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1.
Science Advances ; 8(18):eabm6909, 2022.
Article in English | MEDLINE | ID: covidwho-1832318

ABSTRACT

Assembling nanobodies (Nbs) into polyvalent multimers is a powerful strategy for improving the effectiveness of Nb-based therapeutics and biotechnological tools. However, generally effective approaches to Nb assembly are currently restricted to the amino or carboxyl termini, greatly limiting the diversity of Nb multimer topologies that can be produced. Here, we show that reactive tetrazine groups-site-specifically inserted by genetic code expansion at Nb surface sites-are compatible with Nb folding and function, enabling Nb assembly at any desired point. Using two anti-SARS-CoV-2 Nbs with viral neutralization ability, we created Nb homo- and heterodimers with improved properties compared with conventionally linked Nb homodimers, which, in the case of our tetrazine-conjugated trimer, translated into enhanced viral neutralization. Thus, this tetrazine-based approach is a generally applicable strategy that greatly increases the accessible range of Nb assembly topologies, and thereby adds the optimization of topology as an effective avenue to generate Nb assemblies with improved efficacy.

2.
Journal of Allergy and Clinical Immunology ; 149(2):AB102-AB102, 2022.
Article in English | Web of Science | ID: covidwho-1798230
3.
Allergy: European Journal of Allergy and Clinical Immunology ; 76(SUPPL 110):194, 2021.
Article in English | EMBASE | ID: covidwho-1570350

ABSTRACT

Background: The CORAL study is a cross-sectional study of the impact of the Coronavirus pandemic on allergic and autoimmune dysregulation of infants born in March, April and May 2020, during Ireland's 1 st COVID-19 pandemic Lockdown. Method: Invitations were sent to families of 3065 term, singleton babies. Exclusion criteria were ante-natal PCR-proven SARSCoV-2 in a parent or co-dwelling person, IV antibiotics in neonatal period, multiple births and major congenital anomalies. At 6 months babies were invited to attend CHI Connolly for point-of-care SARSCoV-2 antibody testing. Results: Of the 3065 letters sent 353 babies were enrolled.53.7% of enrolled infants were male, 78.4% were white-Irish, average birth weight was 3.506kg. 45% were first-born and 95.5% of mothers were educated at 3 rd level or higher. Babies' average number of close contacts other than household members was 2.3 during lockdown and 5.6 afterwards. 42.5% were reported to be currently breast-fed at enrolment. By 6 months, 97% of infants had solid foods introduced but only 24.5% had tried egg and 9.6% had tried peanut. Complete primary immunisation uptake at 6 months was 99%. Lastly, 3 babies out of 200 (1.3%) tested showed presence of IgM & IgG SARSCoV-2 antibodies;2 were PCR negative, the other PCR positive. Conclusion: Initial breastfeeding and immunisation uptake to 6 months are reassuringly high in this self-selected, highly-educated cohort. The rare positive antibody tests suggest recent or current infection, so newborn babies appear to have been protected from SARSCoV-2 exposure during the 1 st COVID Pandemic lockdown.

5.
Nano Today ; 40: 101279, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1401730

ABSTRACT

Humans are exposed to nanoscopical nanobiovectors (e.g. coronavirus SARS-CoV-2) as well as abiotic metal/carbon-based nanomaterials that enter cells serendipitously or intentionally. Understanding the interactions of cell membranes with these abiotic and biotic nanostructures will facilitate scientists to design better functional nanomaterials for biomedical applications. Such knowledge will also provide important clues for the control of viral infections and the treatment of virus-induced infectious diseases. In the present review, the mechanisms of endocytosis are reviewed in the context of how nanomaterials are uptaken into cells. This is followed by a detailed discussion of the attributes of man-made nanomaterials (e.g. size, shape, surface functional groups and elasticity) that affect endocytosis, as well as the different human cell types that participate in the endocytosis of nanomaterials. Readers are then introduced to the concept of viruses as nature-derived nanoparticles. The mechanisms in which different classes of viruses interact with various cell types to gain entry into the human body are reviewed with examples published over the last five years. These basic tenets will enable the avid reader to design advanced drug delivery and gene transfer nanoplatforms that harness the knowledge acquired from endocytosis to improve their biomedical efficacy. The review winds up with a discussion on the hurdles to be addressed in mimicking the natural mechanisms of endocytosis in nanomaterials design.

6.
Int J Mol Sci ; 22(11)2021 May 21.
Article in English | MEDLINE | ID: covidwho-1244038

ABSTRACT

In late 2019, a new member of the Coronaviridae family, officially designated as "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2), emerged and spread rapidly. The Coronavirus Disease-19 (COVID-19) outbreak was accompanied by a high rate of morbidity and mortality worldwide and was declared a pandemic by the World Health Organization in March 2020. Within the Coronaviridae family, SARS-CoV-2 is considered to be the third most highly pathogenic virus that infects humans, following the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV). Four major mechanisms are thought to be involved in COVID-19 pathogenesis, including the activation of the renin-angiotensin system (RAS) signaling pathway, oxidative stress and cell death, cytokine storm, and endothelial dysfunction. Following virus entry and RAS activation, acute respiratory distress syndrome develops with an oxidative/nitrosative burst. The DNA damage induced by oxidative stress activates poly ADP-ribose polymerase-1 (PARP-1), viral macrodomain of non-structural protein 3, poly (ADP-ribose) glycohydrolase (PARG), and transient receptor potential melastatin type 2 (TRPM2) channel in a sequential manner which results in cell apoptosis or necrosis. In this review, blockers of angiotensin II receptor and/or PARP, PARG, and TRPM2, including vitamin D3, trehalose, tannins, flufenamic and mefenamic acid, and losartan, have been investigated for inhibiting RAS activation and quenching oxidative burst. Moreover, the application of organic and inorganic nanoparticles, including liposomes, dendrimers, quantum dots, and iron oxides, as therapeutic agents for SARS-CoV-2 were fully reviewed. In the present review, the clinical manifestations of COVID-19 are explained by focusing on molecular mechanisms. Potential therapeutic targets, including the RAS signaling pathway, PARP, PARG, and TRPM2, are also discussed in depth.


