scholarly journals Hydrodynamics of spike proteins dictate a transport-affinity competition for SARS-CoV-2 and other enveloped viruses

2022 ◽  
Author(s):  
Nicolas Moreno ◽  
Daniela Moreno-Chaparro ◽  
Florencio Balboa Usabiaga ◽  
Marco Ellero

Many viruses, such as SARS-CoV-2 or Influenza, possess spike-decorated envelopes. Depending on the virus type, a large variability is present in spikes number, morphology and reactivity, which remains generally unexplained. Since viruses' transmissibility depend on features beyond their genetic sequence, new tools are required to discern the effects of spikes functionality, interaction, and morphology. Here, we postulate the relevance of hydrodynamic interactions in the viral infectivity of enveloped viruses and propose micro-rheological characterization as a platform for viruses differentiation. To understand how the spikes affect virion mobility and infectivity, we investigate the diffusivity of spike-decorate structures using mesoscopic-hydrodynamic simulations. Furthermore, we explored the interplay between affinity and passive viral transport. Our results revealed that the diffusional mechanism of SARS-CoV-2 is strongly influenced by the size and distribution of its spikes. We propose and validate a universal mechanism to explain the link between optimal virion structure and maximal infectivity for many virus families.

2010 ◽  
Vol 84 (10) ◽  
pp. 4889-4897 ◽  
Author(s):  
Juha T. Huiskonen ◽  
Jussi Hepojoki ◽  
Pasi Laurinmäki ◽  
Antti Vaheri ◽  
Hilkka Lankinen ◽  
...  

ABSTRACT Hantaviruses (family Bunyaviridae) are rodent-borne emerging viruses that cause a serious, worldwide threat to human health. Hantavirus diseases include hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome. Virions are enveloped and contain a tripartite single-stranded negative-sense RNA genome. Two types of glycoproteins, GN and GC, are embedded in the viral membrane and form protrusions, or “spikes.” The membrane encloses a ribonucleoprotein core, which consists of the RNA segments, the nucleocapsid protein, and the RNA-dependent RNA polymerase. Detailed information on hantavirus virion structure and glycoprotein spike composition is scarce. Here, we have studied the structures of Tula hantavirus virions using electron cryomicroscopy and tomography. Three-dimensional density maps show how the hantavirus surface glycoproteins, membrane, and ribonucleoprotein are organized. The structure of the GN-GC spike complex was solved to 3.6-nm resolution by averaging tomographic subvolumes. Each spike complex is a square-shaped assembly with 4-fold symmetry. Spike complexes formed ordered patches on the viral membrane by means of specific lateral interactions. These interactions may be sufficient for creating membrane curvature during virus budding. In conclusion, the structure and assembly principles of Tula hantavirus exemplify a unique assembly paradigm for enveloped viruses.


1996 ◽  
Vol 10 (23n24) ◽  
pp. 3211-3217 ◽  
Author(s):  
J.R. MELROSE ◽  
S. ITOH ◽  
R.C. BALL

We report preliminary results for 3D simulations of a reduced model of electrorheological (ER) fluids. The hydrodynamic interactions are just squeeze flow lubrication and the electrostatic interactions that of point dipoles. In the low Mason number regime the same layer structure seen in earlier non-hydrodynamic simulations is found.


1999 ◽  
Vol 73 (8) ◽  
pp. 6370-6379 ◽  
Author(s):  
Alexandra Trkola ◽  
Cynthia Gordon ◽  
Jamie Matthews ◽  
Elizabeth Maxwell ◽  
Tom Ketas ◽  
...  

ABSTRACT We have studied the mechanisms by which the CC-chemokine RANTES can enhance the infectivities of human immunodeficiency virus type 1 (HIV-1) and other enveloped viruses, when present at concentrations in excess of 500 ng/ml in vitro. Understanding the underlying mechanisms might throw light on fundamental processes of viral infection, in particular for HIV-1. Our principal findings are twofold: firstly, that oligomers of RANTES can cross-link enveloped viruses, including HIV-1, to cells via glycosaminoglycans (GAGs) present on the membranes of both virions and cells; secondly, that oligomers of RANTES interact with cell-surface GAGs to transduce a herbimycin A-sensitive signal which, over a period of several hours, renders the cells more permissive to infection by several viruses, including HIV-1. The enhancement mechanisms require that RANTES oligomerize either in solution or following binding to GAGs, since no viral infectivity enhancement is observed with a mutant form of the RANTES molecule that contains a single-amino-acid change (glutamic acid to serine at position 66) which abrogates oligomerization.


