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

Ren, Zhilin; Yan, Liming; Zhang, Ning; Guo, Yu; Yang, Cheng; Lou, Zhiyong; Rao, Zihe

doi:10.1007/s13238-013-2841-3

Cited by 163 publications

(137 citation statements)

References 12 publications

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“…9) was identified to inhibit the proteolytic activity of MERS-CoV 3CL pro with an IC 50 of 0.28 mmol/L. The Xray crystal structure of MERS-CoV 3CL pro with inhibitor 55 confirms that inhibition of 3CL pro was similar to the mechanism to other CoVs [104], as the inhibitor binds with the interface of domain I and II of MERS-CoV 3CL pro with an EC 50 of about 0.3 mM [104].…”

Section: Mers-cov and Sars-cov Pl Proteases Inhibitorsmentioning

confidence: 77%

Recent discovery and development of inhibitors targeting coronaviruses

Pillaiyar

Meenakshisundaram²,

Manickam

2020

Drug Discovery Today

326

323

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Section: Mers-cov and Sars-cov Pl Proteases Inhibitorsmentioning

confidence: 77%

Recent discovery and development of inhibitors targeting coronaviruses

Pillaiyar

Meenakshisundaram²,

Manickam

2020

Drug Discovery Today

326

323

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“…Two crystal structures of the complex between the receptor-binding domain (RBD) of the MERS-CoV spike protein and DPP4 have been published very recently (Lu et al, 2013;Wang et al, 2013), as has the structure of the RBD alone (Chen et al, 2013a; see the review by F. Li, in this series). A crystal structure for the MERS-CoV main protease has also been communicated (Ren et al, 2013), and an article on the macrodomains of the virus by Lei et al is in preparation. All of these structures will be included in reviews in this series describing individual proteins of SARS-CoV and MERS-CoV.…”

Section: Ten Years After: Middle East Respiratory Syndrome Coronavirumentioning

confidence: 99%

From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses

2013

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This article introduces a series of invited papers in Antiviral Research marking the 10th anniversary of the outbreak of severe acute respiratory syndrome (SARS), caused by a novel coronavirus that emerged in southern China in late 2002. Until that time, coronaviruses had not been recognized as agents causing severe disease in humans, hence, the emergence of the SARS-CoV came as a complete surprise. Research during the past ten years has revealed the existence of a diverse pool of coronaviruses circulating among various bat species and other animals, suggesting that further introductions of highly pathogenic coronaviruses into the human population are not merely probable, but inevitable. The recent emergence of another coronavirus causing severe disease, Middle East respiratory syndrome (MERS), in humans, has made it clear that coronaviruses pose a major threat to human health, and that more research is urgently needed to elucidate their replication mechanisms, identify potential drug targets, and develop effective countermeasures. In this series, experts in many different aspects of coronavirus replication and disease will provide authoritative, up-to-date reviews of the following topics: - clinical management and infection control of SARS; - reservoir hosts of coronaviruses; - receptor recognition and cross-species transmission of SARS-CoV; - SARS-CoV evasion of innate immune responses; - structures and functions of individual coronaviral proteins; - anti-coronavirus drug discovery and development; and - the public health legacy of the SARS outbreak. Each article will be identified in the last line of its abstract as belonging to the series "From SARS to MERS: 10years of research on highly pathogenic human coronaviruses."

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“…While recent identification of the crystal structure of HCoV-EMC protease suggests that a wide-spectrum CoV protease inhibitor could block the catalytic site (12), there is currently no proven antiviral treatment for HCoV-EMC. Viruses rely on host factors to replicate and often hijack cellular processes initiated in response to infection to ensure efficient replication (13).…”

Section: Introductionmentioning

confidence: 99%

Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus

Josset

Menachery

Gralinski

et al. 2013

mBio

267

276

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A novel human coronavirus (HCoV-EMC) was recently identified in the Middle East as the causative agent of a severe acute respiratory syndrome (SARS) resembling the illness caused by SARS coronavirus (SARS-CoV). Although derived from the CoV family, the two viruses are genetically distinct and do not use the same receptor. Here, we investigated whether HCoV-EMC and SARS-CoV induce similar or distinct host responses after infection of a human lung epithelial cell line. HCoV-EMC was able to replicate as efficiently as SARS-CoV in Calu-3 cells and similarly induced minimal transcriptomic changes before 12 h postinfection. Later in infection, HCoV-EMC induced a massive dysregulation of the host transcriptome, to a much greater extent than SARS-CoV. Both viruses induced a similar activation of pattern recognition receptors and the interleukin 17 (IL-17) pathway, but HCoV-EMC specifically down-regulated the expression of several genes within the antigen presentation pathway, including both type I and II major histocompatibility complex (MHC) genes. This could have an important impact on the ability of the host to mount an adaptive host response. A unique set of 207 genes was dysregulated early and permanently throughout infection with HCoV-EMC, and was used in a computational screen to predict potential antiviral compounds, including kinase inhibitors and glucocorticoids. Overall, HCoV-EMC and SARS-CoV elicit distinct host gene expression responses, which might impact in vivo pathogenesis and could orient therapeutic strategies against that emergent virus.

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

Cited by 163 publications

References 12 publications

Recent discovery and development of inhibitors targeting coronaviruses

Recent discovery and development of inhibitors targeting coronaviruses

From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses

Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus

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