Respiratory syncytial virus infects peripheral and spinal nerves and induces chemokine-mediated neuropathy.

Respiratory syncytial virus (RSV) primarily infects the respiratory epithelium, but growing evidence suggests it may also be responsible for neurological sequelae. In 3D microphysiological peripheral nerve cultures, RSV infected neurons, macrophages, and dendritic cells along two distinct trajectories depending on the initial viral load. Low-level infection was transient, primarily involved macrophages, and induced moderate chemokine release with transient neural hypersensitivity. Infection with higher viral loads was persistent, infected neuronal cells in addition to monocytes, and induced robust chemokine release followed by progressive neurotoxicity. In spinal cord cultures, RSV infected microglia and dendritic cells but not neurons, producing a moderate chemokine expression pattern. The persistence of infection was variable but could be identified in dendritic cells as long as 30 days post-inoculation. This study suggests that RSV can disrupt neuronal function directly through infection of peripheral neurons and indirectly through infection of resident monocytes, and inflammatory chemokines likely mediate both mechanisms.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Dose, Infection, and Disease Outcomes for Coronavirus Disease 2019 (COVID-19): A Review.

The relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dose, infection, and coronavirus disease 2019 (COVID-19) outcomes remains poorly understood. This review summarizes the existing literature regarding this issue, identifies gaps in current knowledge, and suggests opportunities for future research. In humans, host characteristics, including age, sex, comorbidities, smoking, and pregnancy, are associated with severe COVID-19. Similarly, in animals, host factors are strong determinants of disease severity, although most animal infection models manifest clinically with mild to moderate respiratory disease. The influence of variants of concern as it relates to infectious dose, consequence of overall pathogenicity, and disease outcome in dose-response remains unknown. Epidemiologic data suggest a dose-response relationship for infection contrasting with limited and inconsistent surrogate-based evidence between dose and disease severity. Recommendations include the design of future infection studies in animal models to investigate inoculating dose on outcomes and the use of better proxies for dose in human epidemiology studies.

The CNS/PNS Extracellular Matrix Provides Instructive Guidance Cues to Neural Cells and Neuroregulatory Proteins in Neural Development and Repair.

BACKGROUND: The extracellular matrix of the PNS/CNS is unusual in that it is dominated by glycosaminoglycans, especially hyaluronan, whose space filling and hydrating properties make essential contributions to the functional properties of this tissue. Hyaluronan has a relatively simple structure but its space-filling properties ensure micro-compartments are maintained in the brain ultrastructure, ensuring ionic niches and gradients are maintained for optimal cellular function. Hyaluronan has cell-instructive, anti-inflammatory properties and forms macro-molecular aggregates with the lectican CS-proteoglycans, forming dense protective perineuronal net structures that provide neural and synaptic plasticity and support cognitive learning. AIMS: To highlight the central nervous system/peripheral nervous system (CNS/PNS) and its diverse extracellular and cell-associated proteoglycans that have cell-instructive properties regulating neural repair processes and functional recovery through interactions with cell adhesive molecules, receptors and neuroregulatory proteins. Despite a general lack of stabilising fibrillar collagenous and elastic structures in the CNS/PNS, a sophisticated dynamic extracellular matrix is nevertheless important in tissue form and function. CONCLUSIONS: This review provides examples of the sophistication of the CNS/PNS extracellular matrix, showing how it maintains homeostasis and regulates neural repair and regeneration.

Review of Alterations in Perlecan-Associated Vascular Risk Factors in Dementia.

Perlecan is a heparan sulfate proteoglycan protein in the extracellular matrix that structurally and biochemically supports the cerebrovasculature by dynamically responding to changes in cerebral blood flow. These changes in perlecan expression seem to be contradictory, ranging from neuroprotective and angiogenic to thrombotic and linked to lipid retention. This review investigates perlecan's influence on risk factors such as diabetes, hypertension, and amyloid that effect Vascular contributions to Cognitive Impairment and Dementia (VCID). VCID, a comorbidity with diverse etiology in sporadic Alzheimer's disease (AD), is thought to be a major factor that drives the overall clinical burden of dementia. Accordingly, changes in perlecan expression and distribution in response to VCID appears to be injury, risk factor, location, sex, age, and perlecan domain dependent. While great effort has been made to understand the role of perlecan in VCID, additional studies are needed to increase our understanding of perlecan's role in health and in cerebrovascular disease.