Author(s):  
K. Rekrut ◽  
K. Schleuter

Confirmation of herpes simplex virus (HSV) from genital lesions of obstetrical (OB) patients may affect both the management of the delivery and of the neonate.(l,2) During 1992 and 1993, 4,450 genital specimens from OB patients were submitted in viral transport media for herpes culture. The specimens were inoculated into MRC-5, Vero, and A-549 tissue culture tubes, incubated, and examined daily for 7 days for cytopathic effect (CPE). The original specimens were frozen at −70° C until final reports were issued. Culture tubes with CPE were tested by the Dupont Herpchek enzyme immuno assay (EIA) to confirm the presence of herpes simplex virus (HSV). (3,4) 170 OB patient specimens were positive by culture and confirmed by EIA.There were also 63 cultures exhibiting CPE ressembling HSV which were negative by EIA testing, which failed to pass in fresh tissue culture cells or progress to more enhanced CPE in culture. These original specimens were screened by electron microscopy after direct ultracentrifugation employing the Beckman airfuge with the EM 90 rotor on to formvar carbon-coated 300 mesh copper grids and negatively stained with 2% PTA.


1992 ◽  
Vol 67 (01) ◽  
pp. 019-027 ◽  
Author(s):  
Joseph E Addiego ◽  
Edward Gomperts ◽  
Liu Shu-Len ◽  
Patricia Bailey ◽  
Suzanne G Courter ◽  
...  

SummaryTo reduce the risk of pathogenic virus transmission associated with the therapeutic administration of plasma-derived antihemophilic factor (FVIIIc), a process utilizing anti-FVIIIc immunoaffinity chromatography to isolate FVIIIc has been developed. In addition, the starting cryoprecipitate solution has been treated with an organic solvent/detergent mixture to inactivate lipid-enveloped viruses. A final ion exchange chromatography step is used to further remove contaminants, e.g., anti-FVIIIc antibody, potentially leached with FVIIIc during the immunoaffinity step. The purified FVTII is stabilized for lyophili-zation and storage by the addition of human albumin. The monoclonal anti-FVIIIc antibody used in the immunoaffinity step of the process is not detectable in the final preparation. Viral reduction studies performed at specific steps of the process demonstrate that 11 logs of human immunodeficiency virus (HIV) and greater than 4-5 logs of other lipid-enveloped viruses are inactivated within the first 30 s of exposure to the solvent/ detergent mixture and 4-5 logs of various model viruses, e. g. Endomyocarditis virus (EMC), are physically removed during washing of the immunoaffinity column. The lyophilized product is reconstituted using sterile water in a matter of seconds.The pharmacokinetics of Hemofil® M were compared to those obtained using a standard heat-treated concentrate (Hemofil® CT) in five severe factor VIII deficient hemophiliacs in a randomized, cross-over study. No statistically significant differences were observed in mean half life (p >0.6) or median recovery (p = 0.4) between the two preparations. No clinically significant adverse effects were observed in patients receiving either FVIII preparation.In addition, 43 patients at 18 different centers underwent pharmacokinetic studies, with a nominal dose of 50 u/kg FVIIIc Hemofil® M. The mean recovery was 103.6%, and the t 1/2 was 14.6 h. The recovery of FVIII in this group was as expected, providing an increase of assayed FVIII of approximately 2% per unit of FVTII/kg infused.Clinical trials using Hemofil® M have been initiated in 124 hemophilia A patients. The safety and efficacy of Hemofil® M has been established. To date, 0 of 60 patients tested have seroconverted to HIV. None of the previously untreated patients show clinical or laboratory evidence of Non-A, Non-B hepatitis (NANB), with 21 patients remaining negative as far as presence of antibodies to the Hepatitis C virus (a-HCV negative) at least 6 months after the initial infusion. There is no evidence of neoantigenicity, evidenced by seroconversion to murine antibody. An 8.7% (2 of 23) prevalence of anti-FVIIIc inhibitor development has been observed in previously untreated patients with FVIIIc⩽3%, receiving only the monoclonally purified solvent/ detergent treated FVIII concentrate while on study and on poststudy surveillance. All patients demonstrated clinical hemostasis following product use for either on demand bleeding or surgical prophylaxis.


1995 ◽  
Vol 74 (03) ◽  
pp. 868-873 ◽  
Author(s):  
Silvana Arrighi ◽  
Roberta Rossi ◽  
Maria Giuseppina Borri ◽  
Vladimir Lesnikov ◽  
Marina Lesnikov ◽  
...  