Subject(s)
COVID-19/drug therapy , COVID-19/therapy , Cytokine Release Syndrome/drug therapy , Nanomedicine/methods , Oxidative Stress/drug effects , Poly (ADP-Ribose) Polymerase-1/metabolism , SARS-CoV-2/drug effects , Apoptosis/drug effects , COVID-19/metabolism , COVID-19/physiopathology , Cholecalciferol/pharmacology , GTPase-Activating Proteins/antagonists & inhibitors , GTPase-Activating Proteins/metabolism , Humans , Poly (ADP-Ribose) Polymerase-1/antagonists & inhibitors , Renin-Angiotensin System/drug effects , SARS-CoV-2/growth & development , SARS-CoV-2/metabolism , TRPM Cation Channels/antagonists & inhibitors , TRPM Cation Channels/metabolism , Tannins/pharmacology , Trehalose/pharmacology
7.
Popul Health Manag ; 24(S1): S26-S34, 2021 02.
Article in English | MEDLINE | ID: covidwho-1236198

ABSTRACT

Laboratory testing is an important component in the diagnosis of respiratory tract infections such as with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, specimen collection not only risks exposure of health care workers and other patients to infection, but also necessitates use of personal protective equipment that may be in short supply during periods of heightened disease activity. Self-collection of nasal or oropharyngeal swabs offers an alternative to address these drawbacks. Although studies in the past decade have demonstrated the utility of this approach for respiratory infections, it has not been widely adopted in routine clinical practice. The rapid spread of coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has focused attention on the need for safe, convenient, timely, and scalable methods for collecting upper respiratory specimens for testing. The goals of this article are to highlight the literature regarding self-collected nasal or oropharyngeal specimens for respiratory pathogen testing; discuss the role of self-collection in helping prevent the spread of the COVID-19 disease from infected patients and facilitating a shift toward "virtual" medicine or telemedicine; and describe the current and future state of self-collection for infectious agents, and the impacts these approaches can have on population health management and disease diagnosis and prevention.


Subject(s)
COVID-19 , Population Health Management , Specimen Handling/methods , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/prevention & control , COVID-19/virology , Child , Child, Preschool , Humans , Infant , Middle Aged , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/prevention & control , Respiratory Tract Infections/virology , SARS-CoV-2 , Self Care , Telemedicine , Young Adult
8.
ACS Biomater Sci Eng ; 7(6): 2150-2176, 2021 Jun 14.
Article in English | MEDLINE | ID: covidwho-1225482

ABSTRACT

Human respiratory viral infections are the leading cause of morbidity and mortality around the world. Among the various respiratory viruses, coronaviruses (e.g., SARS-CoV-2) have created the greatest challenge and most frightening health threat worldwide. Human coronaviruses typically infect the upper respiratory tract, causing illnesses that range from common cold-like symptoms to severe acute respiratory infections. Several promising vaccine formulations have become available since the beginning of 2021. Nevertheless, achievement of herd immunity is still far from being realized. Social distancing remains the only effective measure against SARS-CoV-2 infection. Nanobiotechnology enables the design of nanobiosensors. These nanomedical diagnostic devices have opened new vistas for early detection of viral infections. The present review outlines recent research on the effectiveness of nanoplatforms as diagnostic and antiviral tools against coronaviruses. The biological properties of coronavirus and infected host organs are discussed. The challenges and limitations encountered in combating SARS-CoV-2 are highlighted. Potential nanodevices such as nanosensors, nanobased vaccines, and smart nanomedicines are subsequently presented for combating current and future mutated versions of coronaviruses.


Subject(s)
COVID-19 , Common Cold , Viruses , Antiviral Agents/therapeutic use , Common Cold/drug therapy , Humans , SARS-CoV-2
9.
Colomb Med (Cali) ; 52(1): e7014577, 2021 Mar 18.
Article in English | MEDLINE | ID: covidwho-1207972

ABSTRACT

CASE DESCRIPTION: 32-month-old boy, IgG positive for SARS-CoV-2, presented to the emergency department with dermatologic lesions. CLINICAL FINDINGS: Four days before admission, he presented skin eruptions with redness and pruritus on hands and feet. Generalized papular erythema was evidenced, upper extremities with diffuse erythematosquamous plaques, palmoplantar keratoderma, so he was evaluated by a dermatologist who diagnosed pityriasis rubra pilaris. TREATMENT AND OUTCOME: rehydrating cream, cetirizine 0.5 mg/kg/day every two days, and prednisolone 2 mg/kg/day in the morning. He was discharged after 14 days, the patient presented clinical improvement, but the erythematous lesion persisted on the trunk and extremities. In the evaluation, after three months, the patient did not show the described lesions, evidencing an improvement and clinical resolution of the dermatological problems. CLINICAL RELEVANCE: We report a patient with pityriasis rubra piloris associated with a post-infection by SARS-CoV-2 that had not been described before.


Subject(s)
COVID-19/complications , Pityriasis Rubra Pilaris/etiology , Cetirizine/administration & dosage , Child, Preschool , Glucocorticoids/administration & dosage , Humans , Immunoglobulin G , Male , Pityriasis Rubra Pilaris/diagnosis , Pityriasis Rubra Pilaris/drug therapy , Prednisolone/administration & dosage
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