Roles of blood-brain barrier integrins and extracellular matrix in stroke.

Ischemicstroke is a leading cause of death and disability in the United States, but recent advances in treatments [i.e., endovascular thrombectomy and tissue plasminogen activator (t-PA)] that target the stroke-causing blood clot, while improving overall stroke mortality rates, have had much less of an impact on overall stroke morbidity. This may in part be attributed to the lack of therapeutics targeting reperfusion-induced injury after the blood clot has been removed, which, if left unchecked, can expand injury from its core into the surrounding at risk tissue (penumbra). This occurs in two phases of increased permeability of the blood-brain barrier, a physical barrier that under physiologic conditions regulates brain influx and efflux of substances and consists of tight junction forming endothelial cells (and transporter proteins), astrocytes, pericytes, extracellular matrix, and their integrin cellular receptors. During, embryonic development, maturity, and following stroke reperfusion, cerebral vasculature undergoes significant changes including changes in expression of integrins and degradation of surrounding extracellular matrix. Integrins, heterodimers with α and ß subunits, and their extracellular matrix ligands, a collection of proteoglycans, glycoproteins, and collagens, have been modestly studied in the context of stroke compared with other diseases (e.g., cancer). In this review, we describe the effect that various integrins and extracellular matrix components have in embryonic brain development, and how this changes in both maturity and in the poststroke environment. Particular focus will be on how these changes in integrins and the extracellular matrix affect blood-brain barrier components and their potential as diagnostic and therapeutic targets for ischemic stroke.

Interleukin 1 alpha administration is neuroprotective and neuro-restorative following experimental ischemic stroke.

BACKGROUND: Stroke remains a leading cause of death and disability worldwide despite recent treatment breakthroughs. A primary event in stroke pathogenesis is the development of a potent and deleterious local and peripheral inflammatory response regulated by the pro-inflammatory cytokine interleukin-1 (IL-1). While the role of IL-1ß (main released isoform) has been well studied in stroke, the role of the IL-1α isoform remains largely unknown. With increasing utilization of intravenous tissue plasminogen activator (t-PA) or thrombectomy to pharmacologically or mechanically remove ischemic stroke causing blood clots, respectively, there is interest in pairing successful cerebrovascular recanalization with neurotherapeutic pharmacological interventions (Fraser et al., J Cereb Blood Flow Metab 37:3531-3543, 2017; Hill et al., Lancet Neurol 11:942-950, 2012; Amaro et al., Stroke 47:2874-2876, 2016). METHODS: Transient stroke was induced in mice via one of two methods. One group of mice were subjected to tandem ipsilateral common carotid artery and middle cerebral artery occlusion, while another group underwent the filament-based middle cerebral artery occlusion. We have recently developed an animal model of intra-arterial (IA) drug administration after recanalization (Maniskas et al., J Neurosci Met 240:22-27, 2015). Sub groups of the mice were treated with either saline or Il-1α, wherein the drug was administered either acutely (immediately after surgery) or subacutely (on the third day after stroke). This was followed by behavioral and histological analyses. RESULTS: We now show in the above-mentioned mouse stroke models (transient tandem ipsilateral common carotid artery (CCA) and middle cerebral artery occlusion (MCA) occlusion, MCA suture occlusion) that IL-1α is neuroprotective when acutely given either intravenously (IV) or IA at low sub-pathologic doses. Furthermore, while IV administration induces transient hemodynamic side effects without affecting systemic markers of inflammation, IA delivery further improves overall outcomes while eliminating these side effects. Additionally, we show that delayed/subacute IV IL-1α administration ameliorates functional deficit and promotes neurorepair. CONCLUSIONS: Taken together, our present study suggests for the first time that IL-1α could, unexpectedly, be an effective ischemic stroke therapy with a broad therapeutic window.

Evaluation of Patients with High National Institutes of Health Stroke Scale as Thrombectomy Candidates Using the Kentucky Appalachian Stroke Registry.