SummaryTo improve the safety of plasma derived factor VIII (FVIII) concentrate, we introduced a final super heat treatment (100° C for 30 min) as additional virus inactivation step applied to a lyophilized, highly purified FVIII concentrate (100 IU/mg of proteins) already virus inactivated using the solvent/detergent (SID) method during the manufacturing process.The efficiency of the super heat treatment was demonstrated in inactivating two non-lipid enveloped viruses (Hepatitis A virus and Poliovirus 1). The loss of FVIII procoagulant activity during the super heat treatment was of about 15%, estimated both by clotting and chromogenic assays. No substantial changes were observed in physical, biochemical and immunological characteristics of the heat treated FVIII concentrate in comparison with those of the FVIII before heat treatment.


Author(s):  
Trevor Simcox ◽  
Lauren Seo ◽  
Kevin Dunham ◽  
Shengnan Huang ◽  
Catherine Petchprapa ◽  
...  

Abstract Background The etiology of carpal tunnel syndrome (CTS) is multifactorial. Static mechanical characteristics of CTS have been described, but dynamic (muscular) parameters remain obscure. We believe that musculature overlying the transverse carpal ligament may have an effect on carpal tunnel pressure and may explain the prevalence of CTS in manual workers. Questions/Purposes To utilize magnetic resonance imaging (MRI) imaging to estimate the amount of muscle crossing the area of the carpal tunnel and to compare these MRI measurements in patients with and without documented CTS. Methods A case–control study of wrist MRI scans between January 1, 2018, and December 1, 2019, was performed. Patients with a diagnosis of CTS were matched by age and gender with controls without a diagnosis of CTS. Axial MRI cuts at the level of the hook of the hamate were used to measure the thenar and hypothenar muscle depth overlying the carpal tunnel. Muscle depth was quantified in millimeters at three points: midcapitate, capitate–hamate border, capitate–trapezoid border. Average depth was calculated by dividing the cross-sectional area (CSA) by the transverse carpal ligament width. Statistical analysis included Student's t-test, chi-square test, and Pearson's correlation coefficient calculation. Results A total of 21 cases and 21 controls met the inclusion criteria for the study. There were no significant differences in demographics between case and control groups. The location and depth of the musculature crossing the carpal tunnel were highly variable in all areas evaluated. A significantly positive correlation was found between proximal median nerve CSA and muscle depth in the capitate–hamate area (correlation coefficient = 0.375; p = 0.014). CSA was not significantly associated with chart documented CTS. Conclusions We found large variability in our measurements. This likely reflects true anatomical variation. The significance of our findings depends on the location of the muscles and the line of pull and their effect on the mechanics of the transverse carpal ligament. Future research will focus on refining measurement methodology and understanding the mechanical effect of the muscular structure and insertions on carpal tunnel pressure. Level of Evidence This is a Level 3, case–control study.


TAPPI Journal ◽  
2019 ◽  
Vol 18 (11) ◽  
pp. 641-649
Author(s):  
JOSHUA OMAMBALA ◽  
CARL MCINTYRE

The vast majority of tissue production uses creping to achieve the required set of properties on the base sheet. The Yankee coating helps to develop the desired crepe that in turn determines properties such as bulk and softness. The adhesion of the sheet to the Yankee surface is a very important characteristic to consider in achieving the desired crepe. The coating mix usually consists of the adhesive, modifier, and release. A good combination of these components is essential to achieving the desired properties of the tissue or towel, which often are determined by trials on the machine that can be time consuming and lead to costly rejects. In this paper, five compositions of an industrial Yankee coating adhesive, modifier, and release were examined rheologically. The weight ratio of the adhesive was kept constant at 30% in all five compositions and the modifier and release ratios were varied. The normal force and work done by the different compositions have been shown at various temperatures simulating that of the Yankee surface, and the oscillatory test was carried out to explain the linear and nonlinear viscoelastic characteristic of the optimal coating composition.


Author(s):  
S.M. Thomas ◽  
D. Bloomer ◽  
R.J. Martin ◽  
A. Horrocks

Applying water efficiently is increasingly important for dairy farmers and other users of surface and groundwater resources to maintain sustainable production. However, irrigation is rarely monitored. We used a questionnaire survey and measurements of five spray irrigation systems working in normal farm conditions to make observations on how efficiently irrigation is being managed. Survey results from 93 dairy farmers showed that, although the farmers believe they know how much water is being applied during irrigation, only 60% make measurements, and about 18% measure irrigation uniformity. Catch-can measurement of irrigation application depth for the different spray systems indicated large variability in application depths during irrigation, and field distribution uniformity ranged greatly between the different systems, decreasing in the order of centre pivots >travelling irrigators> K-line. Changes in irrigation system settings were sometimes made without considering application depths or uniformity. If our five case studies are typical, they may explain the large range of seasonal irrigation amounts recorded in the survey. We recommend that farmers monitor irrigation application depths and uniformity to help manage irrigation water efficiently and to help them estimate the value of irrigation to their enterprise. Keywords: distribution uniformity, water use efficiency, catch cans


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