Identification of Leading Compounds from Euphorbia neriifolia (Dudsor) Extracts as a Potential Inhibitor of SARS-CoV-2 ACE2-RBDS1 Receptor Complex: An Insight from Molecular Docking ADMET Profiling and MD-simulation Studies

Md Nur Islam; Md Enayet Ali Pramanik; Md Arju Hossain; Md Hasanur Rahman; Md Sahadot Hossen; Md Ashraful Islam; M Morsed Zaman Miah; Istiak Ahmed; Azm Mostaque Hossain; Md Jawadul Haque; Akm Monoarul Islam; Md Nowshad Ali; Rukhshana Akhter Jahan; Md Enamul Haque; Md Munzur Rahman; Md Sharif Hasan; Mohammad Motiur Rahman; Md Mamun Kabir; Prabir Mohan Basak; Md Abdul Mumit Sarkar; Md Shafiqul Islam; Md Rashedur Rahman; Akm Azad-Ud-Doula Prodhan; Ashik Mosaddik; Humayra Haque; Fahmida Fahmin; Haimanti Shukla Das; Md Manzurul Islam; Chandrima Emtia; Md Royhan Gofur; Aiping Liang; Sheikh Mohammad Fazle Akbar

doi:10.5005/jp-journals-10018-1414

Identification of Leading Compounds from Euphorbia neriifolia (Dudsor) Extracts as a Potential Inhibitor of SARS-CoV-2 ACE2-RBDS1 Receptor Complex: An Insight from Molecular Docking ADMET Profiling and MD-simulation Studies

Euroasian J Hepatogastroenterol. 2023 Jul-Dec;13(2):89-107. doi: 10.5005/jp-journals-10018-1414.

Authors

Md Nur Islam¹, Md Enayet Ali Pramanik², Md Arju Hossain³, Md Hasanur Rahman⁴, Md Sahadot Hossen⁵, Md Ashraful Islam⁶, M Morsed Zaman Miah⁷, Istiak Ahmed⁸, Azm Mostaque Hossain⁸, Md Jawadul Haque⁹, Akm Monoarul Islam¹⁰, Md Nowshad Ali¹¹, Rukhshana Akhter Jahan¹², Md Enamul Haque¹³, Md Munzur Rahman¹³, Md Sharif Hasan¹⁴, Mohammad Motiur Rahman¹⁵, Md Mamun Kabir¹⁵, Prabir Mohan Basak¹⁵, Md Abdul Mumit Sarkar¹⁶, Md Shafiqul Islam¹⁶, Md Rashedur Rahman¹⁷, Akm Azad-Ud-Doula Prodhan¹⁸, Ashik Mosaddik¹⁹, Humayra Haque²⁰, Fahmida Fahmin²¹, Haimanti Shukla Das²², Md Manzurul Islam²³, Chandrima Emtia²⁴, Md Royhan Gofur²⁵, Aiping Liang², Sheikh Mohammad Fazle Akbar²⁶