INTRODUCTION: Mechanical thrombectomy has become standard of care for emergent large vessel occlusive stroke. Estimates of incidence for thrombectomy eligibility vary significantly. National Institutes of Health Stroke Scale (NIHSS) of 10 or greater is highly predictive of large vessel occlusion. Using our Kentucky Appalachian Stroke Registry (KApSR), we evaluated temporal trends in stroke admissions with NIHSS ≥10 to determine patient characteristics among that group along with effects and needs in thrombectomy utilization. METHODS: Using the KApSR database that captures patients throughout the Appalachian region in our stroke network, we evaluated patients admitted with ischemic stroke with NIHSS ≥10. We recorded demographics, comorbidities, treatment (thrombectomy, decompressive craniectomy), and county of origin. Change in NIHSS from admission to discharge was used as an indicator of inpatient outcome. RESULTS: Between 2010 and 2016, 1,510 patients were admitted with NIHSS ≥10. 87.2% had high blood pressure, 69.6% had dyslipidemia, and 41.7% used tobacco. There were significant sex differences in the types of patients presenting with NIHSS ≥10 with females being older on average and having more atrial fibrillation and obesity. There was an increase in thrombectomy utilization from 2010 to 2016, but only 7.5% of the potentially eligible patients underwent the procedure. In comparison to the period 2010-2014, the 2015-2016 period had higher rates of obesity and tobacco abuse. CONCLUSION: Among patients with significant burden of ischemic stroke, the most common coexisting medical condition was high blood pressure. Patients who underwent thrombectomy had significantly better inpatient clinical improvement. These data support the need to maximize utilization of thrombectomy along with need to devote increased resources on modifiable stroke risk factors.

IL-1alpha induces angiogenesis in brain endothelial cells in vitro: implications for brain angiogenesis after acute injury.

Inflammation is a major contributor to neuronal injury and is associated with poor outcome after acute brain injury such as stroke. The pro-inflammatory cytokine interleukin (IL)-1 is a critical regulator of cerebrovascular inflammation after ischemic injury, mainly through action of both of its isoforms, IL-1α and IL-1ß, at the brain endothelium. In contrast, the differential action of these ligands on endothelial activation and post-stroke angiogenesis is largely unknown. Here, we demonstrate that IL-1α is chronically elevated in the brain after experimental stroke suggesting that it is present during post-stroke angiogenic periods. Furthermore, we demonstrate that IL-1α is a potent mediator of endothelial activation and inducer of angiogenic markers in endothelial cells in vitro. Using brain endothelial cell lines, we found that IL-1α was significantly more potent than IL-1ß at inducing endothelial cell activation, as measured by expression of the pro-angiogenic chemokine CXCL-1. IL-1α also induced strong expression of the angiogenic mediator IL-6 in a concentration-dependent manner. Furthermore, IL-1α induced significant proliferation and migration of endothelial cells, and promoted formation of tube-like structures that are established key hallmarks of angiogenesis in vitro. Finally, all of those responses were blocked by the IL-1 receptor antagonist (IL-1RA). In conclusion, our data highlights a potential new role for IL-1 in brain repair mechanisms and identifies IL-1α as a potential new therapy to promote post-stroke angiogenesis. Inflammation is a major contributor to neuronal injury and is associated with poor outcome after neurotrauma. We demonstrate that cytokine IL-1α is chronically elevated in the brain after experimental stroke suggesting that it is present chronically post-stroke. We demonstrate that IL-1α is a potent mediator of endothelial activation and inducer of angiogenic markers in endothelial cells. Our data highlights a new role for IL-1 in brain repair mechanisms and identifies IL-1α as a potential therapy to promote post-stroke angiogenesis.

The potential role of perlecan domain V as novel therapy in vascular dementia.

Vascular dementia (VaD) is the second most common cause of dementia and leads to a decline in cognitive thinking via conditions that lead to blockage or reduced blood flow to the brain. It is a poorly understood disease, and the changes that occur are often linked to other types of dementia such as Alzheimer's disease. To date, there are no approved therapies or drugs to treat the symptoms of VaD, even though there is some evidence of drugs approved for Alzheimer's that might have some benefit in patients diagnosed with VaD. The altered blood flow that precedes VaD may result in compensatory mechanisms, such as angiogenesis, to increase blood flow in the brain. Angiogenesis, the process of new blood vessel formations from pre-existing ones, involves several pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and is regulated by a variety of growth factors from neurons, astrocytes, and pericytes in the brain as well the extracellular matrix (ECM). The ECM highly regulates angiogenesis and other processes in the brain. One such ECM component is the heparan sulfate proteoglycan perlecan and its bioactive region, Domain V (DV). Here we discuss the potential role of DV as a novel therapy to treat VaD.

