Characterization, mechanism of anticoagulant action, and assessment of therapeutic potential of a fibrinolytic serine protease (Brevithrombolase) purified from Brevibacillus brevis strain FF02B

Biochimie ◽  
2014 ◽  
Vol 103 ◽  
pp. 50-60 ◽  
Author(s):  
Sourav Majumdar ◽  
Biplob Sarmah ◽  
Debananda Gogoi ◽  
Subhamoy Banerjee ◽  
Siddhartha S. Ghosh ◽  
...  
2001 ◽  
Vol 281 (1) ◽  
pp. L16-L23 ◽  
Author(s):  
Robert J. Bridges ◽  
Ben B. Newton ◽  
Joseph M. Pilewski ◽  
Daniel C. Devor ◽  
Christopher T. Poll ◽  
...  

To test the hypothesis that Na+ transport in human bronchial epithelial (HBE) cells is regulated by a protease-mediated mechanism, we investigated the effects of BAY 39-9437, a recombinant Kunitz-type serine protease inhibitor, on amiloride-sensitive short-circuit current of normal [non-cystic fibrosis (CF) cells] and CF HBE cells. Mucosal treatment of non-CF and CF HBE cells with BAY 39-9437 decreased the short-circuit current, with a half-life of ∼45 min. At 90 min, BAY 39-9437 (470 nM) reduced Na+ transport by ∼70%. The inhibitory effect of BAY 39-9437 was concentration dependent, with a half-maximal inhibitory concentration of ∼25 nM. Na+ transport was restored to control levels, with a half-life of ∼15 min, on washout of BAY 39-9437. In addition, trypsin (1 μM) rapidly reversed the inhibitory effect of BAY 39-9437. These data indicate that Na+transport in HBE cells is activated by a BAY 39-9437-inhibitable, endogenously expressed serine protease. BAY 39-9437 inhibition of this serine protease maybe of therapeutic potential for the treatment of Na+ hyperabsorption in CF.


2020 ◽  
Vol 3 (9) ◽  
pp. e202000786 ◽  
Author(s):  
Dorothea Bestle ◽  
Miriam Ruth Heindl ◽  
Hannah Limburg ◽  
Thuy Van Lam van ◽  
Oliver Pilgram ◽  
...  

The novel emerged SARS-CoV-2 has rapidly spread around the world causing acute infection of the respiratory tract (COVID-19) that can result in severe disease and lethality. For SARS-CoV-2 to enter cells, its surface glycoprotein spike (S) must be cleaved at two different sites by host cell proteases, which therefore represent potential drug targets. In the present study, we show that S can be cleaved by the proprotein convertase furin at the S1/S2 site and the transmembrane serine protease 2 (TMPRSS2) at the S2′ site. We demonstrate that TMPRSS2 is essential for activation of SARS-CoV-2 S in Calu-3 human airway epithelial cells through antisense-mediated knockdown of TMPRSS2 expression. Furthermore, SARS-CoV-2 replication was also strongly inhibited by the synthetic furin inhibitor MI-1851 in human airway cells. In contrast, inhibition of endosomal cathepsins by E64d did not affect virus replication. Combining various TMPRSS2 inhibitors with furin inhibitor MI-1851 produced more potent antiviral activity against SARS-CoV-2 than an equimolar amount of any single serine protease inhibitor. Therefore, this approach has considerable therapeutic potential for treatment of COVID-19.


Pathogens ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 307 ◽  
Author(s):  
Muhammad Shahid Nadeem ◽  
Mazin A. Zamzami ◽  
Hani Choudhry ◽  
Bibi Nazia Murtaza ◽  
Imran Kazmi ◽  
...  

The ongoing episode of coronavirus disease 19 (COVID-19) has imposed a serious threat to global health and the world economy. The disease has rapidly acquired a pandemic status affecting almost all populated areas of the planet. The causative agent of COVID-19 is a novel coronavirus known as SARS-CoV-2. The virus has an approximate 30 kb single-stranded positive-sense RNA genome, which is 74.5% to 99% identical to that of SARS-CoV, CoV-pangolin, and the coronavirus the from horseshoe bat. According to available information, SARS-CoV-2 is inferred to be a recombinant virus that originated from bats and was transmitted to humans, possibly using the pangolin as the intermediate host. The interaction of the SARS-CoV-2 spike protein with the human ACE2 (angiotensin-converting enzyme 2) receptor, and its subsequent cleavage by serine protease and fusion, are the main events in the pathophysiology. The serine protease inhibitors, spike protein-based vaccines, or ACE2 blockers may have therapeutic potential in the near future. At present, no vaccine is available against COVID-19. The disease is being treated with antiviral, antimalarial, anti-inflammatory, herbal medicines, and active plasma antibodies. In this context, the present review article provides a cumulative account of the recent information regarding the viral characteristics, potential therapeutic targets, treatment options, and prospective research questions.


1997 ◽  
Vol 22 (3) ◽  
pp. 285 ◽  
Author(s):  
Y. Nakayama ◽  
K. Senokuchi ◽  
H. Nakai ◽  
T. Obata ◽  
M. Kawamura

2020 ◽  
Vol 477 (2) ◽  
pp. 459-459
Author(s):  
Lalith K. Chaganti ◽  
Shubhankar Dutta ◽  
Raja Reddy Kuppili ◽  
Mriganka Mandal ◽  
Kakoli Bose

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