Journal of Clinical and Cellular Immunology
Open Access
ISSN: 2155-9899
ISSN: 2155-9899
Aim: In search of an effective treatment for COVID-19 disease, in Bangladesh, a group of doctors reported surprising success with two commonly used drugs, Ivermectin and Doxycycline. But the mechanism underlying therapeutic action of these drugs remains obscure. The current study explores the possible molecular targets and mechanism of action.
Methods: Structure of both Ivermectin and Doxycycline were optimized using universal forcefield as well as by quantum mechanics. Molecular docking and molecular dynamics simulation techniques were employed to explore the possible mechanism of action of these drugs. Effectiveness of Ivermectin and Doxycycline was evaluated against several proteins of SARS-CoV-2 and human ACE2 receptor.
Results: It was found that both the drugs have significant binding affinity with SARS-CoV-2 proteins as evinced from low predicted binding energy. Ivermectin showed better binding than Doxycycline. Ivermectin showed a perfect binding to the site of interaction between Spike-RBD and ACE2 proteins indicating that it might be interfering with the viral entry in to the host cells. It also exhibited significant binding affinity with different SARSCoV- 2 structural and non-structural proteins which have diverse functions in virus life cycle. Our study also shows that Ivermectin has lower binding affinity to spike protein of omicron variant compared with wild-type. Significant binding of Ivermectin with RdRp indicated its role in the inhibition of the viral replication and ultimately impeding the multiplication of the virus. Ivermectin also showed significant binding affinity with the proteins which help the virus in escaping from host immune system. Molecular dynamics study well corroborates with molecular docking and showed that binding of Ivermectin with Mpro, Spike, NSP3, NSP16 and ACE2 are stable.
Significance: This study predicts that the combination of Ivermectin and Doxycycline might be executing the therapeutic effect by inhibition of viral entry, moderation of viral multiplication and improving the viral clearance.
Published Date: 2024-07-18; Received Date: 2023-08-23