A Computational Study of Ivermectin and Doxycycline Combination Drug Against SARS-CoV-2 Infection
Dr Meenakshi Rana, Pooja Yadav, Papia Chowdhury
doi:10.21203/rs.3.rs-755838/v1
In the present study, we have described how by using molecular docking and molecular dynamics (MD) simulation studies the combination drug of ivermectin and doxycycline can be used as a potential inhibitor for Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) virus. In lieu of unavailability of specific cure of coronavirus disease of 2019 (COVID-19) till now various possibilities for individual and combination drugs have been explored by the medical practitioners/scientists for the remedial purpose of CoV-2 infections. 3C-like protease (3CL pro ) is the main protease of SARS-CoV-2 virus which plays an essential role in mediating viral replication in the human body. 3CL pro protein can serve as an attractive drug target. In this work, we have studied drug: 3CL pro interactions by in-silico molecular docking and MD simulation approaches. Common and easily available antiviral drugs ivermectin, doxycycline and their combination can regulate 3CL pro protein's function due to its easy inhibition.
docked pose position (Table 2 ). For doxycycline: protein complex, pose 7 is the better interacted position with the binding affinity of -6.4 kcal/mol, dreiding energy; 6,063.5, dipole moment; 6.104 Debye, inhibition constant; 2.0 X 10 -5 M and 7 number of hydrogen bonds (Table 2 ). Best pose of the donor-acceptor surface with their possible hydrogen bonding and hydrophobic interactions 3D and 2D view are shown in Figure 3b . Our result shows that out of two possible ligand drug structures, ivermectin represents the best potentiality to inhibit with the SARS 3CL pro (6LU7) by its best docking affinity compared to the doxycycline. Good binding mode of interactions of ivermectin: protein complex also verified by its less binding energy, minimum inhibition constant value as compared to doxycycline. Both the drug molecules showed good stability as a complex with the targeted protein. These drug molecules also satisfy the required drug likeness properties according to Ro5, Veber etc. rules, polar surface areas and logP values. RMSD corresponds to any change in the conformational stability of the protein: drug complex and in the protein dynamics. RMSD of the free protein and protein: ligand complex have been simulated to 100000 psby using MD simulations. RMSD and RMSF have been measured by using the GROMACS module at an interval of 1000 ps. RMSD variation of apo 3CL pro lies in the range from 0.08 to 0.16Å. Ivermectin: 3CL pro , doxycycline: 3CL pro , ivermectin+doxycycline: 3CL..
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'(SARS-CoV) virus. In lieu of unavailability of specific cure of coronavirus disease of 2019 '
'(COVID-19) till now various possibilities for individual and combination drugs have been '
'explored by the medical practitioners/scientists for the remedial purpose of CoV-2 '
'infections. 3C-like protease (3CL<jats:sup>pro</jats:sup>) is the main protease of SARS-CoV-2 '
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'3CL<jats:sup>pro</jats:sup> protein can serve as an attractive drug target. In this work, we '
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'<jats:italic>in-silico</jats:italic> molecular docking and MD simulation approaches. Common '
'and easily available antiviral drugs ivermectin, doxycycline and their combination can '
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