Dataset Information

In plain sight: the role of alpha-1-antitrypsin in COVID-19 pathogenesis and therapeutics.

ABSTRACT: Entry of SARS-CoV-2 is facilitated by endogenous and exogenous proteases. These proteases proteolytically activate the SARS-CoV-2 spike glycoprotein and are key modulators of virus tropism. We show that SARS-CoV-2 naïve serum exhibits significant inhibition of SARS-CoV-2 entry. We identify alpha-1-antitrypsin (AAT), and to a lesser degree, alpha-2-macroglobulin (A2M) as highly abundant serum protease inhibitors that potently restrict protease-mediated entry of SARS-CoV-2. AAT inhibition of protease-mediated SARS-CoV-2 entry in vitro occurs at concentrations far below what is present in serum and bronchoalveolar tissues, suggesting that AAT effects are physiologically relevant. Moreover, AAT mutations that have been characterized to affect abundance or function are highly prevalent. In addition to the effects that AAT may have on viral entry itself, we argue that the anti-inflammatory and coagulation regulatory activity of AAT have implications for coronavirus disease 2019 (COVID-19) pathogenicity, SARS-CoV-2 tissue restriction, convalescent plasma therapies, and even potentially AAT therapy.

SUBMITTER: Oguntuyo KY

PROVIDER: S-EPMC7430570 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

Alpha-1-antitrypsin and its variant-dependent role in COVID-19 pathogenesis.

Stevens Christian S CS Oguntuyo Kasopefoluwa Y KY Oguntuyo Kasopefoluwa Y KY Kowdle Shreyas S Kowdle Shreyas S Brambilla Luca L Brambilla Luca L Haas Griffin G Gowlikar Aditya A Siddiquey Mohammed Na MN Schilke Robert M RM Woolard Matthew D MD Zhang Hongbo H Acklin Joshua A JA Ikegame Satoshi S Huang Chuan-Tien CT Lim Jean K JK Cross Robert W RW Geisbert Thomas W TW Ivanov Stanimir S SS Kamil Jeremy P JP Lee Benhur B

bioRxiv : the preprint server for biology 20230508

<h4>Rationale</h4>SARS-CoV-2 entry into host cells is facilitated by endogenous and exogenous proteases that proteolytically activate the spike glycoprotein and antiproteases inhibiting this process. Understanding the key actors in viral entry is crucial for advancing knowledge of virus tropism, pathogenesis, and potential therapeutic targets.<h4>Objectives</h4>We aimed to investigate the role of naïve serum and alpha-1-antitrypsin (AAT) in inhibiting protease-mediated SARS-CoV-2 entry and explo ...[more]

PMID: 32817940

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Project description:Individuals cope with stress using multiple strategies, yet studies of coping profiles are rare. We draw data from a longitudinal study of Australian men (n = 272; 30-37 years), assessed before (T1) and during (T2) a nation-wide COVID-19 lockdown. We aimed to: (1) identify men's multi-strategy coping profiles before and during the pandemic; (2) assess cross-sectional (T1-T1, T2-T2) and prospective (T1-T2) associations between profiles and symptoms of psychological distress (stress, anxiety, depression, and anger); and (3) examine relationships between coping profiles and appraisals of pandemic-related stressors and options for coping. In latent profile analyses of 14 coping strategies, three profiles emerged that were largely consistent across T1 and T2: (1) Relaxed Copers (low use of all strategies), (2) Approach Copers, and (3) Dual Copers (high avoidant and moderate-high approach-oriented strategies). Compared to Relaxed and Approach Copers, men who were Dual Copers had elevated psychological distress cross-sectionally before (T1) and during (T2) the pandemic, but not prospectively. Post hoc analyses suggested this was because many men changed coping profiles in the context of the pandemic. Men with stable (T1-T2) or new (T2 only) Dual Coping profiles experienced greater psychological distress and more negative appraisals of pandemic stressors and options for coping. In sum, at the sample level, the composition of men's coping profiles and associations with mental health risk were relatively stable over time and contexts; however, many men appeared to respond to pandemic conditions by changing coping profile groups, with mostly positive mental health outcomes. Of concern were men who adopted more avoidant strategies (e.g., denial, self-distraction, disengagement, substance use, and self-blame) under pandemic conditions. These Dual Coper men also engaged in commonly observable approach-oriented behaviours (e.g., planning, active coping, humour, seeking practical social support) that may mask their vulnerability to mental health risk. Our findings highlight the clinical importance of enquiring about escalating or frequent avoidant coping even in the presence of more active and interactive approach-oriented behaviours.

Dataset Information

In plain sight: the role of alpha-1-antitrypsin in COVID-19 pathogenesis and therapeutics.

Publications

Alpha-1-antitrypsin and its variant-dependent role in COVID-19 pathogenesis.

Similar Datasets

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