7aeg - Revision history

OCA at 12:08, 1 February 2024

OCA — Thu, 01 Feb 2024 12:08:02 GMT

←Older revision		Revision as of 12:08, 1 February 2024
Line 3:		Line 3:
	<StructureSection load='7aeg' size='340' side='right'caption='[[7aeg]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='7aeg' size='340' side='right'caption='[[7aeg]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7aeg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~2019-ncov 2019-ncov~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AEG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AEG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7aeg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AEG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AEG FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>~~</td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.7Å</td></tr>
-	<tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=CF0:FLUOROMETHANE'>CF0</scene>, <scene name='pdbligand=~~PHQ~~:~~BENZYL~~+~~CHLOROCARBONATE~~'>~~PHQ~~</scene>~~</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CF0:FLUOROMETHANE'>CF0</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=PHQ:BENZYL+CHLOROCARBONATE'>PHQ</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">rep~~, ~~1a-1b ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2697049 2019-nCoV])~~<~~/td></tr>~~	+
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b></td><td class="sblockDat"><span class='plainlinks~~'>~~[https://en.wikipedia.org/wiki/SARS_coronavirus_main_proteinase SARS coronavirus main proteinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.69 3.4.22.69]~~ </~~span~~></td></tr>	+
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7aeg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aeg OCA], [https://pdbe.org/7aeg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aeg RCSB], [https://www.ebi.ac.uk/pdbsum/7aeg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aeg ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7aeg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aeg OCA], [https://pdbe.org/7aeg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aeg RCSB], [https://www.ebi.ac.uk/pdbsum/7aeg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aeg ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/R1AB_SARS2 R1AB_SARS2]] Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein.[UniProtKB:P0C6X7] Inhibits host translation by interacting with the 40S ribosomal subunit. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. Viral mRNAs are not susceptible to nsp1-mediated endonucleolytic RNA cleavage thanks to the presence of a 5'-end leader sequence and are therefore protected from degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response.[UniProtKB:P0C6X7] May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2. Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses.[UniProtKB:P0C6X7] Responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Participates together with nsp4 in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3. Prevents also host NF-kappa-B signaling.[UniProtKB:P0C6X7] Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication.[UniProtKB:P0C6X7] Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN] (PubMed:32198291). Also able to bind an ADP-ribose-1''-phosphate (ADRP).[UniProtKB:P0C6X7]<ref>PMID:32198291</ref> Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic. Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes.[UniProtKB:P0C6X7] Forms a hexadecamer with nsp8 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.[UniProtKB:P0C6X7] Forms a hexadecamer with nsp7 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.[UniProtKB:P0C6X7] May participate in viral replication by acting as a ssRNA-binding protein.[UniProtKB:P0C6X7] Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase activities. Therefore plays an essential role in viral mRNAs cap methylation.[UniProtKB:P0C6X7] Responsible for replication and transcription of the viral RNA genome.[UniProtKB:P0C6X7] Multi-functional protein with a zinc-binding domain in N-terminus displaying RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Activity of helicase is dependent on magnesium.[UniProtKB:P0C6X7] Enzyme possessing two different activities: an exoribonuclease activity acting on both ssRNA and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase activity. Acts as a proofreading exoribonuclease for RNA replication, thereby lowering The sensitivity of the virus to RNA mutagens.[UniProtKB:P0C6X7] Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.