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Druggable targets of SARS-CoV-2 and treatment opportunities for COVID-19

Authors
  • Faheem,1
  • Kumar, Banoth Karan1
  • Sekhar, Kondapalli Venkata Gowri Chandra...2
  • Kunjiappan, Selvaraj3
  • Jamalis, Joazaizulfazli4
  • Balaña-Fouce, Rafael5
  • Tekwani, Babu L.6
  • Sankaranarayanan, Murugesan1
  • 1 Medicinal Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Vidya Vihar, Pilani 333031, Rajasthan, India
  • 2 Department of Chemistry, Birla Institute of Technology and Science Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet Mandal, R.R. Dist., Hyderabad, 500078 Telangana, India
  • 3 Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil 626126, TamilNadu, India
  • 4 Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia, Johor Bahru, Johor 81310, Malaysia
  • 5 Department of Biomedical Sciences, University of León, 24071 León, Spain
  • 6 Department of Infectious Diseases, Division of Drug Discovery, Southern Research, Birmingham, AL 35205, USA
Type
Published Article
Journal
Bioorganic Chemistry
Publisher
Elsevier Inc.
Publication Date
Sep 08, 2020
Volume
104
Pages
104269–104269
Identifiers
DOI: 10.1016/j.bioorg.2020.104269
PMID: 32947136
PMCID: PMC7476961
Source
PubMed Central
Keywords
License
Unknown

Abstract

COVID-19 caused by the novel SARS-CoV-2 has been declared a pandemic by the WHO is causing havoc across the entire world. As of May end, about 6 million people have been affected, and 367 166 have died from COVID-19. Recent studies suggest that the SARS-CoV-2 genome shares about 80% similarity with the SARS-CoV-1 while their protein RNA dependent RNA polymerase (RdRp) shares 96% sequence similarity. Remdesivir, an RdRp inhibitor, exhibited potent activity against SARS-CoV-2 in vitro . 3-Chymotrypsin like protease (also known as Mpro) and papain-like protease, have emerged as the potential therapeutic targets for drug discovery against coronaviruses owing to their crucial role in viral entry and host-cell invasion. Crystal structures of therapeutically important SARS-CoV-2 target proteins, namely, RdRp, Mpro, endoribonuclease Nsp15/NendoU and receptor binding domain of CoV-2 spike protein has been resolved, which have facilitated the structure-based design and discovery of new inhibitors. Furthermore, studies have indicated that the spike proteins of SARS-CoV-2 use the Angiotensin Converting Enzyme-2 (ACE-2) receptor for its attachment similar to SARS-CoV-1, which is followed by priming of spike protein by Transmembrane protease serine 2 (TMPRSS2) which can be targeted by a proven inhibitor of TMPRSS2, camostat. The current treatment strategy includes repurposing of existing drugs that were found to be effective against other RNA viruses like SARS, MERS, and Ebola. This review presents a critical analysis of druggable targets of SARS CoV-2, new drug discovery, development, and treatment opportunities for COVID-19.

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