In silico identification of potential inhibitors against main protease of SARS-CoV-2 6LU7 from Andrographis panniculata via molecular docking, binding energy calculations and molecular dynamics simulation studies

Mayakrishnan Vijayakumar; Balakarthikeyan Janani; Priya Kannappan; Senthil Renganathan; Sameer Al-Ghamdi; Mohammed Alsaidan; Mohamed A Abdelaziz; Abubucker Peer Mohideen; Mohammad Shahid; Thiyagarajan Ramesh

doi:10.1016/j.sjbs.2021.10.060

In silico identification of potential inhibitors against main protease of SARS-CoV-2 6LU7 from Andrographis panniculata via molecular docking, binding energy calculations and molecular dynamics simulation studies

Saudi J Biol Sci. 2022 Jan;29(1):18-29. doi: 10.1016/j.sjbs.2021.10.060. Epub 2021 Oct 29.

Affiliations

¹ Laboratory of Cell and Molecular Biology, Grassland and Forage Science Division, National Institute of Animal Science, Rural Development Administration, Cheonan-si, Chungcheongnam-do 31000, Republic of Korea.
² Department of Biochemistry, PSG College of Arts and Science (Autonomous), Affiliated to Bharathiar University, Coimbatore 641014, Tamil Nadu, India.
³ Department of Bioinformatics, Marudupandiyar College, Thanjavur 613 403, Tamil Nadu, India.
⁴ Lysine Biotech Private Limited, Periyar Technology Incubator, DST Business Incubator, Periyar Maniammai Institute of Science and Technology (PMIST), Vallam, Thanjavur 613403, Tamil Nadu, India.
⁵ Family and Community Medicine Department, College of Medicine, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Kingdom of Saudi Arabia.
⁶ Internal Medicine Department, College of Medicine, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Kingdom of Saudi Arabia.
⁷ Department of Basic Medical Sciences, College of Medicine, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Kingdom of Saudi Arabia.
⁸ Department of Medical Physiology, College of Medicine, Al-Azhar University, Cairo, Egypt.

Abstract

Background: The ongoing global outbreak of new corona virus (SARS-CoV-2) has been recognized as global public health concern since it causes high morbidity and mortality every day. Due to the rapid spreading and re-emerging, we need to find a potent drug against SARS-CoV-2. Synthetic drugs, such as hydroxychloroquine, remdisivir have paid more attention and the effects of these drugs are still under investigation, due to their severe side effects. Therefore, the aim of the present study was performed to identify the potential inhibitor against main protease SARS-CoV-2 6LU7.

Objective: In this study, RO5, ADME properties, molecular dynamic simulations and free binding energy prediction were mainly investigated.

Results: The molecular docking study findings revealed that andrographolide had higher binding affinity among the selected natural diterpenoids compared to co-crystal native ligand inhibitor N3. The persistent inhibition of Ki for diterpenoids was analogous. Furthermore, the simulations of molecular dynamics and free binding energy findings have shown that andrographolide possesses a large amount of dynamic properties such as stability, flexibility and binding energy.

Conclusion: In conclusion, findings of the current study suggest that selected diterpenoids were predicted to be the significant phytonutrient-based inhibitor against SARS-CoV-2 6LU7 (M^pro). However, preclinical and clinical trials are needed for the further scientific validation before use.

Keywords: ACE 2, Angiotensin Converting Enzyme; Andrographolide; CNS, central nervous system; COVID-19 (6LU7); COVID-19, coronavirus disease 2019; Corona; Diterpenoids; Molecular dynamic simulations; Mpro, Main protease; Natural compounds; SARS-CoV-2; SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2.