Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 12 de 12
Filter
1.
Sens Actuators B Chem ; 357: 131415, 2022 Apr 15.
Article in English | MEDLINE | ID: covidwho-1720936

ABSTRACT

Facing the unstopped surges of COVID-19, an insufficient capacity of diagnostic testing jeopardizes the control of disease spread. Due to a centralized setting and a long turnaround, real-time reverse transcription polymerase chain reaction (real-time RT-PCR), the gold standard of viral detection, has fallen short in timely reflecting the epidemic status quo during an urgent outbreak. As such, a rapid screening tool is necessitated to help contain the spread of COVID-19 amid the countries where the vaccine implementations have not been widely deployed. In this work, we propose a saliva-based COVID-19 antigen test using the electrical double layer (EDL)-gated field-effect transistor-based biosensor (BioFET). The detection of SARS-CoV-2 nucleocapsid (N) protein is validated with limits of detection (LoDs) of 0.34 ng/mL (7.44 pM) and 0.14 ng/mL (2.96 pM) in 1× PBS and artificial saliva, respectively. The specificity is inspected with types of antigens, exhibiting low cross-reactivity among MERS-CoV, Influenza A virus, and Influenza B virus. This portable system is embedded with Bluetooth communication and user-friendly interfaces that are fully compatible with digital health, feasibly leading to an on-site turnaround, an effective management, and a proactive response taken by medical providers and frontline health workers.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312449

ABSTRACT

Machine learning has shown potential for optimizing existing molecules with more desirable properties, a critical step towards accelerating new chemical discovery. In this work, we propose QMO, a generic query-based molecule optimization framework that exploits latent embeddings from a molecule autoencoder. QMO improves the desired properties of an input molecule based on efficient queries, guided by a set of molecular property predictions and evaluation metrics. We show that QMO outperforms existing methods in the benchmark tasks of optimizing molecules for drug likeliness and solubility under similarity constraints. We also demonstrate significant property improvement using QMO on two new and challenging tasks that are also important in real-world discovery problems: (i) optimizing existing SARS-CoV-2 Main Protease inhibitors toward higher binding affinity;and (ii) improving known antimicrobial peptides towards lower toxicity. Results from QMO show high consistency with external validations, suggesting effective means of facilitating molecule optimization problems with design constraints.

3.
Cell Metab ; 34(3): 424-440.e7, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1676683

ABSTRACT

Coronavirus disease 2019 (COVID-19) represents a systemic disease that may cause severe metabolic complications in multiple tissues including liver, kidney, and cardiovascular system. However, the underlying mechanisms and optimal treatment remain elusive. Our study shows that impairment of ACE2 pathway is a key factor linking virus infection to its secondary metabolic sequelae. By using structure-based high-throughput virtual screening and connectivity map database, followed with experimental validations, we identify imatinib, methazolamide, and harpagoside as direct enzymatic activators of ACE2. Imatinib and methazolamide remarkably improve metabolic perturbations in vivo in an ACE2-dependent manner under the insulin-resistant state and SARS-CoV-2-infected state. Moreover, viral entry is directly inhibited by these three compounds due to allosteric inhibition of ACE2 binding to spike protein on SARS-CoV-2. Taken together, our study shows that enzymatic activation of ACE2 via imatinib, methazolamide, or harpagoside may be a conceptually new strategy to treat metabolic sequelae of COVID-19.


Subject(s)
COVID-19/drug therapy , Imatinib Mesylate/therapeutic use , Metabolic Diseases/drug therapy , Methazolamide/therapeutic use , SARS-CoV-2/drug effects , Angiotensin-Converting Enzyme 2/drug effects , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/complications , COVID-19/metabolism , COVID-19/virology , Cells, Cultured , Chlorocebus aethiops , Down-Regulation/drug effects , HEK293 Cells , Human Umbilical Vein Endothelial Cells , Humans , Imatinib Mesylate/pharmacology , Male , Metabolic Diseases/metabolism , Metabolic Diseases/virology , Methazolamide/pharmacology , Mice , Mice, Inbred C57BL , Mice, Obese , Mice, Transgenic , SARS-CoV-2/physiology , Vero Cells , Virus Internalization/drug effects
4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-291750

ABSTRACT

Machine learning based methods have shown potential for optimizing existing molecules with more desirable properties, a critical step towards accelerating new chemical discovery. Here we propose QMO, a generic query-based molecule optimization framework that exploits latent embeddings from a molecule autoencoder. QMO improves the desired properties of an input molecule based on efficient queries, guided by a set of molecular property predictions and evaluation metrics. We show that QMO outperforms existing methods in the benchmark tasks of optimizing small organic molecules for drug-likeness and solubility under similarity constraints. We also demonstrate significant property improvement using QMO on two new and challenging tasks that are also important in real-world discovery problems: (i) optimizing existing potential SARS-CoV-2 Main Protease inhibitors toward higher binding affinity;and (ii) improving known antimicrobial peptides towards lower toxicity. Results from QMO show high consistency with external validations, suggesting effective means to facilitate material optimization problems with design constraints.

