The newly emerged SARS-Like coronavirus HCoV-EMC also has an “Achilles’ heel”: current effective inhibitor targeting a 3C-like protease

Emerging Infection Disease Program, High-throughput Molecular Drug Discovery Center, Tianjin Joint Academy of Biomedicine and Technology, Tianjin 300457, China Correspondence: raozh@xtal.tsinghua.edu.cnFrom the global outbreak of SARS-CoV caused infection disease in 2003, coronaviruses (CoVs) are known to be a great threat to the human health. Recently, a new SARS-like coronavirus, human betacoronavirus 2c EMC/2012 (HCoV-EMC), has been identified and the appearance of this new CoV raises concerns that a new spread of CoV may occurs in the future. By solving the crystal structure of HCoV-EMC main protease with a wide-spectrum anti-CoV inhibitor N3, we confi rmed that that N3 blocks the function of HCoV-EMC main protease through a similar mechanism to other CoVs. Together with the good pharmaceutical features, N3 is conceiv-able to be effective to HCoV-EMC and other CoVs appearing in the future. These fi ndings make it convincing that CoVs will not be a threat to human health.In the year of 2012, a new respira-tory illness similar to severe acute res-piratory syndrome (SARS) that spread globally in 2003 and infected over 8,000 people with more than 800 fatalities (Li et al., 2010), was identifi ed in Europe, the Middle East and Hong Kong. The infection was reported to manifest clini-cally with fever, cough and breathing dif-fi culties. Some patients also developed acute renal failure. Sequence analysis suggested that the causative agent of this newly emerged SARS-like illness is a new coronavirus (CoV) which has been named as the human betacorona-virus 2c EMC/2012 (HCoV-EMC). No clinically approved treatment is available for CoV infection since the outbreak of SARS in 2003, the appearance of this new CoV raises concerns that a new epidemic of CoV infection may occur in future.CoVs are positive-sense, single-stranded RNA viruses and are featured by the largest viral RNA genomes known to date (Yang et al., 2003). Rep-lication of coronavirus requires correct proteolytic processing of the replicase polyprotein by viral proteases, in particu-lar a chymotrypsin-like protease (3CL