scholarly journals A Combination of Ivermectin and Doxycycline Possibly Blocks the Viral Entry and Modulate the Innate Immune Response in COVID-19 Patients

2020 ◽  
Author(s):  
Dharmendra Kumar Maurya
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Binding Affinity ◽  
Viral Entry ◽  
Virus Disease ◽  
Host Cells ◽  
Dynamics Simulation ◽  
Host Immune System ◽  
Main Protease ◽  
Approved Drugs

<p></p><p>The current outbreak of the corona virus disease 2019 (COVID-19), has affected almost entire world and become pandemic now. Currently, there is neither any FDA approved drugs nor any vaccines available to control it. Very recently in Bangladesh, a group of doctors reported astounding success in treating patients suffering from COVID-19 with two commonly used drugs, Ivermectin and Doxycycline. In the current study we have explored the possible mechanism by which these drugs might have worked for the positive response in the COVID-19 patients. To explore the mechanism we have used molecular docking and molecular dynamics simulation approach. Effectiveness of Ivermectin and doxycycline were evaluated against Main Protease (Mpro), Spike (S) protein, Nucleocapsid (N), RNA-dependent RNA polymerase (RdRp, NSP12), ADP Ribose Phosphatase (NSP3), Endoribonuclease (NSP15) and methyltransferase (NSP10-NSP16 complex) of SARS-CoV-2 as well as human angiotensin converting enzyme 2 (ACE2) receptor. Our study shows that both Ivermectin and doxycycline have significantly bind with SARS-CoV-2 proteins but Ivermectin was better binding than doxycycline. Ivermectin showed a perfect binding site to the Spike-RBD and ACE2 interacting region indicating that it might be interfering in the interaction of spike with ACE2 and preventing the viral entry in to the host cells. Ivermectin also exhibited significant binding affinity with different SARS-CoV-2 structural and non-structural proteins (NSPs) which have diverse functions in virus life cycle. Significant binding of Ivermectin with RdRp indicate its role in the inhibition of the viral replication and ultimately impeding the multiplication of the virus. Ivermectin also possess significant binding affinity with NSP3, NSP10, NSP15 and NSP16 which helps virus in escaping from host immune system. Molecular dynamics simulation study shows that binding of the Ivermectin with Mpro, Spike, NSP3, NSP16 and ACE2 was quiet stable. Thus, our docking and simulation studies reveal that combination of Ivermectin and doxycycline might be executing the effect by inhibition of viral entry and enhance viral load clearance by targeting various viral functional proteins.</p><p></p>

scholarly journals A Combination of Ivermectin and Doxycycline Possibly Blocks the Viral Entry and Modulate the Innate Immune Response in COVID-19 Patients

2020 ◽  
Author(s):  
Dharmendra Kumar Maurya
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Binding Affinity ◽  
Viral Entry ◽  
Virus Disease ◽  
Host Cells ◽  
Dynamics Simulation ◽  
Host Immune System ◽  
Main Protease ◽  
Approved Drugs

