Abstract
COVID-19 has created a pandemic situation all over the world. It has spread in nearly every continent. Researchers all over the world are trying to produce an effective vaccine against this virus, however; no specific treatment for COVID-19 has been discovered -so far. The current work describes the inhibition study of the SARS-CoV-2 main proteinase or 3CL Mpro by natural and synthetic inhibitors, which include 2S albumin and flocculating protein from Moringa oleifera (M. oleifera) and Suramin. Molecular Docking study was carried out using the programs like AutoDock 4.0, HADDOCK2.4, patchdock, pardock, and firedock. The global binding energy of Suramin, 2S albumin, and flocculating proteins were −41.96, −9.12, and −14.78 kJ/mol, respectively. The docking analysis indicates that all three inhibitors bind at the junction of domains II and III. The catalytic function of 3CL Mpro is dependent on its dimeric form, and the flexibility of domain III is considered important for this dimerization. Our study showed that all three inhibitors reduce this flexibility and restrict their motion. The decrease in flexibility of domain III was further confirmed by analysis coming from Molecular dynamic simulation. The analysis results indicate that the temperature B-factor of the enzyme decreases tremendously when the inhibitors bind to it. This study will further explore the possibility of producing an effective treatment against COVID-19.
Highlights
A new virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in patients in China in December 2019 (Kotta et al, 2020)
The atomic coordinates of SARS-CoV-2 3CL main proteinase (Mpro), Suramin, and 2S albumin were retrieved from the Protein Data Bank (PDB), with PDB IDs: 6WQF (Kneller et al, 2020), 6CE2 (SVR) (Salvador et al, 2018), and 5DOM (Ullah et al, 2015)
The enzyme is active in the dimeric state and the flexibility of domain III is required for its dimerization (Kneller et al, 2020)
Summary
A new virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in patients in China in December 2019 (Kotta et al, 2020) It spread throughout the country and world quickly and infected millions of people all over the world (Kneller et al, 2020). The structure of this new virus is composed of single-stranded ribonucleic acid (RNA) and displays high sequence identity to other betacoronavirus such as SARS-CoV and MERS-CoV (Middle East respiratory syndrome coronavirus) (Cascella et al, 2020) These viruses use a specific protein named spike (S) protein to adhere to the angiotensin-converting enzyme (ACE2) on the host cell (Park et al, 2019; Turoòová et al, 2020). The current work has been designed to test the efficacy of natural and synthetic inhibitors (2S albumin and flocculating proteins of Moringa oleifera and Suramin), against 3CL Mpro and discover a new treatment for this pandemic disease
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