Potential Antiviral Mechanism of Hydroxychloroquine in COVID-19 and Further Extrapolation to Celecoxib (Celebrex) for Future Clinical Trials.
8 Pages Posted: 7 Apr 2020
Date Written: April 6, 2020
We are proposing a new hypothesis for the antiviral mechanism of hydroxychloroquine (HCQ), based on our computer aided docking studies. HCQ is a clinical trial drug under investigation for the treatment of COVID-19 pandemic. SARS-CoV-2 is the causative agent of the COVID-19 and it binds to host’s bromodomain proteins BRD-2/4. The bromodomain proteins are readers of acetylated histones and play a critical role for host’s hype-immune response to this pathogen. COVID-19 virus protein E mimics acetylated histones and binds at the same site on BRD-2. We propose that the hijacking of BRD-2/4 by SARS-CoV-2, can be thwarted by the use of inhibitors of BRD-2/4. Preliminary in-silico docking studies with HCQ, indicates that it binds to the same pocket on BRD-2 where viral envelope protein E binds. Therefore, HCQ may acts as a BRD-2 inhibitor, thereby preventing “cytokine storm” initiated by SARS-CoV-2 virus. Another FDA approved drug celecoxib (Celebrex) binds in the same pocket of BRD-2 and the key amino acid interactions between the drug and protein are conserved. Thus, celecoxib may offer innovative path for controlling the COVID-19 pandemic.
Note: Funding: This project was not funded by any agency.
Conflict of Interest: We do not have any competing interest declaration.
Keywords: COVID-19, Hydroxychloroquine, Celcoxib, BRD, Mechanism
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