<p></p><p>The current outbreak of the corona virus disease 2019 (COVID-19), has affected almost entire world and become pandemic now. Currently, there is neither any FDA approved drugs nor any vaccines available to control it. Very recently in Bangladesh, a group of doctors reported astounding success in treating patients suffering from COVID-19 with two commonly used drugs, Ivermectin and Doxycycline. In the current study we have explored the possible mechanism by which these drugs might have worked for the positive response in the COVID-19 patients. To explore the mechanism we have used molecular docking and molecular dynamics simulation approach. Effectiveness of Ivermectin and doxycycline were evaluated against Main Protease (Mpro), Spike (S) protein, Nucleocapsid (N), RNA-dependent RNA polymerase (RdRp, NSP12), ADP Ribose Phosphatase (NSP3), Endoribonuclease (NSP15) and methyltransferase (NSP10-NSP16 complex) of SARS-CoV-2 as well as human angiotensin converting enzyme 2 (ACE2) receptor. Our study shows that both Ivermectin and doxycycline have significantly bind with SARS-CoV-2 proteins but Ivermectin was better binding than doxycycline. Ivermectin showed a perfect binding site to the Spike-RBD and ACE2 interacting region indicating that it might be interfering in the interaction of spike with ACE2 and preventing the viral entry in to the host cells. Ivermectin also exhibited significant binding affinity with different SARS-CoV-2 structural and non-structural proteins (NSPs) which have diverse functions in virus life cycle. Significant binding of Ivermectin with RdRp indicate its role in the inhibition of the viral replication and ultimately impeding the multiplication of the virus. Ivermectin also possess significant binding affinity with NSP3, NSP10, NSP15 and NSP16 which helps virus in escaping from host immune system. Molecular dynamics simulation study shows that binding of the Ivermectin with Mpro, Spike, NSP3, NSP16 and ACE2 was quiet stable. Thus, our docking and simulation studies reveal that combination of Ivermectin and doxycycline might be executing the effect by inhibition of viral entry and enhance viral load clearance by targeting various viral functional proteins.</p><p></p>

scholarly journals Molecular Docking and Molecular Dynamics Simulation Studies of Triterpenes from Vernonia patula with the Cannabinoid Type 1 Receptor

2021 ◽  
Vol 22 (7) ◽  
pp. 3595
Author(s):  
Md Afjalus Afjalus Siraj ◽  
Md. Sajjadur Rahman ◽  
Ghee T. Tan ◽  
Veronique Seidel
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulation ◽  
Binding Affinity ◽  
Docking Studies ◽  
Dynamics Simulation ◽  
Simulation Studies ◽  
Cannabinoid Type 1 Receptor ◽  
Docking Approach

A molecular docking approach was employed to evaluate the binding affinity of six triterpenes, namely epifriedelanol, friedelin, α-amyrin, α-amyrin acetate, β-amyrin acetate, and bauerenyl acetate, towards the cannabinoid type 1 receptor (CB1). Molecular docking studies showed that friedelin, α-amyrin, and epifriedelanol had the strongest binding affinity towards CB1. Molecular dynamics simulation studies revealed that friedelin and α-amyrin engaged in stable non-bonding interactions by binding to a pocket close to the active site on the surface of the CB1 target protein. The studied triterpenes showed a good capacity to penetrate the blood–brain barrier. These results help to provide some evidence to justify, at least in part, the previously reported antinociceptive and sedative properties of Vernonia patula.

scholarly journals Effects of the Temperature and the pH on the Main Protease of SARS-CoV-2: A Molecular Dynamics Simulation Study

2021 ◽  
Vol 12 (6) ◽  
pp. 7239-7248
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Root Mean Square ◽  
Dynamics Simulation ◽  
Effect Of Temperature ◽  
Water Molecules ◽  
Mean Square ◽  
Main Protease ◽  
Decreasing Ph ◽  
Increasing Temperature

The novel coronavirus, recognized as COVID-19, is the cause of an infection outbreak in December 2019. The effect of temperature and pH changes on the main protease of SARS-CoV-2 were investigated using all-atom molecular dynamics simulation. The obtained results from the root mean square deviation (RMSD) and root mean square fluctuations (RMSF) analyses showed that at a constant temperature of 25℃ and pH=5, the conformational change of the main protease is more significant than that of pH=6 and 7. Also, by increasing temperature from 25℃ to 55℃ at constant pH=7, a remarkable change in protein structure was observed. The radial probability of water molecules around the main protease was decreased by increasing temperature and decreasing pH. The weakening of the binding energy between the main protease and water molecules due to the increasing temperature and decreasing pH has reduced the number of hydrogen bonds between the main protease and water molecules. Finding conditions that alter the conformation of the main protease could be fundamental because this change could affect the virus’s functionality and its ability to impose illness.

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