Affiliations

¹ National Laboratory of Biomacromolecules, Chinese Academy of Sciences Center for Excellence in Biomacromolecules, Institute of Biophysics; University of Chinese Academy of Sciences, Beijing, People's Republic of China.
² Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, College of Life Sciences, University of Chinese Academy of Sciences (UCAS), Beijing, People's Republic of China; On-Farm Research Division, Bangladesh Agricultural Research Institute, Rajshahi, Bangladesh.
³ Department of Biotechnology and Genetic Engineering, Mawlana Bhashani Science and Technology University, Santosh, Tangail, Bangladesh.
⁴ Department of Biotechnology and Genetic Engineering, Faculty of Life Sciences, Bangabandhu Sheikh Mujibur Rahman Science and Technology University (BSMRSTU), Gopalganj, Bangladesh.
⁵ Department of Biochemistry and Molecular Biology, School of Life Sciences, Shahjalal University of Science and Technology, Sylhet, Bangladesh.
⁶ Department of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
⁷ Department of Haematology, Rajshahi Medical College, Rajshahi, Bangladesh.
⁸ Department of Surgery, Rajshahi Medical College Hospital, Rajshahi, Bangladesh.
⁹ Department of Community Medicine, Rajshahi Medical College, Rajshahi, Bangladesh.
¹⁰ Department of Nephrology, Rajshahi Medical College, Rajshahi, Bangladesh.
¹¹ Department of Pediatric Surgery, Rajshahi Medical College, Rajshahi, Bangladesh.
¹² Department of Pathology, Rajshahi Medical College, Rajshahi, Bangladesh.
¹³ Department of Ortho-Surgery, Rajshahi Medical College, Rajshahi, Bangladesh.
¹⁴ Department of Cardiology, Mymensingh Medical College Hospital, Mymensingh, Bangladesh.
¹⁵ Department of Medicine, Rajshahi Medical College, Rajshahi, Bangladesh.
¹⁶ Department of Gastroenterology, Rajshahi Medical College, Rajshahi, Bangladesh.
¹⁷ Department of Agronomy, Bangladesh Agricultural University, Mymensingh, Bangladesh.
¹⁸ Department of Botany, Bangladesh Agricultural University, Mymensingh, Bangladesh.
¹⁹ Director, Center for Interdisciplinary Research, Varendra University, Rajshahi, Bangladesh.
²⁰ Department of Anaesthesia, Analgesia & Intensive Care Unit, Chattogram Medical College, Chattogram, Bangladesh.
²¹ Department of Paediatric, Mymensingh Medical College Hospital, Mymensingh, Bangladesh.
²² Department of Virology, Rajshahi Medical College, Rajshahi, Bangladesh.
²³ Director, Prime Minister Office and Private Secretary of Economic Advisor to the Hon'ble Prime Minister of Bangladesh, Prime Minister's Office, Tejgaon, Dhaka, Bangladesh.
²⁴ Laboratory of Systems Ecology, Faculty of Agriculture, Saga University, Honjo, Saga, Japan.
²⁵ Department of Veterinary and Animal Sciences, University of Rajshahi, Rajshahi, Bangladesh.
²⁶ Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine; Research Center for Global and Local Infectious Diseases, Faculty of Medicine, Oita University, Oita; Miyakawa Memorial Research Foundation, Tokyo, Japan.

Abstract

Coronavirus disease-19 (COVID-19) are deadly and infectious disease that impacts individuals in a variety of ways. Scientists have stepped up their attempts to find an antiviral drug that targets the spike protein (S) of Angiotensin converting enzyme 2 (ACE2) (receptor protein) as a viable therapeutic target for coronavirus. The most recent study examines the potential antagonistic effects of 17 phytochemicals present in the plant extraction of Euphorbia neriifolia on the anti-SARS-CoV-2 ACE2 protein. Computational techniques like molecular docking, absorption, distribution, metabolism, excretion, and toxicity (ADMET) investigations, and molecular dynamics (MD) simulation analysis were used to investigate the actions of these phytochemicals. The results of molecular docking studies showed that the control ligand (2-acetamido-2-deoxy-β-D-glucopyranose) had a binding potential of -6.2 kcal/mol, but the binding potentials of delphin, β-amyrin, and tulipanin are greater at -10.4, 10.0, and -9.6 kcal/mol. To verify their drug-likeness, the discovered hits were put via Lipinski filters and ADMET analysis. According to MD simulations of the complex run for 100 numbers, delphin binds to the SARS-CoV-2 ACE2 receptor's active region with good stability. In root-mean-square deviation (RMSD) and root mean square fluctuation (RMSF) calculations, delphinan, β-amyrin, and tulipanin showed reduced variance with the receptor binding domain subunit 1(RBD S1) ACE2 protein complex. The solvent accessible surface area (SASA), radius of gyration (Rg), molecular surface area (MolSA), and polar surface area (PSA) validation results for these three compounds were likewise encouraging. The convenient binding energies across the 100 numbers binding period were discovered by using molecular mechanics of generalized born and surface (MM/GBSA) to estimate the ligand-binding free energies to the protein receptor. All things considered, the information points to a greater likelihood of chemicals found in Euphorbia neriifolia binding to the SARS-CoV-2 ACE2 active site. To determine these lead compounds' anti-SARS-CoV-2 potential, in vitro and in vivo studies should be conducted.

How to cite this article: Islam MN, Pramanik MEA, Hossain MA, et al. Identification of Leading Compounds from Euphorbia Neriifolia (Dudsor) Extracts as a Potential Inhibitor of SARS-CoV-2 ACE2-RBDS1 Receptor Complex: An Insight from Molecular Docking ADMET Profiling and MD-simulation Studies. Euroasian J Hepato-Gastroenterol 2023;13(2):89-107.

Keywords: Absorption; Angiotensin converting enzyme 2; Coronavirus disease-19; Euphorbia neriifolia and phytochemicals; Molecular docking; Molecular dynamics simulation; Molecular mechanics of generalized born and surface; and toxicity (ADMET); distribution; excretion; metabolism.