Phytocompounds as potential inhibitors of SARS-CoV-2 Mpro and PLpro through computational studies

Mithun Rudrapal; Ismail Celik; Sampath Chinnam; Mohammad Azam Ansari; Johra Khan; Saad Alghamdi; Mazen Almehmadi; James H Zothantluanga; Shubham J Khairnar

doi:10.1016/j.sjbs.2022.02.028

Phytocompounds as potential inhibitors of SARS-CoV-2 Mpro and PLpro through computational studies

Saudi J Biol Sci. 2022 May;29(5):3456-3465. doi: 10.1016/j.sjbs.2022.02.028. Epub 2022 Feb 25.

Authors

Mithun Rudrapal¹, Ismail Celik², Sampath Chinnam³, Mohammad Azam Ansari⁴, Johra Khan^{5

6}, Saad Alghamdi⁷, Mazen Almehmadi⁸, James H Zothantluanga⁹, Shubham J Khairnar¹⁰

Affiliations

¹ Department of Pharmaceutical Chemistry, Rasiklal M. Dhariwal Institute of Pharmaceutical Education & Research, Pune 411019, Maharashtra, India.
² Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Erciyes University, Kayseri 38280, Turkey.
³ Department of Chemistry, M. S. Ramaiah Institute of Technology (Affiliated to Visvesvaraya Technological University, Belgaum), Bengaluru 560054, Karnataka, India.
⁴ Department of Epidemic Disease Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia.
⁵ Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majmaah 11952, Saudi Arabia.
⁶ Health and Basic Sciences Research Center, Majmaah University, Al Majmaah 11952, Saudi Arabia.
⁷ Laboratory Medicine Department, Faculty of Applied Medical Sciences, Um Al-Qura University, Makkah 24382, Saudi Arabia.
⁸ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif 21944, Saudi Arabia.
⁹ Department of Pharmaceutical Sciences, Faculty of Science and Engineering, Dibrugarh University, Dibrugarh 786004, Assam, India.
¹⁰ MET Institute of Pharmacy, Bhujbal Knowledge City, Nasik 422003, Maharashtra, India.

Abstract

The inhibition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) and papain-like protease (PLpro) prevents viral multiplications; these viral enzymes have been recognized as one of the most favorable targets for drug discovery against SARS-CoV-2. In the present study, we screened 225 phytocompounds present in 28 different Indian spices to identify compounds as potential inhibitors of SARS-CoV-2 Mpro and PLpro. Molecular docking, molecular dynamics simulation, molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding free energy calculations, and absorption, distribution, metabolism, excretion and toxicity (ADMET) studies were done. Based on binding affinity, dynamics behavior, and binding free energies, the present study identifies pentaoxahexacyclo-dotriacontanonaen-trihydroxybenzoate derivative (PDT), rutin, and dihyroxy-oxan-phenyl-chromen-4-one derivative (DOC), luteolin-7-glucoside-4'-neohesperidoside as promising inhibitors of SARS-CoV-2 Mpro and PLpro, respectively.

Keywords: Molecular docking; Molecular dynamics; Mpro; PLpro; SARS-CoV-2; Spice phytochemicals.