Introduction: The development of potent antiviral drugs against COVID-19 is of utmost
importance. In this context, computational pharmacology may play a lead role. This study
aimed on in-silico screening of Sri Lankan natural products by molecular docking (MD) and
molecular dynamics studies against SARS-CoV-2 main protease Mpro responsible for
multiplication.
Objective: To identify plant-derived compounds of Sri Lankan flora as antiviral agents with
protease inhibitory potential against SARS-CoV-2 pandemic.
Methods: Four hundred & eighty molecules isolated from Sri Lankan natural resources were
virtually screened for anti-viral activities against SARS-CoV-2 main protease Mpro. Binding
energies were calculated using Auto Dock Vina and the active site of SARS-CoV-2 was
defined using data from literature studies. The results were compared with that of a synthetic
construct of N3, a peptidomimetic inhibitor of coronavirus main protease. The complexes with
favorable binding interactions were filtered and subjected to molecular dynamic studies using
AMBER with GPU acceleration where the dynamic behavior of protein-ligand complex at
different time scales was determined. Visual Molecular Dynamic (VMD, version 1.9.4) was
used to study the atom trajectories and the Root Mean Square Deviation (RMSD) of each of
the protein ligand complex. The RMSD of the SARS-CoV-2 and drug complex was analyzed
through a 100ns trajectory and results were compared with that of N3. Further, the ADME
parameters, pharmacokinetic properties and the druglike nature of identified compounds were
studied.
Results: One of the natural products, SLNP_012, showed favorable interactions with the
binding pocket of Mpro as compared to that of N3. SLNP_012 showed up to 5 possible H-bond
with the active site residues. It also showed favorable physiochemical properties for oral bio
availability with a very high gastrointestinal absorption and blood brain barrier permeation.
Conclusions: Sri Lankan plant derive natural product SLNP_012 could be a potential anti-viral
agent for SARS-CoV-2 infection
Introduction: The development of potent antiviral drugs against COVID-19 is of utmost
importance. In this context, computational pharmacology may play a lead role. This study
aimed on in-silico screening of Sri Lankan natural products by molecular docking (MD) and
molecular dynamics studies against SARS-CoV-2 main protease Mpro responsible for
multiplication.
Objective: To identify plant-derived compounds of Sri Lankan flora as antiviral agents with
protease inhibitory potential against SARS-CoV-2 pandemic.
Methods: Four hundred & eighty molecules isolated from Sri Lankan natural resources were
virtually screened for anti-viral activities against SARS-CoV-2 main protease Mpro. Binding
energies were calculated using Auto Dock Vina and the active site of SARS-CoV-2 was
defined using data from literature studies. The results were compared with that of a synthetic
construct of N3, a peptidomimetic inhibitor of coronavirus main protease. The complexes with
favorable binding interactions were filtered and subjected to molecular dynamic studies using
AMBER with GPU acceleration where the dynamic behavior of protein-ligand complex at
different time scales was determined. Visual Molecular Dynamic (VMD, version 1.9.4) was
used to study the atom trajectories and the Root Mean Square Deviation (RMSD) of each of
the protein ligand complex. The RMSD of the SARS-CoV-2 and drug complex was analyzed
through a 100ns trajectory and results were compared with that of N3. Further, the ADME
parameters, pharmacokinetic properties and the druglike nature of identified compounds were
studied.
Results: One of the natural products, SLNP_012, showed favorable interactions with the
binding pocket of Mpro as compared to that of N3. SLNP_012 showed up to 5 possible H-bond
with the active site residues. It also showed favorable physiochemical properties for oral bio
availability with a very high gastrointestinal absorption and blood brain barrier permeation.
Conclusions: Sri Lankan plant derive natural product SLNP_012 could be a potential anti-viral
agent for SARS-CoV-2 infection