Senescence and SASP Are Potential Therapeutic Targets for Ischemic Stroke.

Aging is a known co-morbidity of ischemic stroke with its risk and severity increasing every year past 55+. While many of the current stroke therapies have shown success in reducing mortality, post-stroke morbidity has not seen the same substantial reduction. Recently, the involvement of cellular senescence and SASP in brain injury and neurological degeneration has been recognized. Ischemic injury causes oxidative stress and mitochondrial damage that induces senescence through the activation of p21 and p16 pathways, ultimately leading to synthesis and release of senescence-associated secretory phenotype (SASP). This ischemic event causes stress-induced premature senescence (SIPS), aging the brain decades beyond the standard biological age due to an increase in senescent cells in the ischemic core and ipsilateral hemisphere. Therefore, therapies that target the senescent cells and SASP, including senolytics, senomorphic drugs, stem cell therapies, and other cell-specific interventions, may be a new path for stroke treatment.

Prevalence of MTHFR Polymorphisms in Patients With Hypermobile Ehlers-Danlos Syndrome and Hypermobile Spectrum Disorders in a US Hypermobility Clinic.

OBJECTIVE: Hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) are characterized by joint hypermobility, joint subluxations and dislocations, hyperextensible skin, and chronic and progressive multiorgan comorbidities. Diagnosing hEDS and HSD is difficult because of variable phenotypes and unknown genetic etiology. In our clinic, we observed many patients with hEDS and HSD with a high serum level of unmetabolized folate, which suggests that hypermobility may be linked to methylenetetrahydrofolate reductase (MTHFR)-mediated folate metabolism. The present study aims to examine the prevalence of MTHFR polymorphisms, C677T and A1298C, among patients with hEDS and HSD. METHODS: Clinical and demographic information of patients visiting our hypermobility clinic from January 2023 to July 2023 were retrospectively reviewed. Continuous variables were reported as mean ± SD and range, whereas categorical variables were reported as total count and percentage. RESULTS: Among 157 patients, 93% of patients were female patients, 52.2% were diagnosed with hEDS, and 47.8% were diagnosed with HSD. Interestingly, 85% of the patients had MTHFR C677T and/or A1298C polymorphisms in heterozygous or homozygous state. MTHFR 677CT/TT genotype was present in 52.9% of cases, and 49.7% of patients had 1298AC/CC genotype. In addition,14% of patients with hypermobility exhibited MTHFR 677TT genotype, 10.2% showed 1298CC genotype, and 17.2% displayed combined heterozygosity, collectively representing 41.4% hypermobile patients with two copies of MTHFR variant alleles. CONCLUSION: There is a high prevalence of MTHFR polymorphisms among patients with hypermobility, which supports the hypothesis that hypermobility may be dependent on folate status.

Molecular interactions between perlecan LG3 and the SARS-CoV-2 spike protein receptor binding domain.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a global health crisis with significant clinical morbidity and mortality. While angiotensin-converting enzyme 2 (ACE2) is the primary receptor for viral entry, other cell surface and extracellular matrix proteins may also bind to the viral receptor binding domain (RBD) within the SARS-CoV-2 spike protein. Recent studies have implicated heparan sulfate proteoglycans, specifically perlecan LG3, in facilitating SARS-CoV-2 binding to ACE2. However, the role of perlecan LG3 in SARS-CoV-2 pathophysiology is not well understood. In this study, we investigated the binding interactions between the SARS-CoV-2 spike protein RBD and perlecan LG3 through molecular modeling simulations and surface plasmon resonance (SPR) experiments. Our results indicate stable binding between LG3 and SARS-CoV-2 spike protein RBD, which may potentially enhance RBD-ACE2 interactions. These findings shed light on the role of perlecan LG3 in SARS-CoV-2 infection and provide insight into SARS-CoV-2 pathophysiology and potential therapeutic strategy for COVID-19.

Selective deletion of interleukin-1 alpha in microglia does not modify acute outcome but regulates neurorepair processes after experimental ischemic stroke.

