scholarly journals Inhalable nanocatchers for SARS-CoV-2 inhibition

2021 ◽  
Vol 118 (29) ◽  
pp. e2102957118
Author(s):  
Han Zhang ◽  
Wenjun Zhu ◽  
Qiutong Jin ◽  
Feng Pan ◽  
Jiafei Zhu ◽  
...  

The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome (SARS)–like coronavirus (SARS-CoV-2), presents an urgent health crisis. More recently, an increasing number of mutated strains of SARS-CoV-2 have been identified globally. Such mutations, especially those on the spike glycoprotein to render its higher binding affinity to human angiotensin-converting enzyme II (hACE2) receptors, not only resulted in higher transmission of SARS-CoV-2 but also raised serious concerns regarding the efficacies of vaccines against mutated viruses. Since ACE2 is the virus-binding protein on human cells regardless of viral mutations, we design hACE2-containing nanocatchers (NCs) as the competitor with host cells for virus binding to protect cells from SARS-CoV-2 infection. The hACE2-containing NCs, derived from the cellular membrane of genetically engineered cells stably expressing hACE2, exhibited excellent neutralization ability against pseudoviruses of both wild-type SARS-CoV-2 and the D614G variant. To prevent SARS-CoV-2 infections in the lung, the most vulnerable organ for COVID-19, we develop an inhalable formulation by mixing hACE2-containing NCs with mucoadhesive excipient hyaluronic acid, the latter of which could significantly prolong the retention of NCs in the lung after inhalation. Excitingly, inhalation of our formulation could lead to potent pseudovirus inhibition ability in hACE2-expressing mouse model, without imposing any appreciable side effects. Importantly, our inhalable hACE2-containing NCs in the lyophilized formulation would allow long-term storage, facilitating their future clinical use. Thus, this work may provide an alternative tactic to inhibit SARS-CoV-2 infections even with different mutations, exhibiting great potential for treatment of the ongoing COVID-19 epidemic.

2020 ◽  
Vol 117 (44) ◽  
pp. 27141-27147 ◽  
Author(s):  
Lang Rao ◽  
Shuai Xia ◽  
Wei Xu ◽  
Rui Tian ◽  
Guocan Yu ◽  
...  

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the urgent need to rapidly develop therapeutic strategies for such emerging viruses without effective vaccines or drugs. Here, we report a decoy nanoparticle against COVID-19 through a powerful two-step neutralization approach: virus neutralization in the first step followed by cytokine neutralization in the second step. The nanodecoy, made by fusing cellular membrane nanovesicles derived from human monocytes and genetically engineered cells stably expressing angiotensin converting enzyme II (ACE2) receptors, possesses an antigenic exterior the same as source cells. By competing with host cells for virus binding, these nanodecoys effectively protect host cells from the infection of pseudoviruses and authentic SARS-CoV-2. Moreover, relying on abundant cytokine receptors on the surface, the nanodecoys efficiently bind and neutralize inflammatory cytokines including interleukin 6 (IL-6) and granulocyte−macrophage colony-stimulating factor (GM-CSF), and significantly suppress immune disorder and lung injury in an acute pneumonia mouse model. Our work presents a simple, safe, and robust antiviral nanotechnology for ongoing COVID-19 and future potential epidemics.


PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e6079 ◽  
Author(s):  
Pauline Kiatmetha ◽  
Charoonroj Chotwiwatthanakun ◽  
Pitchanee Jariyapong ◽  
Wanida Santimanawong ◽  
Puey Ounjai ◽  
...  

