Insight into the role of clathrin-mediated endocytosis inhibitors in SARS-CoV-2 infection.

Emergence of SARS-CoV-2 variants warrants sustainable efforts to upgrade both the diagnostic and therapeutic protocols. Understanding the details of cellular and molecular basis of the virus-host cell interaction is essential for developing variant-independent therapeutic options. The internalization of SARS-CoV-2, into lung epithelial cells, is mediated by endocytosis, especially clathrin-mediated endocytosis (CME). Although vaccination is the gold standard strategy against viral infection, selective inhibition of endocytic proteins, complexes, and associated adaptor proteins may present a variant-independent therapeutic strategy. Although clathrin and/or dynamins are the most important proteins involved in CME, other endocytic mechanisms are clathrin and/or dynamin independent and rely on other proteins. Moreover, endocytosis implicates some subcellular structures, like plasma membrane, actin and lysosomes. Also, physiological conditions, such as pH and ion concentrations, represent an additional factor that mediates these events. Accordingly, endocytosis related proteins are potential targets for small molecules that inhibit endocytosis-mediated viral entry. This review summarizes the potential of using small molecules, targeting key proteins, participating in clathrin-dependent and -independent endocytosis, as variant-independent antiviral drugs against SARS-CoV-2 infection. The review takes two approaches. The first outlines the potential role of endocytic inhibitors in preventing endocytosis-mediated viral entry and its mechanism of action, whereas in the second computational analysis was implemented to investigate the selectivity of common inhibitors against endocytic proteins in SARS-CoV-2 endocytosis. The analysis revealed that remdesivir, methyl-ß-cyclodextrin, rottlerin, and Bis-T can effectively inhibit clathrin, HMG-CoA reductase, actin, and dynamin I GTPase and are more potent in inhibiting SARS-CoV-2 than chloroquine. CME inhibitors for SARS-CoV-2 infection remain understudied.

Propolis efficacy on SARS-COV viruses: a review on antimicrobial activities and molecular simulations.

This current study review provides a brief review of a natural bee product known as propolis and its relevance toward combating SARS-CoV viruses. Propolis has been utilized in medicinal products for centuries due to its excellent biological properties. These include anti-oxidant, immunomodulatory, anti-inflammatory, anti-viral, anti-fungal, and bactericidal activities. Furthermore, studies on molecular simulations show that flavonoids in propolis may reduce viral replication. While further research is needed to validate this theory, it has been observed that COVID-19 patients receiving propolis show earlier viral clearance, enhanced symptom recovery, quicker discharge from hospitals, and a reduced mortality rate relative to other patients. As a result, it appears that propolis could probably be useful in the treatment of SARS-CoV-2-infected patients. Therefore, this review sought to explore the natural properties of propolis and further evaluated past studies that investigated propolis as an alternative product for the treatment of COVID-19 symptoms. In addition, the review also highlights the possible mode of propolis action as well as molecular simulations of propolis compounds that may interact with the SARS-CoV-2 virus. The activity of propolis compounds in decreasing the impact of COVID-19-related comorbidities, the possible roles of such compounds as COVID-19 vaccine adjuvants, and the use of nutraceuticals in COVID-19 treatment, instead of pharmaceuticals, has also been discussed.

Epilepsy surgery in PCDH 19 related developmental and epileptic encephalopathy: A case report.

We report a female child with PCDH19 related developmental and epileptic encephalopathy with drug-resistant seizures, cognitive and language impairment, autism spectrum disorder and sleep dysfunction. Her seizures, which started at 10 months of age, were resistant to multiple anti-seizure medications. Developmental stagnation followed by regression occurred after the onset of recurrent seizures. Her ictal EEGS suggested left temporal lobe origin for her recorded seizures. MRI upon expert re-review showed a subtle abnormality in the left temporal lobe. In view of the severe nature and frequency of her seizures, a left temporal lobectomy was undertaken at the age of 2 years and 3 months. Though her seizure outcome was Engel class 3, her seizure frequency and severity were significantly reduced. She has been seizure-free for 10 months at her last outpatient assessment when she was 4 years and 8 months of age (2 years and 5 months after epilepsy surgery). However she recently had an admission for COVID19 infection, with a breakthrough cluster of seizures. Her developmental trajectory changed, though she is making good progress with her cognitive and language skills.

Cerebral arterial and venous thrombosis due to COVID-19 vaccine-induced immune thrombotic thrombocytopenia.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) rarely develops after many COVID-19 vaccines. A 51-year-old woman re-presented to hospital with a 4 day history of headache, vomiting, diarrhoea and left calf pain, 11 days after her first dose of ChAdOx1nCoV-19 (AstraZenica) vaccine. Her neurological examination was normal. Blood tests demonstrated a low platelet count, raised D-dimer and CRP, and a positive heparin/anti-PF4 antibody assay. CT venogram demonstrated widespread cerebral venous sinus thrombosis. She was commenced on fondaparinux and intravenous immunoglobulins. The following day she developed an asymmetric quadriplegia and aphasia. CT angiogram demonstrated new bilateral cervical internal carotid artery (ICA) thrombi. She underwent stent-retriever mechanical thrombectomy of bilateral ICA and cerebral venous sinuses. Next day she had right hemiparesis and expressive dysphasia, which are improving. Thromboses due to VITT can progress rapidly to involve cerebral arteries and venous sinuses, and may warrant urgent arterial and venous thrombectomy to reduce morbidity and mortality.

