Direct detection of human adenovirus or SARS-CoV-2 with ability to inform infectivity using DNA aptamer-nanopore sensors.
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ABSTRACT:
SUBMITTER: Peinetti AS
PROVIDER: S-EPMC8457657 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity is a major concern in coronavirus disease 2019 (COVID-19) prevention and economic reopening. However, rigorous determination of SARS-CoV-2 infectivity is very difficult owing to its continuous evolution with over 10,000 single nucleotide polymorphisms (SNP) variants in many subtypes. We employ an algebraic topology-based machine learning model to quantitatively evaluate the binding free energy changes of SARS-CoV-2 spike glycoprotein (S protein) and host angiotensin-converting enzyme 2 receptor following mutations. We reveal that the SARS-CoV-2 virus becomes more infectious. Three out of six SARS-CoV-2 subtypes have become slightly more infectious, while the other three subtypes have significantly strengthened their infectivity. We also find that SARS-CoV-2 is slightly more infectious than SARS-CoV according to computed S protein-angiotensin-converting enzyme 2 binding free energy changes. Based on a systematic evaluation of all possible 3686 future mutations on the S protein receptor-binding domain, we show that most likely future mutations will make SARS-CoV-2 more infectious. Combining sequence alignment, probability analysis, and binding free energy calculation, we predict that a few residues on the receptor-binding motif, i.e., 452, 489, 500, 501, and 505, have high chances to mutate into significantly more infectious COVID-19 strains.
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Project description:We report cellular nanosponges as an effective medical countermeasure to the SARS-CoV-2 virus. Two types of cellular nanosponges are made of the plasma membranes derived from human lung epithelial type II cells or human macrophages. These nanosponges display the same protein receptors, both identified and unidentified, required by SARS-CoV-2 for cellular entry. It is shown that, following incubation with the nanosponges, SARS-CoV-2 is neutralized and unable to infect cells. Crucially, the nanosponge platform is agnostic to viral mutations and potentially viral species, as well. As long as the target of the virus remains the identified host cell, the nanosponges will be able to neutralize the virus.
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Project description:Endogenous glucocorticoids and their synthetic analogues, such as dexamethasone, stimulate receptor-mediated signal transduction mechanisms on target cells. Some of these mechanisms result in beneficial outcomes whereas others are deleterious in the settings of pathogen infections and immunological disorders. Here, we review recent studies by several groups, including our group, showing that glucocorticoids can directly interact with protein components on SARS-CoV-2, the causative agent of COVID-19. We postulate an antiviral defence mechanism by which endogenous glucocorticoids (e.g., cortisol produced in response to SARS-CoV-2 infection) can bind to multiple sites on SARS-CoV-2 surface protein, Spike, inducing conformational alterations in Spike subunit 1 (S1) that inhibit SARS-CoV-2 interaction with the host SARS-CoV-2 receptor, ACE2. We suggest that glucocorticoids-mediated inhibition of S1 interaction with ACE2 may, consequently, affect SARS-CoV-2 infectivity. Further, glucocorticoids interactions with Spike could protect against a broad spectrum of coronaviruses and their variants that utilize Spike for infection of the host. These notions may be useful for the design of new antivirals for coronavirus diseases.
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Project description:Based on a broad public database compilation, we support the hypothesis that germinal polymorphisms may regulate the expression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular target itself and proteases controlling the process of its shedding or, conversely, its internalization. Consequently, a genetic influence on individual susceptibility to coronavirus disease 2019 (COVID-19) infection is strongly suspected.
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Project description:Cardiovascular complications are major clinical hallmarks of acute and post-acute coronavirus disease 2019 (COVID-19). However, the mechanistic details of SARS-CoV-2 infectivity of endothelial cells remain largely unknown. Here, we demonstrate that the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein shares a similarity with the proline-rich binding ena/VASP homology (EVH1) domain and identified the endoplasmic reticulum (ER) resident calreticulin (CALR) as an S-RBD interacting protein. Our biochemical analysis showed that CALR, via its proline-rich (P) domain, interacts with S-RBD and modulates proteostasis of the S protein. Treatment of cells with the proteasomal inhibitor bortezomib increased the expression of the S protein independent of CALR, whereas the lysosomal/autophagy inhibitor bafilomycin 1A, which interferes with the acidification of lysosome, selectively augmented the S protein levels in a CALR-dependent manner. More importantly, the shRNA-mediated knockdown of CALR increased SARS-CoV-2 infection and impaired calcium homeostasis of human endothelial cells. This study provides new insight into the infectivity of SARS-CoV-2, calcium hemostasis, and the role of CALR in the ER-lysosome-dependent proteolysis of the spike protein, which could be associated with cardiovascular complications in COVID-19 patients.
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Project description: Not available
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Project description:OBJECTIVES:To summarise the evidence on the detection pattern and viral load of SARS-CoV-2 over the course of an infection (including any asymptomatic or pre-symptomatic phase), and the duration of infectivity. METHODS:A systematic literature search was undertaken in PubMed, Europe PubMed Central and EMBASE from 30 December 2019 to 12 May 2020. RESULTS:We identified 113 studies conducted in 17 countries. The evidence from upper respiratory tract samples suggests that the viral load of SARS-CoV-2 peaks around symptom onset or a few days thereafter, and becomes undetectable about two weeks after symptom onset; however, viral loads from sputum samples may be higher, peak later and persist for longer. There is evidence of prolonged virus detection in stool samples, with unclear clinical significance. No study was found that definitively measured the duration of infectivity; however, patients may not be infectious for the entire duration of virus detection, as the presence of viral ribonucleic acid may not represent transmissible live virus. CONCLUSION:There is a relatively consistent trajectory of SARS-CoV-2 viral load over the course of COVID-19 from respiratory tract samples, however the duration of infectivity remains uncertain.
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