5.
Advanced Materials Technologies ; n/a(n/a):2100842, 2021.
Article in English | Wiley | ID: covidwho-1408260

ABSTRACT

Abstract In light of the swift outspread and considerable mortality, coronavirus disease 2019 (COVID-19) necessitates a rapid screening tool and a precise diagnosis. Saliva is considered as an alternative specimen to detect the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since the viral load is comparable to what are found in a throat and a nasal cavity. The electrical double layer (EDL)-gated field-effect transistor-based biosensor (BioFET) emerges as a promising candidate for salivary COVID-19 tests due to a high sensitivity, a portable configuration, a label-free operation, and a matrix insensitivity. In this work, the authors utilize EDL-gated BioFETs to detect complementary DNAs (cDNAs) and viral RNAs with various testing conditions such as switches of probes, temperature treatments, and matrices. The selectivity is confirmed with cDNA and noncomplementary DNA (ncDNA), exhibiting an eightfold difference in electrical signals. The matrix insensitivity is evaluated, and BioFETs successfully validate the detection of SARS-CoV-2 N-gene RNA down to 1 fm in diluted human saliva with a 95°C- and a 25°C-treatment, respectively. This proposed system has a high potential to be deployed for an on-site COVID-19 screening, improving the disease control and benefitting frontline healthcare system.

6.
Adv Mater Technol ; 7(1): 2100842, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1404534

ABSTRACT

In light of the swift outspread and considerable mortality, coronavirus disease 2019 (COVID-19) necessitates a rapid screening tool and a precise diagnosis. Saliva is considered as an alternative specimen to detect the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since the viral load is comparable to what are found in a throat and a nasal cavity. The electrical double layer (EDL)-gated field-effect transistor-based biosensor (BioFET) emerges as a promising candidate for salivary COVID-19 tests due to a high sensitivity, a portable configuration, a label-free operation, and a matrix insensitivity. In this work, the authors utilize EDL-gated BioFETs to detect complementary DNAs (cDNAs) and viral RNAs with various testing conditions such as switches of probes, temperature treatments, and matrices. The selectivity is confirmed with cDNA and noncomplementary DNA (ncDNA), exhibiting an eightfold difference in electrical signals. The matrix insensitivity is evaluated, and BioFETs successfully validate the detection of SARS-CoV-2 N-gene RNA down to 1 fm in diluted human saliva with a 95°C- and a 25°C-treatment, respectively. This proposed system has a high potential to be deployed for an on-site COVID-19 screening, improving the disease control and benefitting frontline healthcare system.

7.
Nat Commun ; 12(1): 2790, 2021 05 13.
Article in English | MEDLINE | ID: covidwho-1387341

ABSTRACT

SARS-CoV-2 is of zoonotic origin and contains a PRRA polybasic cleavage motif which is considered critical for efficient infection and transmission in humans. We previously reported on a panel of attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction of the spike protein. Here, we characterize pathogenicity, immunogenicity, and protective ability of a further cell-adapted SARS-CoV-2 variant, Ca-DelMut, in in vitro and in vivo systems. Ca-DelMut replicates more efficiently than wild type or parental virus in Vero E6 cells, but causes no apparent disease in hamsters, despite replicating in respiratory tissues. Unlike wild type virus, Ca-DelMut causes no obvious pathological changes and does not induce elevation of proinflammatory cytokines, but still triggers a strong neutralizing antibody and T cell response in hamsters and mice. Ca-DelMut immunized hamsters challenged with wild type SARS-CoV-2 are fully protected, with little sign of virus replication in the upper or lower respiratory tract, demonstrating sterilizing immunity.


