Chalcones isolated from<i>Angelica keiskei</i>inhibit cysteine proteases of SARS-CoV

Park, Ji Young; Ko, Jin A.; Kim, Dae Wook; Kim, Young Min; Kwon, Hyung Jun; Jeong, Hyung Jae; Kim, Cha Young; Park, Ki Hun; Lee, Woo Song; Ryu, Young Bae

doi:10.3109/14756366.2014.1003215

Cited by 204 publications

(182 citation statements)

References 35 publications

(46 reference statements)

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“…One of the chalcones, compound 6 ( Fig. 7B), exhibited relatively strong inhibition of both the 3CL pro and the PL2 pro in vitro, with IC 50 values of 11.4 and 1.2 μM respectively (Park et al, 2016). Chalcone 6 uses different inhibition mechanisms for 3CL pro and PL2 pro .…”

Section: Papain-like Protease 2 (Pl2 Pro )mentioning

confidence: 98%

“…Recently, nine alkylated chalcones (1-9) and four coumarins (10-13), which were isolated from the perennial plant Angelica keiskei, had their inhibitory activities against both the SARS-CoV M pro (3CL pro , chymotrypsin-like protease) and the PL2 pro tested (Park et al, 2016). One of the chalcones, compound 6 ( Fig.…”

Section: Papain-like Protease 2 (Pl2 Pro )mentioning

confidence: 99%

“…Chalcone 6 uses different inhibition mechanisms for 3CL pro and PL2 pro . It is a competitive inhibitor for the former enzyme but a non-competitive one for the latter (Park et al, 2016). Clearly, the large body of structural information available for the CoV PL pro s and host DUBs should enable more design of inhibitors specific for the viral enzyme.…”

Section: Papain-like Protease 2 (Pl2 Pro )mentioning

confidence: 99%

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Nsp3 of coronaviruses: Structures and functions of a large multi-domain protein

2018

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The multi-domain non-structural protein 3 (Nsp3) is the largest protein encoded by the coronavirus (CoV) genome, with an average molecular mass of about 200 kD. Nsp3 is an essential component of the replication/transcription complex. It comprises various domains, the organization of which differs between CoV genera, due to duplication or absence of some domains. However, eight domains of Nsp3 exist in all known CoVs: the ubiquitin-like domain 1 (Ubl1), the Glu-rich acidic domain (also called "hypervariable region"), a macrodomain (also named "X domain"), the ubiquitin-like domain 2 (Ubl2), the papain-like protease 2 (PL2), the Nsp3 ectodomain (3Ecto, also called "zinc-finger domain"), as well as the domains Y1 and CoV-Y of unknown functions. In addition, the two transmembrane regions, TM1 and TM2, exist in all CoVs. The three-dimensional structures of domains in the N-terminal two thirds of Nsp3 have been investigated by X-ray crystallography and/or nuclear magnetic resonance (NMR) spectroscopy since the outbreaks of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) in 2003 as well as Middle-East Respiratory Syndrome coronavirus (MERS-CoV) in 2012. In this review, the structures and functions of these domains of Nsp3 are discussed in depth.

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Section: Papain-like Protease 2 (Pl2 Pro )mentioning

confidence: 98%

Section: Papain-like Protease 2 (Pl2 Pro )mentioning

confidence: 99%

Section: Papain-like Protease 2 (Pl2 Pro )mentioning

confidence: 99%

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Nsp3 of coronaviruses: Structures and functions of a large multi-domain protein

2018

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“…[40][41][42][43][44][45] However,a few low-nm-range inhibitors have been identified that can be used in combination with other protease-inhibitor therapies to help combat the virus. Many of the inhibitors are in the micromolar range in terms of binding to and inhibiting the two proteases.…”

Section: Rna-dependent Rna Polymerasementioning

confidence: 99%

“…In a FRET-baseda ctivity assay,t he IC 50 value of GC376a gainst recombinant SARS 3CLpro was found to be 4.9 times that against FIPV 3CLpro( 4.35 vs. 0.72 mm,r espectively). Arepresentation of the top CoV protease inhibitors providing ascaffold to perform SAR studies in termsofdesigning novel small-molecule protease inhibitors for 2019-nCoV [40][41][42][43][44][45]49] .3 CLpro-1, the most potent inhibitor,ish ighlighted. Figure 7.…”

Section: Rna-dependent Rna Polymerasementioning

confidence: 99%

Learning from the Past: Possible Urgent Prevention and Treatment Options for Severe Acute Respiratory Infections Caused by 2019‐nCoV

et al. 2020

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With the current trajectory of the 2019‐nCoV outbreak unknown, public health and medicinal measures will both be needed to contain spreading of the virus and to optimize patient outcomes. Although little is known about the virus, an examination of the genome sequence shows strong homology with its better‐studied cousin, SARS‐CoV. The spike protein used for host cell infection shows key nonsynonymous mutations that might hamper the efficacy of previously developed therapeutics but remains a viable target for the development of biologics and macrocyclic peptides. Other key drug targets, including RNA‐dependent RNA polymerase and coronavirus main proteinase (3CLpro), share a strikingly high (>95 %) homology to SARS‐CoV. Herein, we suggest four potential drug candidates (an ACE2‐based peptide, remdesivir, 3CLpro‐1 and a novel vinylsulfone protease inhibitor) that could be used to treat patients suffering with the 2019‐nCoV. We also summarize previous efforts into drugging these targets and hope to help in the development of broad‐spectrum anti‐coronaviral agents for future epidemics.

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