Inflammation is a key contributor to stroke pathogenesis and exacerbates brain damage leading to poor outcome. Interleukin-1 (IL-1) is an important regulator of post-stroke inflammation, and blocking its actions is beneficial in pre-clinical stroke models and safe in the clinical setting. However, the distinct roles of the two major IL-1 receptor type 1 agonists, IL-1α and IL-1ß, and the specific role of IL-1α in ischemic stroke remain largely unknown. Here we show that IL-1α and IL-1ß have different spatio-temporal expression profiles in the brain after experimental stroke, with early microglial IL-1α expression (4 h) and delayed IL-1ß expression in infiltrated neutrophils and a small microglial subset (24-72 h). We examined for the first time the specific role of microglial-derived IL-1α in experimental permanent and transient ischemic stroke through microglial-specific tamoxifen-inducible Cre-loxP-mediated recombination. Microglial IL-1α deletion did not influence acute brain damage, cerebral blood flow, IL-1ß expression, neutrophil infiltration, microglial nor endothelial activation after ischemic stroke. However, microglial IL-1α knock out (KO) mice showed reduced peri-infarct vessel density and reactive astrogliosis at 14 days post-stroke, alongside long-term impaired functional recovery. Our study identifies for the first time a critical role for microglial IL-1α on neurorepair and functional recovery after stroke, highlighting the importance of targeting specific IL-1 mechanisms in brain injury to develop more effective therapies.

VEGFA Isoforms as Pro-Angiogenic Therapeutics for Cerebrovascular Diseases.

Therapeutic angiogenesis has long been considered a viable treatment for vasculature disruptions, including cerebral vasculature diseases. One widely-discussed treatment method to increase angiogenesis is vascular endothelial growth factor (VEGF) A. In animal models, treatment with VEGFA proved beneficial, resulting in increased angiogenesis, increased neuronal density, and improved outcome. However, VEGFA administration in clinical trials has thus far failed to replicate the promising results seen in animal models. The lack of beneficial effects in humans and the difficulty in medicinal translation may be due in part to administration methods and VEGFA's ability to increase vascular permeability. One solution to mitigate the side effects of VEGFA may be found in the VEGFA isoforms. VEGFA is able to produce several different isoforms through alternative splicing. Each VEGFA isoform interacts differently with both the cellular components and the VEGF receptors. Because of the different biological effects elicited, VEGFA isoforms may hold promise as a tangible potential therapeutic for cerebrovascular diseases.

Bilateral Carotid Artery Stenosis and Cerebral Blood Flow Outcomes.

Bilateral carotid artery stenosis (BCAS) is a valid approach for modeling vascular dementia (VaD) in mice as it induces cerebral hypoperfusion and produces white matter degeneration and cognitive impairment. VaD is one of the major causes of cognitive impairment and currently has no approved therapy; hence its preclinical modeling is warranted for investigating potential therapeutic compounds. BCAS enables the characterization of brain pathology and associated cognitive phenotype of VaD. In this chapter, we describe the surgical method of inducing BCAS in mice, using titanium micro-coils, and we report cerebral blood flow changes before and after surgical induction as well as some histological findings in the corpus callosum of diabetic mice subjected to long-term BCAS.

Promising Cerebral Blood Flow Enhancers in Acute Ischemic Stroke.

Ischemic stroke presents a major global economic and public health burden. Although recent advances in available endovascular therapies show improved functional outcome, a good number of stroke patients are either ineligible or do not have access to these treatments. Also, robust collateral flow during acute ischemic stroke independently predicts the success of endovascular therapies and the outcome of stroke. Hence, adjunctive therapies for cerebral blood flow (CBF) enhancement are urgently needed. A very clear overview of the pial collaterals and the role of genetics are presented in this review. We review available evidence and advancement for potential therapies aimed at improving CBF during acute ischemic stroke. We identified heme-free soluble guanylate cyclase activators; Sanguinate, remote ischemic perconditioning; Fasudil, S1P agonists; and stimulation of the sphenopalatine ganglion as promising potential CBF-enhancing therapeutics requiring further investigation. Additionally, we outline and discuss the critical steps required to advance research strategies for clinically translatable CBF-enhancing agents in the context of acute ischemic stroke models.

Perlecan: a review of its role in neurologic and musculoskeletal disease.

