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Mite allergens
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2020
Enrique Fernández-Caldas, Leonardo Puerta, Luis Caraballo, Victor Iraola, Richard F. Lockey
Blo t 1, homologous to Der p 1, is a cysteine protease. Blo t 1, with an estimated molecular weight of 26 kDa, is an important allergen. Recombinant Blo t 1 reacted positively with IgE in 90% and 65% of sera from asthmatic children and adults from Singapore, respectively. Furthermore, there is a low correlation between IgE reactivity to Blo t 1 and Der p 1 [21]. Recently, the crystal structure of recombinant Blo t 1 was determined and indicated a fold characteristic for the pro-form of cysteine proteases from the C1A class. Structural comparison of experimentally mapped Der f 1/Der p1 IgG epitopes to the same surface patch on Blo t 1, and the sequence identity of surface-exposed residues, suggests limited cross-reactivity between these allergens and Blo t 1 [22].
Potential Significance of Proteases
Published in Hafiz Ansar Rasul Suleria, Megh R. Goyal, Masood Sadiq Butt, Phytochemicals from Medicinal Plants, 2019
Marwa Waheed, Muhammad Bilal Hussain, Sadia Hassan, Mohammad Ali Shariati, Oluwafemi Adeleke Ojo
Proteases were recognized from the sap or latex of various families of plants, for example, apocynaceae, asteraceae, moraceae, euphorbiaceae, and caricaceae. Most of the plant proteases have been categorized as cysteine protease and aspartic proteases. Numerous industrialized processes include protein breakdown by proteases and some of the proteases are obtained from plants. Protein modification by enzymatic proteolysis can improve functional properties of protein isolates and also used in the production of special food, which are destined for children, the old people, or sportsmen. Medicinal seeds were also reported for their proteolytic activity and these seeds are used to treat different diseases. Proteases have been used in the processing of rennet or chymosin for cheese making where, chymosin breaks the specific peptide bond.79
Programmed Cell Death: The Biology of Cell Death in the Nematode Caenorhabditis elegans and Implications for the Understanding and Treatment of Human Brain Injury after Cardiac Surgery
Published in Richard A. Jonas, Jane W. Newburger, Joseph J. Volpe, John W. Kirklin, Brain Injury and Pediatric Cardiac Surgery, 2019
These observations strongly suggest that the CED-3 protein causes programmed cell death in C. elegans by acting as a cysteine protease, presumably either by activating other killer proteins or by inactivating proteins that protect cells from dying. These observations also suggest that members of the CED-3/ICE family of cysteine proteases, perhaps even ICE itself, might function in causing programmed cell death in other organisms, including humans. This hypothesis has been strongly supported by the findings that expression of either ced-3 or ICE in rat fibroblasts can cause these cells to undergo apoptotic cell death15 and that a viral protein inhibitor of ICE, crmA, can block the apoptotic death of chick dorsal root ganglion cells that have been deprived of nerve growth factor.16 Thus, a CED-3/ICE-like cysteine protease can cause mammalian cell death, and an inhibitor of such a protease can block a normal pathway of vertebrate cell death, indicating that an endogenous protease of this class functions in this pathway.
Drugs repurposing for SARS-CoV-2: new insight of COVID-19 druggability
Published in Expert Review of Anti-infective Therapy, 2022
Sujit Kumar Debnath, Monalisha Debnath, Rohit Srivastava, Abdelwahab Omri
This library also suggested some cysteine protease inhibitors like ONO 5334, VBY-825, ZLVG CHN2, and MDL-28170. Out of them, ONO 5334, VBY-825, and MDL 28170 are more potent against SARS-CoV-2. MDL-28170 is a cathepsin B inhibitor. Previously, this drug eradicated the infection caused by the Ebola virus and SARS-CoV. VBY-825 is a reversible cathepsin protease inhibitor, and ONO 5334 acts as a cathepsin K inhibitor. Human cysteinyl cathepsins are essential during infection for proteolytic processing of virally encoded proteins. Proper processing of S-protein is required to activate fusogenic activity where cathepsin activity is needed. The antiviral activity of MDL 28170 and ONO 5334 was evaluated in human induced pluripotent stem cells infected with SARS-CoV-2. Both drugs significantly reduced viral replication by 72% by ONO 5334 and 65% by MDL 28170 [106].
A patent review on cathepsin K inhibitors to treat osteoporosis (2011 – 2021)
Published in Expert Opinion on Therapeutic Patents, 2022
Fernanda R. Rocho, Vinícius Bonatto, Rafael F. Lameiro, Jerônimo Lameira, Andrei Leitão, Carlos A. Montanari
Worthy of note is the successful application of cysteine protease inhibitors to treat viral diseases. Recently, the Food and Drug Administration has approved Paxlovid, a combination drug that has the inhibitors Nirmatrelvir and Ritonavir, for emergency use for COVID-19 (https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-first-oral-antiviral-treatment-covid-19). Nirmatrelvir is a SARS-CoV-2 main protease inhibitor that bears a nitrile group as ‘warhead’ [89], which demonstrate that active-site-directed compounds based on nitriles are still a good strategy as therapeutic cysteine proteases inhibitors. However, for CatK inhibitors, although nitrile is a good choice for the warhead, selectivity issues must be addressed in order to reduce the risk of off-target activity. Thus, the requirements for a minor side effect-prone CatK inhibitor may be reached on modulation of warhead electrophilicity that controls the reactivity and modifications in P2 and P3. Therefore, we expect that novel cysteine protease inhibitors will enter the clinical trials in the foreseeable future due to the successful development of chemicals coupling favorable pharmacodynamic and pharmacokinetic properties.
Protective effect of hypoxia inducible factor-1α gene therapy using recombinant adenovirus in cerebral ischaemia-reperfusion injuries in rats
Published in Pharmaceutical Biology, 2020
Ya-Qi Li, Zhi-Rong Hui, Tao Tao, Kang-Yu Shao, Zhi Liu, Min Li, Li-Ling Gu
CIR injury can induce apoptosis of ischaemic penumbra neurons (Cheng et al. 2014). The change in gene expression is the most prominent feature of CIR, which affects the expression of many proteins (Rao et al. 2002). The pathological process of apoptosis after ischaemia-reperfusion is extremely complex, involving a series of cascade reactions, calcium overload, excitatory amino acid toxicity, free radical production, protease activation, and inflammatory reaction (Jiang et al. 2017). The final stage involves the activation of caspase, a cysteine protease. In our study, at the different time points post-reperfusion, the expression of caspase-3 in the AdHIF-1α group was lower than that in the CIR and Ad groups. This was in accordance with the findings of previous studies (Aboutaleb et al. 2015; Yaidikar and Thakur 2015) that suggested that attenuation of CIR injury is associated with inhibition of the activation of caspase-3 (Yaidikar and Thakur 2015).