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Structures of the Middle East respiratory syndrome coronavirus 3CL protease, an antiviral drug target

Friday, September 18, 2015 — Poster Session IV

12:00 p.m. – 1:30 p.m.
FAES Terrace


  • GT Lountos
  • D Needle
  • DS Waugh


The newly emerging and highly pathogenic Middle East Respiratory Syndrome Coronavirus (MERS- CoV) causes severe respiratory illness that is accompanied by multi-organ dysfunction, resulting in a case fatality rate of approximately 40%. Despite the alarmingly high mortality rate of the virus, there are no approved drugs available for the treatment of MERS. The majority of the positive-stranded RNA MERS-CoV genome is translated into two polyproteins, one created by a ribosomal frameshift, that are cleaved at three sites by a papain-like protease and at 11 sites by a 3C-like protease (3CLpro). Since the 3CLpro is essential for viral replication, it is a promising candidate for anti-viral drug design. To accelerate the development of 3CLpro inhibitors, we determined three crystal structures of a catalytically inactive variant (C148A) of the MERS-CoV 3CLpro: one of the free-enzyme and two structures representing enzyme-product complexes. Together, they illuminate the structural basis of substrate specificity and provide a starting point for structure-based drug design efforts to identify novel inhibitors.

Category: Structural Biology