., Choudhir, G., Raguraman, V., Kongkham, B., Selvaraju, K., Shareef, S., Gehlot, P., Ahamed, F., & Chauhan, L. 2020. In silico studies evidenced the role of structurally diverse plant secondary metabolites in reducing SARS-CoV-2 pathogenesis. Scientific Reports, 10(1).

Ramadhan, D. S. F., Fakih, T. M., & Arfan, A. 2020. Activity Prediction of Bioactive Compounds Contained in Etlingera elatior Against the SARS-CoV-2 Main Protease: An In Silico Approach. Borneo Journal of Pharmacy, 3(4), 235–242.

Singhal, T. 2020. A Review of Coronavirus Disease-2019 (COVID-19). In Indian Journal of Pediatrics (Vol. 87, Issue 4, pp. 281–286). Springer.

Tarantini, F. S., Brunati, M., Taravella, A., Carrano, L., Parenti, F., Hong, K. W., Williams, P., Chan, K. G., Heeb, S., & Chan, W. C. 2021. Actinomadura graeca sp. nov.: A novel producer of the macrocyclic antibiotic zelkovamycin. PLoS ONE, 16(11).

Trott, O., & Olson, A. J. 2009. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, NA-NA.

Xue, Q., Liu, X., Russell, P., Li, J., Pan, W., Fu, J., & Zhang, A. 2022. Evaluation of the binding performance of flavonoids to estrogen receptor alpha by Autodock, Autodock Vina and Surflex-Dock. Ecotoxicology and Environmental Safety, 233.

Zeiger, E. 2019. The test that changed the world: The Ames test and the regulation of chemicals. In Mutation Research - Genetic Toxicology and Environmental Mutagenesis (Vol. 841, pp. 43–48). Elsevier B.V.

Zhang, L., Lin, D., Sun, X., Curth, U., Drosten, C., Sauerhering, L., Becker, S., Rox, K., & Hilgenfeld, R. 2020. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved a-ketoamide inhibitors. Science, 368(6489), 409–412.




How to Cite

Eshananda, Y., Wiraswati, S. M., Lestari, S. ., Mariana, A., Erfianti, T. and Kusumaningrum, H. P. (2023) “The Ability of Secondary Metabolites from Actinomadura sp. as COVID-19 Protease Inhibitor: In Silico Method”, Biotropic : The Journal of Tropical Biology, 7(2), pp. 25–34. doi: 10.29080/biotropic.v7i2.1926.