Background A virus-like particle (VLP) is an excellent tool for a compound delivery system due to its simple composition, symmetrical structure and self-assembly. Its surface modification both chemically and genetically is established, leading to the target-specific delivery and improved encapsulation efficiency. However, its physical stabilities against many harsh conditions that guarantee long term storage and oral administration have been much less studied. Methods IHHNV-VLPs were reconstructed from recombinant IHHNV capsid protein in E. coli. Their physical properties against three strong physical conditions including long term storage (0–30 days) in 4 °C, physical stabilities against broad ranged pH (4–9) and against three types of digestive enzymes were tested. Disassembly and reassembly of VLPs for encapsidating an enhanced green fluorescent protein tagged plasmid DNA (EGFP-VLPs) were controlled by the use of reducing agent (DTT) and calcium specific chelating agent (EGTA). Lastly, delivering ability of EGFP-VLPs was performed in vivo by intramuscular injection and traced the expression of GFP in the shrimp tissues 24 hr post-injection. Results Upon its purification, IHHNV-VLPs were able to be kept at 4 °C up to 30 days with only slight degradation. They were very stable in basic condition (pH 8–9) and to a lesser extent in acidic condition (pH 4–6) while they could stand digestions of trypsin and chymotrypsin better than pepsin. As similar with many other non-enveloped viruses, the assembly of IHHNV-VLPs was dependent on both disulfide bridging and calcium ions which allowed us to control disassembly and reassembly of these VLPs to pack EGFP plasmid DNA. IHHNV-VLPs could deliver EGFP plasmids into shrimp muscles and gills as evident by RT-PCR and confocal microscopy demonstrating the expression of GFP in the targeted tissues. Discussion There are extensive data in which capsid proteins of the non-enveloped viruses in the form of VLPs are constructed and used as nano-containers for therapeutic compound delivery. However, the bottleneck of its application as an excellent delivery container for oral administration would rely solely on physical stability and interacting ability of VLPs to the host cells. These properties are retained for IHHNV-VLPs reported herein. Thus, IHHNV-VLPs would stand as a good applicable nanocontainer to carry therapeutic agents towards the targeting tissues against ionic and digestive conditions via oral administration in aquaculture field.


2001 ◽  
Vol 6 (2) ◽  
pp. 3-14 ◽  
Author(s):  
R. Baronas ◽  
F. Ivanauskas ◽  
I. Juodeikienė ◽  
A. Kajalavičius

A model of moisture movement in wood is presented in this paper in a two-dimensional-in-space formulation. The finite-difference technique has been used in order to obtain the solution of the problem. The model was applied to predict the moisture content in sawn boards from pine during long term storage under outdoor climatic conditions. The satisfactory agreement between the numerical solution and experimental data was obtained.


Diabetes ◽  
1997 ◽  
Vol 46 (3) ◽  
pp. 519-523 ◽  
Author(s):  
G. M. Beattie ◽  
J. H. Crowe ◽  
A. D. Lopez ◽  
V. Cirulli ◽  
C. Ricordi ◽  
...  

2020 ◽  
Vol 59 (SL) ◽  
pp. SLLC01 ◽  
Author(s):  
Tomoki Murota ◽  
Toshiki Mimura ◽  
Ploybussara Gomasang ◽  
Shinji Yokogawa ◽  
Kazuyoshi Ueno

Author(s):  
O. Semenenko ◽  
O. Vodchyts ◽  
V. Koverga ◽  
R. Lukash ◽  
O. Lutsenko

The introduction and active use of information transmission and storage systems in the Ministry of Defense (MoD) of Ukraine form the need to develop ways of guaranteed removal of data from media after their use or long-term storage. Such a task is an essential component of the functioning of any information security system. The article analyzes the problems of guaranteed destruction of information on magnetic media. An overview of approaches to the guaranteed destruction of information on magnetic media of different types is presented, and partial estimates of the effectiveness of their application are given by some generally accepted indicators of performance evaluation. The article also describes the classification of methods of destruction of information depending on the influence on its medium. The results of the analysis revealed the main problems of application of software methods and methods of demagnetization of the information carrier. The issue of guaranteed destruction of information from modern SSD devices, which are actively used in the formation of new systems of information accumulation and processing, became particularly relevant in the article. In today's conditions of development of the Armed Forces of Ukraine, methods of mechanical and thermal destruction are more commonly used today. In the medium term, the vector of the use of information elimination methods will change towards the methods of physical impact by the pulsed magnetic field and the software methods that allow to store the information storage device, but this today requires specialists to develop new ways of protecting information in order to avoid its leakage.


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