Vol 13, Issue 9, 2020 Online - 2455-3891 Print - 0974-2441 MOLECULAR DOCKING STUDIES ON SCREENING AND ASSESSMENT OF SELECTED BIOFLAVONOIDS AS POTENTIAL INHIBITORS OF COVID-19 MAIN PROTEASE ABSTRACT Objectives: The objective of the study was to screen and assess the selected bioactive bioflavonoids in medicinal plants as potential coronaviruses (CoV) main protease (Mpro) inhibitors using molecular docking studies. Methods: We have investigated several bioflavonoids which include apigenin, galangin, glycitein, luteolin, morin, naringin, resveratrol, and rutin. Nelfinavir and lopinavir were used as standard antiviral drugs for comparison. Mpro was docked with selected compounds using PyRx 0.8 and docking was analyzed by PyRx 0.8 and Biovia Discovery Studio 2019. Results: The binding energies obtained from the docking of 6LU7 with native ligand, nelfinavir, lopinavir, apigenin, galangin, glycitein, luteolin, morin, naringin, resveratrol, and rutin were found to be −7.4, −8.3, −8.0, −7.8, −7.3, −7, −7.4, −7.6, −7.8, −6.9, and −9 kcal/mol, respectively. Conclusion: From the binding energy calculations, we can conclude that nelfinavir and lopinavir may represent potential treatment options and apigenin, galangin, glycitein, luteolin, morin, naringin, resveratrol, and rutin found to possess the best inhibitors of CoV disease-19 main protease. Keywords: Binding energy, 6LU7, Antiviral, Rutin, Coronavirus, Medicinal plants. INTRODUCTION The 2019-novel coronavirus (nCoV) is a major source of disaster in the 21 th century [1]. New CoV strain was identified in Wuhan, China, in the year 2019. CoVs are an infectious agent and found to cause serious diseases of respiratory tract and digestive tract [2]. The Emergency Committee of the World Health Organization declared an outbreak in China on January 30, 2020, which was considered as Public Health Emergencies of International Concern [3]. Officially, the WHO named this disease as CoV disease (COVID)-2019 on February 11, 2020 [4]. At present, no specific therapies for COVID-19 are available and investigations regarding the treatment of COVID-19 are lacking. Potential combinations of protease inhibitor lopinavir/ritonavir, which is commonly used to treat human immunodeficiency virus, for the treatment of COVID-19-infected patients have been investigated and reported. Furthermore, some other reported antiviral drugs such as remdesivir, umifenovir, tenofovir disoproxil, and lamivudine have been reported for COVID-19 [5]. The outbreaks of COVID-19 highlighted their adaptive potential to the changing environmental conditions and they are classified under “emerging viruses.” Knowledge about the structure, metabolic pathways of CoV, and pathophysiology of CoV-associated diseases is important to identify possible drug targets [6-9]. Liu et al. (2020) have successfully crystallized the main protease (Mpro) from COVID-19, which has been structured and repositioned in the Protein Data Bank (PDB) and is accessible by the public. This protease represents a potential target for the inhibition of CoV replication [10]. Flavonoids are the important class of plant secondary metabolites found to possess wide range of biological activities. These natural products were known for their beneficial effects on health long before flavonoids were isolated as the effective compounds [11]. Naturally occurring flavonoids with antiviral activity have been recognized since the 1940s and most of the work related with antiviral compounds revolves around inhibition of various enzymes associated with the life cycle of viruses [12]. Antiviral activity of apigenin, galangin, glycitein, luteolin, morin, naringin, resveratrol, and rutin has been reported in different studies [13-20]. Hence, these bioflavonoids were chosen for the present study. Literature search revealed that selected bioflavonoids have potent antiviral effect against different viruses and may be effective against COVID-19. Hence, there is a need of screening the selected bioflavonoids against molecular targets of COVID-19 using molecular docking techniques. No studies have been reported on molecular docking studies of selected bioflavonoids against selected target of COVID-19. This promoted us to carry out present research work. METHODS Standard drugs Nelfinavir and lopinavir were used as standard for comparison. Bioactive bioflavonoids Apigenin, galangin, glycitein, luteolin, morin, naringin, resveratrol, and rutin used as ligands. Software PyRx 0.8, Biovia Discovery Studio 2019, Molsoft, and MarvinSketch. Determination of drug-likeness properties of selected ligands In our study, we have selected bioflavonoids as ligands. To find out drug-like properties of each ligand, we have followed the Lipinski’s rule of five, which states that molecules with poor permeation and © 2020 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4. 0/) DOI: http://dx.doi.org/10.22159/ajpcr.2020.v13i9.38485 Research Article Received: 28 May 2020, Revised and Accepted: 16 July 2020 1Department of Pharmaceutical Chemistry, 2Department of Pharmacology, 3Department of Pharmacognosy and phytochemistry.KLE College of Pharmacy, Belagavi, KLE Academy of Higher Education and Research, Nehru Nagar, Belagavi, Karnataka, India. Email: shailendrasss80@gmail.com SHAILENDRA SANJAY SURYAWANSHI 1 *, POOJA BHAVAKANA JAYANNACHE 2 , RAJKUMAR SANJAY PATIL 2 , PALLED MS 1 , PRIYA SHETTI 3