Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has spread worldwide and caused widespread devastation. In the absence of definitive therapy, symptomatic management remains the standard of care. Repurposing of many existing drugs including several anti-viral drugs is being attempted to tackle the COVID-19 pandemic. However, most of them have failed to show significant benefit in clinical trials. An attractive approach may be to target host proteases involved in SARS-CoV-2 pathogenesis. The priming of the spike (S) protein of the virus by proteolytic cleavage by the trans-membrane serine protease-2 (TMPRSS2) is necessary for fusion of the virus to the host cell after it binds to its receptor angiotensin converting enzyme-2 (ACE2). There are other proteases with varying spatiotemporal locations that may be important for viral entry and subsequent replication inside the cells, and these include trypsin, furin and cathepsins. In this report, we discuss the tentative therapeutic role of inhibitors of TMPRSS2, cathepsin, trypsin, furin, plasmin, factor X and elastase in infection caused by SARS-CoV-2. Both available evidence as well as hypotheses are discussed, with emphasis on drugs which are approved for other indications such as bromhexine, ammonium chloride, nafamostat, camostat, tranexamic acid, epsilon amino-caproic acid, chloroquine, ulinastatin, aprotinin and anticoagulant drugs. Simultaneously, novel compounds being tested and problems with using these agents are also discussed.
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PMID:Targeting host cell proteases to prevent SARS-CoV-2 invasion. 3297 39

There are several families of cysteine proteinases with different folds - for example the (chymo)trypsin fold family and papain-like fold family - but in both families the hydrolase activity of cysteine proteinases requires a cysteine residue as the catalytic nucleophile. In this work, we have analyzed the topology of the active site regions in 146 three-dimensional structures of proteins belonging to the Papain-like Cysteine Proteinase (PCP) superfamily, which includes papain as a typical representative of this protein superfamily. All analyzed enzymes contain a unique structurally closed conformation - a "PCP-Zone" - which can be divided into two groups, Class A and Class B. Eight structurally conserved amino acids of the PCP-Zone form a common Structural Core. The Structural Core, catalytic nucleophile, catalytic base and residue Xaa - which stabilizes the side-chain conformation of the catalytic base - make up a PCP Structural Catalytic Core (PCP-SCC). The PCP-SCC of Class A and Class B are divided into 5 and 2 types, respectively. Seven variants of the mutual arrangement of the amino-acid side chains of the catalytic triad - nucleophile, base and residue Xaa - within the same fold clearly demonstrate how enzymes with the papain-like fold adapt to the need to perform diverse functions in spite of their limited structural diversity. The roles of both the PCP-Zone of SARS-CoV-2-PLpro described in this study and the NBCZone of SARS-CoV-2-3CLpro presented in our earlier article (Denesyuk AI, Johnson MS, Salo-Ahen OMH, Uversky VN, Denessiouk K. Int J Biol Macromol. 2020;153:399-411) that are in contacts with inhibitors are discussed.
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PMID:Papain-like cysteine proteinase zone (PCP-zone) and PCP structural catalytic core (PCP-SCC) of enzymes with cysteine proteinase fold. 3305 70

The coronavirus disease of 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which started in late 2019 in Wuhan, China spread to the whole world in a short period of time, and thousands of people have died due to this epidemic. Although scientists have been searching for methods to manage SARS-CoV-2, there is no specific medication against COVID-19 as of yet. Two main approaches should be followed in the treatment of SARS-CoV-2; one of which is to neutralize the virus, and the other is to inhibit the host cell membrane receptors, where SARS-CoV-2 will bind. In this study, peptides derived from beta-lactoglobulin, which inactivates both the virus and its receptors in the host cell, were identified using computer-based in silico analysis. The beta-lactoglobulin derived peptides used in this study were obtained by the treatment of goat milk whey fraction with trypsin. The structure of the peptides was characterized by the liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS), and six beta-lactoglobulin derived peptides were selected as candidate peptides. Subsequently, the effects of peptides on SARS-CoV-2 and host cells were identified using virtual screening. According to the results of this in silico analysis, Ala-Leu-Pro-Met-His-Ile-Arg (ALMPHIR) and Ile-Pro-Ala-Val-Phe-Lys (IPAVFK) peptides were evaluated as potential candidates to be used in the treatment of SARS-CoV-2 after the future in vitro and in vivo studies.
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PMID:Investigation of beta-lactoglobulin derived bioactive peptides against SARS-CoV-2 (COVID-19): In silico analysis. 3327 Nov 51


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