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Potential antiviral mechanism of hydroxychloroquine in COVID-19 and further extrapolation to celecoxib (Celebrex) for future clinical trials.
  • Fallbackprofileimagethumb
  • Rahul Khupse,
  • Pankaj Dixit
Rahul Khupse
University of Findlay, College of Pharmacy, Findlay, OH, USA-43551)
Author Profile
Pankaj Dixit
Department of Pharmacology, Indore Institute of Pharmacy, Indore, Rau-Pithampur Road 453331 (M.P.) India

Abstract

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. Preliminaryin-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.