Perlecan is a 500 kDa proteoglycan residing in the extracellular matrix of endothelial basement membranes with five distinct protein domains and three heparan sulfate chains. The complex structure of perlecan and the interaction it has with its local environment accounts for its various cellular and tissue-related effects, to include cartilage, bone, neural and cardiac development, angiogenesis, and blood brain barrier stability. As perlecan is a key contributor to extracellular matrix health involved in many tissues and processes throughout the body, dysregulation of perlecan has the potential to contribute to various neurological and musculoskeletal diseases. Here we review key findings associated with perlecan dysregulation in the context of disease. This is a narrative review article examining perlecan’s role in diseases of neural and musucloskeletal pathology and its potential as a therapeutic index. Literature searches were conducted on the PubMed database, and were focused on perlecan's impact in neurological disease, to include ischemic stroke, Alzheimer's Disease (AD) and brain arteriovenous malformation (BAVM), as well as musculoskeletal pathology, including Dyssegmental Dysplasia Silverman-Handmaker type (DDSH), Schwartz-Jampel syndrome (SJS), sarcopenia, and osteoarthritis (OA). PRISMA guidelines were utilized in the search and final selection of articles.Increased perlecan levels were associated with sarcopenia, OA, and BAVM, while decreased perlecan was associated with DDSH, and SJS. We also examined the therapeutic potential of perlecan signaling in ischemic stroke, AD, and osteoarthritic animal models. Perlecan experimentally improved outcomes in such models of ischemic stroke and AD, and we found that it may be a promising component of future therapeutics for such pathology. In treating the pathophysiology of sarcopenia, OA, and BAVM, inhibiting the effect of perlecan may be beneficial. As perlecan binds to both α-5 integrin and VEGFR2 receptors, tissue specific inhibitors of these proteins warrant further study. In addition, analysis of experimental data revealed promising insight into the potential uses of perlecan domain V as a broad treatment for ischemic stroke and AD. As these diseases have limited therapeutic options, further study into perlecan or its derivatives and its potential to be used as novel therapeutic for these and other diseases should be seriously considered.

The Potential Role of Integrin Signaling in Memory and Cognitive Impairment.

Dementia currently has no cure and, due to the increased prevalence and associated economic and personal burden of this condition, current research efforts for the development of potential therapies have intensified. Recently, targeting integrins as a strategy to ameliorate dementia and other forms of cognitive impairment has begun to gain traction. Integrins are major bidirectional signaling receptors in mammalian cells, mediating various physiological processes such as cell-cell interaction and cell adhesion, and are also known to bind to the extracellular matrix. In particular, integrins play a critical role in the synaptic transmission of signals, hence their potential contribution to memory formation and significance in cognitive impairment. In this review, we describe the physiological roles that integrins play in the blood-brain barrier (BBB) and in the formation of memories. We also provide a clear overview of how integrins are implicated in BBB disruption following cerebral pathology. Given that vascular contributions to cognitive impairment and dementia and Alzheimer's' disease are prominent forms of dementia that involve BBB disruption, as well as chronic inflammation, we present current approaches shown to improve dementia-like conditions with integrins as a central focus. We conclude that integrins are vital in memory formation and that their disruption could lead to various forms of cognitive impairment. While further research to understand the relationships between integrins and memory is needed, we propose that the translational relevance of research efforts in this area could be improved through the use of appropriately aged, comorbid, male and female animals.

Effect of acetic acid inactivation of SARS-CoV-2.

Effective measures are needed to prevent the spread and infectivity of SARS-CoV-2 that causes COVID-19. Chemical inactivation may help to prevent the spread and transmission of this and other viruses. Hence, we tested the SARS-CoV-2 antiviral activity of acetic acid, the main component of vinegar, in vitro. Inactivation and binding assays suggest that acetic acid is virucidal. We found that 6% acetic acid, a concentration typically found in white distilled vinegar, effectively inactivated SARS-CoV-2 after 15-min incubation with a complete loss of replication of competent virus as measured by TCID50. Transmission electron microscopy further demonstrated that 6% acetic acid disrupts SARS-CoV-2 virion structure. In addition, 6% acetic acid significantly inhibits and disrupts the binding of SARS-CoV-2 spike protein binding to ACE2, the primary SARS-CoV-2 cell receptor, after contact with spike protein for 5, 10, 30 and 60 minutes incubation. Taken together, our findings demonstrate that acetic acid possesses inactivating activity against SARS-CoV-2 and may represent a safe alternative to commonly used chemical disinfectants to effectively control the spread of SARS-CoV-2.

Corrigendum to "Folate-dependent hypermobility syndrome: A proposed mechanism and diagnosis" [Heliyon 9 (4), (April 2023) Article e15387].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e15387.].