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. 2020 Oct-Dec;12(4):246-250.

Effective Anti-SARS-CoV-2 RNA Dependent RNA Polymerase Drugs Based on Docking Methods: The Case of Milbemycin, Ivermectin, and Baloxavir Marboxil

Ali Hassan Daghir Janabi  1
Affiliations

Effective Anti-SARS-CoV-2 RNA Dependent RNA Polymerase Drugs Based on Docking Methods: The Case of Milbemycin, Ivermectin, and Baloxavir Marboxil

Ali Hassan Daghir Janabi. Avicenna J Med Biotechnol. 2020 Oct-Dec.

Abstract

Background: Severe Acute Respiratory Syndrome-coronavirus 2 (SARS-CoV-2) is a new virus with a global pandemic. Yet, no vaccine or efficient treatments are found against the disease. The viral RNA dependent RNA Polymerase (RdRP) is a suitable target for developing antiviral agents. SARS-CoV-2 RdRP was employed to test its binding activity with some drugs.

Methods: Using some docking methods, RdRP was targeted by Milbemycins (MMs), Ivermectin (IMT), Baloxavir Marboxil (BM), and Tadalafil (TF), a phosphodiesterase type 5 inhibitor.

Results: MM-A3 5-oxime (MMA35O), MM-A3 (MMA3), MM-A4 5-oxime (MMA45O), IMT, BM, and TF showed the highest binding affinity to RdRp.

Conclusion: The drugs used in the present computational investigation are effective against the SARS-CoV-2 RdRP with high affinity values especially, milbemycins, ivermectin, and Baloxavir marboxil, which could further be studied in laboratory and clinical trials for saving millions of lives around the world.

Keywords: Baloxavir; COVID-19; Ivermectin; Tadalafil.

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Figures

Figure 1.
Figure 1.
Chemical structures of the study ligands.
Figure 2.
Figure 2.
RNA dependent RNA polymerase (grey, surface-hydrophobicity mode) of the SARS-CoV-2 (COVID-19) in complex with different ligand drugs (red); A) MMA35O binds to the B motif; B) MMA3 binds to the F motif; C) MMA45O binds to the B and F motifs; D) IMT binds to the C and F motifs; E) BM binds to the B and F motifs; F) TF binds to the B and F motifs.
Figure 3.
Figure 3.
Zoom-in images of the RNA dependent RNA polymerase (grey) of the SARS-CoV-2 (COVID-19) with different ligand drugs (cyan); A) MMA35O binds to the B motif; B) MMA3 binds to the F motif; C) MMA45O binds to the B and F motifs; D) IMT binds to the C and F motifs; E) BM binds to the B and F motifs; F) TF binds to the B and F motifs.
Figure 4.
Figure 4.
Interactions (3D-model) of ligands with the RNA dependent RNA polymerase of the SARS-CoV-2 (COVID-19) based on hydrogen bond style visualized by Discovery Studio Visualizer v20.1.0. 19295; A) MMA35O; B) MMA3; C) MMA45O; D) IMT; E) BM; F) TF.
Figure 5.
Figure 5.
Interactions (2D-model) of ligands with the RNA dependent RNA polymerase of the SARS-CoV-2 (COVID-19) based on hydrogen bond style visualized by Discovery Studio Visualizer v20.1.0.19295; A) MMA35O; B) MMA3; C) MMA45O; D) IMT; E) BM; F) TF.
See this image and copyright information in PMC

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