[UniProtKB:P0C6X7] Methyltransferase that mediates mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral mRNAs. N7-methyl guanosine cap is a prerequisite for binding of nsp16. Therefore plays an essential role in viral mRNAs cap methylation which is essential to evade immune system.[UniProtKB:P0C6X7]	+	[https://www.uniprot.org/uniprot/R1AB_SARS2 R1AB_SARS2] Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein.[UniProtKB:P0C6X7] Inhibits host translation by interacting with the 40S ribosomal subunit. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. Viral mRNAs are not susceptible to nsp1-mediated endonucleolytic RNA cleavage thanks to the presence of a 5'-end leader sequence and are therefore protected from degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response.[UniProtKB:P0C6X7] May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2. Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses.[UniProtKB:P0C6X7] Responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Participates together with nsp4 in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3. Prevents also host NF-kappa-B signaling.[UniProtKB:P0C6X7] Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication.[UniProtKB:P0C6X7] Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN] (PubMed:32198291). Also able to bind an ADP-ribose-1''-phosphate (ADRP).[UniProtKB:P0C6X7]<ref>PMID:32198291</ref> Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic. Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes.[UniProtKB:P0C6X7] Forms a hexadecamer with nsp8 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.[UniProtKB:P0C6X7] Forms a hexadecamer with nsp7 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.[UniProtKB:P0C6X7] May participate in viral replication by acting as a ssRNA-binding protein.[UniProtKB:P0C6X7] Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase activities. Therefore plays an essential role in viral mRNAs cap methylation.[UniProtKB:P0C6X7] Responsible for replication and transcription of the viral RNA genome.[UniProtKB:P0C6X7] Multi-functional protein with a zinc-binding domain in N-terminus displaying RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Activity of helicase is dependent on magnesium.[UniProtKB:P0C6X7] Enzyme possessing two different activities: an exoribonuclease activity acting on both ssRNA and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase activity. Acts as a proofreading exoribonuclease for RNA replication, thereby lowering The sensitivity of the virus to RNA mutagens.[UniProtKB:P0C6X7] Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.[UniProtKB:P0C6X7] Methyltransferase that mediates mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral mRNAs. N7-methyl guanosine cap is a prerequisite for binding of nsp16. Therefore plays an essential role in viral mRNAs cap methylation which is essential to evade immune system.[UniProtKB:P0C6X7]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: 2019-ncov]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~SARS~~ coronavirus ~~main proteinase~~]]	+	[[Category: Severe acute respiratory syndrome coronavirus 2]]
-	[[Category: ~~Brewitz, L~~]]	+	[[Category: Synthetic construct]]
-	[[Category: ~~Collette, A~~]]	+	[[Category: Brewitz L]]
-	[[Category: ~~Collins, P~~]]	+	[[Category: Collette A]]
-	[[Category: ~~Delft, F von~~]]	+	[[Category: Collins P]]
-	[[Category: Douangamath, A]]	+	[[Category: Douangamath A]]
-	[[Category: Fearon, D]]	+	[[Category: Fearon D]]
-	[[Category: Hallet, D]]	+	[[Category: Hallet D]]
-	[[Category: Hopkins~~, A L~~]]	+	[[Category: Hopkins AL]]
-	[[Category: Hull, H]]	+	[[Category: Hull H]]
-	[[Category: Lukacik, P]]	+	[[Category: Lukacik P]]
-	[[Category: Malla~~, T R~~]]	+	[[Category: Malla TR]]
-	[[Category: Navratilova, I]]	+	[[Category: Navratilova I]]
-	[[Category: Nugen, T]]	+	[[Category: Nugen T]]
-	[[Category: Owen~~, C D~~]]	+	[[Category: Owen CD]]
-	[[Category: Radoux, C]]	+	[[Category: Radoux C]]
-	[[Category: Redhead~~, M A~~]]	+	[[Category: Redhead MA]]
-	[[Category: Robinson, C]]	+	[[Category: Robinson C]]
-	[[Category: Schofield~~, C J~~]]	+	[[Category: Schofield CJ]]
-	[[Category: Strain-Damerell, C]]	+	[[Category: Strain-Damerell C]]
-	[[Category: Stuart~~, D I~~]]	+	[[Category: Stuart DI]]
-	[[Category: Tumber, A]]	+	[[Category: Tumber A]]
-	[[Category: Walsh~~, M A~~]]	+	[[Category: Walsh MA]]
-	[[Category: ~~Covid-19]]~~	+	[[Category: Von Delft F]]
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Protease]]~~	+
-	~~[[Category: Viral protein~~]]	+