CONFRONT: Cloud-fog-dew based monitoring framework for COVID-19 management

In the recent times, the IoT (Internet of Things) enabled devices and applications have seen a rapid growth in various sectors including healthcare. The ability of low-cost connected sensors to cover large areas makes it a potential tool in the fight against pandemics, like COVID-19. The COVID-19 has posed a formidable challenge for the developing countries, like India, which need to cater to large population base with limited health infrastructure. In this paper, we proposed a  Cloud-fog-dew based mOnitoriNg Framework foR cOvid-19 maNagemenT, called CONFRONT. This cloud-fog-dew based healthcare model may help in preliminary diagnosis and also in monitoring patients while they are in quarantine facilities or home based treatments. The fog architecture ensures that the model is suited for real-time scenarios while keeping the bandwidth requirements low. To analyse large scale COVID-19 statistics data for extracting aggregate information of the disease spread, the cloud servers are leveraged due to its scalable computational and storage capabilities. The dew architecture ensures that the application is available at a limited scale even when cloud connectivity is lost, leading to a faster uptime for the application. A low cost wearable device consisting of heterogeneous sensors has also been designed and fabricated to realize the proposed framework.

Does Climate Variability Impact COVID-19 Outbreak? An Enhanced Semantics-Driven Theory-Guided Model.

COVID-19, a life-threatening infection by novel coronavirus, has broken out as a pandemic since December 2019. Eventually, with the aim of helping the World Health Organization and other health regulators to combat COVID-19, significant research effort has been exerted during last several months to analyze how the various factors, especially the climatic aspects, impact on the spread of this infection. However, due to insufficient test and lack of data transparency, these research findings, at times, are found to be inconsistent as well as conflicting. In our work, we aim to employ a semantics-driven probabilistic framework for analyzing the causal influence as well as the impact of climate variability on the COVID-19 outbreak. The idea here is to tackle the data inadequacy and uncertainty issues using probabilistic graphical analysis along with embedded technology of incorporating semantics from climatological domain. Furthermore, the theoretical guidance from epidemiological model additionally helps the framework to better capture the pandemic characteristics. More significantly, we further enhance the impact analysis framework with an auxiliary module of measuring semantic relatedness on regional basis, so as to realistically account for the existence of multiple climate types within a single spatial region. This added notion of regional semantic relatedness further helps us to attain improved probabilistic analysis for modeling the climatological impact on this disease outbreak. Experimentation with COVID-19 datasets over 15 states (or provinces) belonging to varying climate regions in India, demonstrates the effectiveness of our semantically-enhanced theory-guided data-driven approach. It is worth noting that our proposed framework and the relevant semantic analyses are generic enough for intelligent as well as explainable impact analysis in many other application domains, by introducing minimal augmentation.

An Overview on the Epidemiology and Immunology of COVID-19.

Coronaviruses are a large family of viruses that cause illnesses ranging from the common cold to more severe diseases such as Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS), and the 2019 novel coronavirus infection (COVID-19). Currently, there is no analyzed data to examine the outbreak of COVID-19 by continent and no determination of prevalence trends; this article reviews COVID-19 epidemiology and immunology. Original research, reviews, governmental databases, and treatment guidelines are analyzed to present the epidemiology and immunology of COVID-19. Reports from patients who were COVID-19 infected showed typical symptoms of neutrophilia, lymphopenia, and increased systemic inflammatory proteins of IL-6 and C reactive protein (CRP). These observations agree with the results of severe conditions of MERS or lethal cases of SARS, in which there is an increased presence of neutrophils and macrophages in the airways. Additionally, analyzed data showed that Europe (49.37%), the Americas (27.4%), and Eastern Mediterranean (10.07%) had the most cumulative total per 100,000 population confirmed cases, and Africa (6.9%), Western Pacific (3.46%), and South-East Asia (2.72%) had the lowest cumulative total per 100,000 population confirmed cases. In general, the trend lines showed that the number of confirmed cases (cumulative total) and deaths (cumulative total) would decrease eventually.

Antimicrobial Resistance Threats in the emerging COVID-19 pandemic: Where do we stand?

Antimicrobial resistance (AMR) continues to exert a substantial toll on the global health and world economy and is now expected to be hidden by COVID-19 for a while. The wrong consumption of antibiotics during the COVID-19 pandemic will raise disastrous effects on AMR management and antibiotic stewardship programs. This is related to the concerns extrapolated due to an increase in mortality rates in patients with bacterial coinfections. Importantly, the immune system of COVID-19 patients in regions with high AMR may be fighting on two fronts altogether, the virus and MDR bacteria. Current control policies to manage AMR and prioritization of antibiotic stewardship plans are mandatory during this pandemic. This review aims to discuss the rising concerns of the excess use of antibiotics in COVID-19 patients highlighting the role of bacterial coinfections in these patients. Types of prescribed antibiotics and the development of antibiotic resistance is addressed as well.