Subject(s)
COVID-19/diagnosis , Mutation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Virus Replication/genetics , Animals , COVID-19/immunology , COVID-19/virology , Cell Line, Tumor , Chlorocebus aethiops , Cricetinae , Cytokines/immunology , Cytokines/metabolism , Female , Host-Pathogen Interactions , Humans , Male , Mesocricetus , Mice, Inbred BALB C , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Vero Cells , Virulence/genetics , Virulence/immunology
8.
Cancer Manag Res ; 13: 5899-5906, 2021.
Article in English | MEDLINE | ID: covidwho-1344195

ABSTRACT

PURPOSE: To assess whether the COVID-19 pandemic delayed breast cancer diagnosis in Taiwan, an Asian country with a low COVID-19 incidence. METHODS: The monthly volume of breast biopsies and breast cancers during the COVID-19 pandemic (during January 21 and July 31, 2020) was compared to the same period in 2019 (pre-COVID-19). RESULTS: Taiwan recorded a lower COVID-19 incidence rate (20.2 cases per million population) than other Asian countries. The screen-detected lesions accounted for 55% and 36% of 2019 and 2020 total biopsied lesions, respectively. Total breast biopsy, mammography-guided, and ultrasound-guided biopsies decreased by 17%, 23%, and 14%, respectively, from pre-COVID-19 to COVID-19. Monthly differences were significant in total biopsy (p=0.03), mammography-guided biopsy (p=0.04), and a benign pathology result after breast biopsy (p<0.01). Nearly 46% decline was noted in the biopsy results of non-invasive breast cancer in 2020. The number of total breast cancers and early breast cancers (stages 0 and 1) decreased by 10% and 38%, respectively, during pandemic. Individuals with early breast cancer accounted for 71% and 49% of the total diagnosed breast cancer in the pre-COVID-19 and COVID-19 periods, respectively (p<0.001). CONCLUSION: The pandemic significantly delayed early breast cancer detection in Taiwan despite low COVID-19 incidence. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04750018.

9.
ClinicalTrials.gov; 06/02/2021; TrialID: NCT04750018
Clinical Trial Register | ICTRP | ID: ictrp-NCT04750018

ABSTRACT

Condition:

COVID-19;Breast Cancer

Intervention:

Other: surgery

Primary outcome:

breast cancer

Criteria:


Inclusion Criteria:

- Receiving breast exam 2019-2020

Exclusion Criteria:

- lost clinical follow-up


10.
SciFinder; 2020.
Preprint | SciFinder | ID: ppcovidwho-5160

ABSTRACT

A review. At Dec. 2019, a new coronavirus (SARS-CoV-2) broke out in China and spread rapidly to many other countries, threating global public health security. To satisfy the urgent demand of SARS-CoV-2 detection, many enterprises and research institutions have developed a number of detection methods and products. The research progress on detection methods of SARS-CoV-2 are reviewed in this paper. The principle of these detection techniques is introduced, and their advantages and limitations, as well as some typical research works discusses are illustrated.

12.
Emerg Microbes Infect ; 9(1): 837-842, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-72297

ABSTRACT

The emergence of SARS-CoV-2 has led to the current global coronavirus pandemic and more than one million infections since December 2019. The exact origin of SARS-CoV-2 remains elusive, but the presence of a distinct motif in the S1/S2 junction region suggests the possible acquisition of cleavage site(s) in the spike protein that promoted cross-species transmission. Through plaque purification of Vero-E6 cultured SARS-CoV-2, we found a series of variants which contain 15-30-bp deletions (Del-mut) or point mutations respectively at the S1/S2 junction. Examination of the original clinical specimen from which the isolate was derived, and 26 additional SARS-CoV-2 positive clinical specimens, failed to detect these variants. Infection of hamsters shows that one of the variants (Del-mut-1) which carries deletion of 10 amino acids (30bp) does not cause the body weight loss or more severe pathological changes in the lungs that is associated with wild type virus infection. We suggest that the unique cleavage motif promoting SARS-CoV-2 infection in humans may be under strong selective pressure, given that replication in permissive Vero-E6 cells leads to the loss of this adaptive function. It would be important to screen the prevalence of these variants in asymptomatic infected cases. The potential of the Del-mut variants as an attenuated vaccine or laboratory tool should be evaluated.


Subject(s)
Coronavirus Infections/pathology , Disease Models, Animal , Mesocricetus , Pneumonia, Viral/pathology , SARS Virus/genetics , SARS Virus/pathogenicity , Sequence Deletion , Spike Glycoprotein, Coronavirus/genetics , Amino Acid Sequence , Animals , Base Sequence , COVID-19 , Cell Line , Chlorocebus aethiops , Coronavirus Infections/virology , Female , Host Specificity , Humans , Lung/pathology , Male , Pandemics , Pneumonia, Viral/virology , SARS Virus/growth & development , SARS Virus/isolation & purification , Spike Glycoprotein, Coronavirus/chemistry , Vero Cells , Virulence
SELECTION OF CITATIONS
SEARCH DETAIL