OCA at 06:28, 25 August 2021

OCA — Wed, 25 Aug 2021 06:28:36 GMT

←Older revision		Revision as of 06:28, 25 August 2021
Line 1:		Line 1:

	==SARS-CoV-2 main protease in a covalent complex with SDZ 224015 derivative, compound 5==		==SARS-CoV-2 main protease in a covalent complex with SDZ 224015 derivative, compound 5==
-	<StructureSection load='7aeg' size='340' side='right'caption='[[7aeg]]' scene=''>	+	<StructureSection load='7aeg' size='340' side='right'caption='[[7aeg]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AEG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AEG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7aeg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/2019-ncov 2019-ncov]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AEG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AEG FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7aeg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aeg OCA], [https://pdbe.org/7aeg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aeg RCSB], [https://www.ebi.ac.uk/pdbsum/7aeg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aeg ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CF0:FLUOROMETHANE'>CF0</scene>, <scene name='pdbligand=PHQ:BENZYL+CHLOROCARBONATE'>PHQ</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">rep, 1a-1b ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2697049 2019-nCoV])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/SARS_coronavirus_main_proteinase SARS coronavirus main proteinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.69 3.4.22.69] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7aeg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aeg OCA], [https://pdbe.org/7aeg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aeg RCSB], [https://www.ebi.ac.uk/pdbsum/7aeg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aeg ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/R1AB_SARS2 R1AB_SARS2]] Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein.[UniProtKB:P0C6X7] Inhibits host translation by interacting with the 40S ribosomal subunit. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. Viral mRNAs are not susceptible to nsp1-mediated endonucleolytic RNA cleavage thanks to the presence of a 5'-end leader sequence and are therefore protected from degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response.[UniProtKB:P0C6X7] May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2. Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses.[UniProtKB:P0C6X7] Responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Participates together with nsp4 in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3. Prevents also host NF-kappa-B signaling.[UniProtKB:P0C6X7] Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication.[UniProtKB:P0C6X7] Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN] (PubMed:32198291). Also able to bind an ADP-ribose-1''-phosphate (ADRP).[UniProtKB:P0C6X7]<ref>PMID:32198291</ref> Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic. Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes.[UniProtKB:P0C6X7] Forms a hexadecamer with nsp8 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.[UniProtKB:P0C6X7] Forms a hexadecamer with nsp7 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.[UniProtKB:P0C6X7] May participate in viral replication by acting as a ssRNA-binding protein.[UniProtKB:P0C6X7] Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase activities. Therefore plays an essential role in viral mRNAs cap methylation.[UniProtKB:P0C6X7] Responsible for replication and transcription of the viral RNA genome.[UniProtKB:P0C6X7] Multi-functional protein with a zinc-binding domain in N-terminus displaying RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Activity of helicase is dependent on magnesium.[UniProtKB:P0C6X7] Enzyme possessing two different activities: an exoribonuclease activity acting on both ssRNA and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase activity. Acts as a proofreading exoribonuclease for RNA replication, thereby lowering The sensitivity of the virus to RNA mutagens.[UniProtKB:P0C6X7] Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.[UniProtKB:P0C6X7] Methyltransferase that mediates mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral mRNAs. N7-methyl guanosine cap is a prerequisite for binding of nsp16. Therefore plays an essential role in viral mRNAs cap methylation which is essential to evade immune system.[UniProtKB:P0C6X7]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Effective agents to treat coronavirus infection are urgently required, not only to treat COVID-19, but to prepare for future outbreaks. Repurposed anti-virals such as remdesivir and human anti-inflammatories such as barcitinib have received emergency approval but their overall benefits remain unclear. Vaccines are the most promising prospect for COVID-19, but will need to be redeveloped for any future coronavirus outbreak. Protecting against future outbreaks requires the identification of targets that are conserved between coronavirus strains and amenable to drug discovery. Two such targets are the main protease (M(pro)) and the papain-like protease (PL(pro)) which are essential for the coronavirus replication cycle. We describe the discovery of two non-antiviral therapeutic agents, the caspase-1 inhibitor SDZ 224015 and Tarloxotinib that target M(pro) and PL(pro), respectively. These were identified through extensive experimental screens of the drug repurposing ReFRAME library of 12,000 therapeutic agents. The caspase-1 inhibitor SDZ 224015, was found to be a potent irreversible inhibitor of M(pro) (IC50 30 nM) while Tarloxotinib, a clinical stage epidermal growth factor receptor inhibitor, is a sub micromolar inhibitor of PL(pro) (IC50 300 nM, Ki 200 nM) and is the first reported PL(pro) inhibitor with drug-like properties. SDZ 224015 and Tarloxotinib have both undergone safety evaluation in humans and hence are candidates for COVID-19 clinical evaluation.
		+
		+	Bispecific repurposed medicines targeting the viral and immunological arms of COVID-19.,Redhead MA, Owen CD, Brewitz L, Collette AH, Lukacik P, Strain-Damerell C, Robinson SW, Collins PM, Schafer P, Swindells M, Radoux CJ, Hopkins IN, Fearon D, Douangamath A, von Delft F, Malla TR, Vangeel L, Vercruysse T, Thibaut J, Leyssen P, Nguyen TT, Hull M, Tumber A, Hallett DJ, Schofield CJ, Stuart DI, Hopkins AL, Walsh MA Sci Rep. 2021 Jun 24;11(1):13208. doi: 10.1038/s41598-021-92416-4. PMID:34168183<ref>PMID:34168183</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7aeg" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: 2019-ncov]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Brewitz L]]	+	[[Category: SARS coronavirus main proteinase]]
-	[[Category: Collette A]]	+	[[Category: Brewitz, L]]
-	[[Category: Collins P]]	+	[[Category: Collette, A]]
-	[[Category: Douangamath A]]	+	[[Category: Collins, P]]
-	[[Category: Fearon D]]	+	[[Category: Delft, F von]]
-	[[Category: Hallet D]]	+	[[Category: Douangamath, A]]
-	[[Category: Hopkins AL]]	+	[[Category: Fearon, D]]
-	[[Category: Hull H]]	+	[[Category: Hallet, D]]
-	[[Category: Lukacik P]]	+	[[Category: Hopkins, A L]]
-	[[Category: Malla TR]]	+	[[Category: Hull, H]]
-	[[Category: Navratilova I]]	+	[[Category: Lukacik, P]]
-	[[Category: Nugen T]]	+	[[Category: Malla, T R]]
-	[[Category: Owen CD]]	+	[[Category: Navratilova, I]]
-	[[Category: Radoux C]]	+	[[Category: Nugen, T]]
-	[[Category: Redhead MA]]	+	[[Category: Owen, C D]]
-	[[Category: Robinson C]]	+	[[Category: Radoux, C]]
-	[[Category: Schofield CJ]]	+	[[Category: Redhead, M A]]
-	[[Category: Strain-Damerell C]]	+	[[Category: Robinson, C]]
-	[[Category: Stuart DI]]	+	[[Category: Schofield, C J]]
-	[[Category: Tumber A]]	+	[[Category: Strain-Damerell, C]]
-	[[Category: Walsh MA]]	+	[[Category: Stuart, D I]]
-	[[Category: ~~Von Delft F~~]]	+	[[Category: Tumber, A]]
		+	[[Category: Walsh, M A]]
		+	[[Category: Covid-19]]
		+	[[Category: Inhibitor]]
		+	[[Category: Protease]]
		+	[[Category: Viral protein]]

OCA at 09:54, 7 July 2021

OCA — Wed, 07 Jul 2021 09:54:26 GMT

←Older revision		Revision as of 09:54, 7 July 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7aeg is ~~ON HOLD until Paper Publication~~	+	==SARS-CoV-2 main protease in a covalent complex with SDZ 224015 derivative, compound 5==
-		+	<StructureSection load='7aeg' size='340' side='right'caption='[[7aeg]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AEG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AEG FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7aeg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aeg OCA], [https://pdbe.org/7aeg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aeg RCSB], [https://www.ebi.ac.uk/pdbsum/7aeg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aeg ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Brewitz L]]
		+	[[Category: Collette A]]
		+	[[Category: Collins P]]
		+	[[Category: Douangamath A]]
		+	[[Category: Fearon D]]
		+	[[Category: Hallet D]]
		+	[[Category: Hopkins AL]]
		+	[[Category: Hull H]]
		+	[[Category: Lukacik P]]
		+	[[Category: Malla TR]]
		+	[[Category: Navratilova I]]
		+	[[Category: Nugen T]]
		+	[[Category: Owen CD]]
		+	[[Category: Radoux C]]
		+	[[Category: Redhead MA]]
		+	[[Category: Robinson C]]
		+	[[Category: Schofield CJ]]
		+	[[Category: Strain-Damerell C]]
		+	[[Category: Stuart DI]]
		+	[[Category: Tumber A]]
		+	[[Category: Walsh MA]]
		+	[[Category: Von Delft F]]

OCA at 07:32, 24 December 2020

OCA — Thu, 24 Dec 2020 07:32:48 GMT

←Older revision		Revision as of 07:32, 24 December 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7aeg is ON HOLD	+	The entry 7aeg is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7aeg" [edit=sysop:move=sysop]

OCA — Wed, 23 Sep 2020 08:47:46 GMT

Protected "7aeg" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:47, 23 September 2020

OCA: New page: '''Unreleased structure''' The entry 7aeg is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 23 Sep 2020 08:47:44 GMT

New page: '''Unreleased structure''' The entry 7aeg is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7aeg is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]