Betacyanins from red pitahaya (Hylocereus polyrhizus) exhibit antiviral response against influenza A virus.

Seasonal influenza affects millions of lives worldwide, with the influenza A virus (IAV) responsible for pandemics and annual epidemics, causing the most severe illnesses resulting in patient hospitalizations or death. With IAV threatening the next global influenza pandemic, it is a race against time to search for antiviral drugs. Betacyanins are unique nitrogen-containing and water-soluble reddish-violet pigments that have been reported to possess antiviral properties against the dengue virus. This study aimed to examine the antiviral effect of betacyanins from red pitahaya (Hylocereus polyrhizus) on IAV-infected lung epithelial A549 cells. HPLC and LC-MS analysis of extracted betacyanin showed four betacyanins in the betacyanin fraction: phyllocactin, hylocerenin, betanin, and isobetanin. Cytotoxicity assay showed that betacyanin fractions were not cytotoxic to A549 cells at concentrations below 100 µg/mL. Betacyanin fraction concentrations of 12.5, 25.0, and 50.0 µg/mL prevented the formation of viral cytopathic effect and reduced virus titer in IAV-infected cells up to 72 h. A downregulation of protein and mRNA nucleoprotein expression levels was observed after treatment with 25.0 and 50.0 µg/mL of betacyanin fraction after 24 h, thereby providing evidence for the antiviral activity of betacyanin from red pitahaya against IAV in vitro.

Common spatial pattern for classification of loving kindness meditation EEG for single and multiple sessions.

While a very few studies have been conducted on classifying loving kindness meditation (LKM) and non-meditation electroencephalography (EEG) data for a single session, there are no such studies conducted for multiple session EEG data. Thus, this study aims at classifying existing raw EEG meditation data on single and multiple sessions to come up with meaningful inferences which will be highly beneficial when developing algorithms that can support meditation practices. In this analysis, data have been collected on Pre-Resting (before-meditation), Post-Resting (after-meditation), LKM-Self and LKM-Others for 32 participants and hence allowing us to conduct six pairwise comparisons for the four mind tasks. Common Spatial Patterns (CSP) is a feature extraction method widely used in motor imaginary brain computer interface (BCI), but not in meditation EEG data. Therefore, using CSP in extracting features from meditation EEG data and classifying meditation/non-meditation instances, particularly for multiple sessions will create a new path in future meditation EEG research. The classification was done using Linear Discriminant Analysis (LDA) where both meditation techniques (LKM-Self and LKM-Others) were compared with Pre-Resting and Post-Resting instances. The results show that for a single session of 32 participants, around 99.5% accuracy was obtained for classifying meditation/Pre-Resting instances. For the 15 participants when using five sessions of EEG data, around 83.6% accuracy was obtained for classifying meditation/Pre-Resting instances. The results demonstrate the ability to classify meditation/Pre-Resting data. Most importantly, this classification is possible for multiple session data as well. In addition to this, when comparing the classification accuracies of the six mind task pairs; LKM-Self, LKM-Others and Post-Resting produced relatively lower accuracies among them than the accuracies obtained for classifying Pre-Resting with the other three. This indicates that Pre-Resting has some features giving a better classification indicating that it is different from the other three mind tasks.

Evolution of SARS-CoV-2 Variants: Implications on Immune Escape, Vaccination, Therapeutic and Diagnostic Strategies.

The COVID-19 pandemic caused by SARS-CoV-2 is associated with a lower fatality rate than its SARS and MERS counterparts. However, the rapid evolution of SARS-CoV-2 has given rise to multiple variants with varying pathogenicity and transmissibility, such as the Delta and Omicron variants. Individuals with advanced age or underlying comorbidities, including hypertension, diabetes and cardiovascular diseases, are at a higher risk of increased disease severity. Hence, this has resulted in an urgent need for the development of better therapeutic and preventive approaches. This review describes the origin and evolution of human coronaviruses, particularly SARS-CoV-2 and its variants as well as sub-variants. Risk factors that contribute to disease severity and the implications of co-infections are also considered. In addition, various antiviral strategies against COVID-19, including novel and repurposed antiviral drugs targeting viral and host proteins, as well as immunotherapeutic strategies, are discussed. We critically evaluate strategies of current and emerging vaccines against SARS-CoV-2 and their efficacy, including immune evasion by new variants and sub-variants. The impact of SARS-CoV-2 evolution on COVID-19 diagnostic testing is also examined. Collectively, global research and public health authorities, along with all sectors of society, need to better prepare against upcoming variants and future coronavirus outbreaks.

Cannabis as antivirals.

Cannabis is a plant notorious for its psychoactive effect, but when used correctly, it provides a plethora of medicinal benefits. With more than 400 active compounds that have therapeutic properties, cannabis has been accepted widely as a medical treatment and for recreational purposes in several countries. The compounds exhibit various clinical benefits, which include, but are not limited to, anticancer, antimicrobial, and antioxidant properties. Among the vast range of compounds, multiple research papers have shown that cannabinoids, such as cannabidiol and delta-9-tetrahydrocannabinol, have antiviral effects. Recently, scientists found that both compounds can reduce severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral infection by downregulating ACE2 transcript levels and by exerting anti-inflammatory properties. These compounds also act as the SARS-CoV-2 main protease inhibitors that block viral replication. Apart from cannabinoids, terpenes in cannabis plants have also been widely explored for their antiviral properties. With particular emphasis on four different viruses, SARS-CoV-2, human immunodeficiency virus, hepatitis C virus, and herpes simplex virus-1, this review discussed the role of cannabis compounds in combating viral infections and the potential of both cannabinoids and terpenes as novel antiviral therapeutics.

Viral modulation of lipid rafts and their potential as putative antiviral targets.

Lipid rafts are ubiquitous in cells. They are identified as cholesterol and glycosphingolipid enriched microdomains on cellular membranes. They serve as platforms for cellular communications by functioning in signal transduction and membrane trafficking. Such structural organisation fulfils cellular needs for normal function, but at the same time increases vulnerability of cells to pathogen invasion. Viruses rely heavily on lipid rafts in basically every stage of the viral life cycle for successful infection. Various mechanisms of lipid rafts modification exploited by diverse viruses for attachment, internalisation, membrane fusion, genome replication, assembly and release have been brought to light. This review focuses on virus-raft interactions and how a wide range of viruses manipulate lipid rafts at distinct stages of infection. The importance of virus-raft interactions in viral infections has inspired researchers to discover and develop antivirals that target this interaction, such as statins, methyl-ß-cyclodextrin, viperin, 25-hydroxycholesterol and even anti-malarial drugs. The therapeutic modulations of lipid rafts as potential antiviral intervention from in vitro and in vivo evidence are discussed herein.

Alternative antiviral approaches to combat influenza A virus.

Influenza A (IAV) is a major human respiratory pathogen that contributes to a significant threat to health security, worldwide. Despite vaccinations and previous immunisations through infections, humans can still be infected with influenza several times throughout their lives. This phenomenon is attributed to the antigenic changes of hemagglutinin (HA) and neuraminidase (NA) proteins in IAV via genetic mutation and reassortment, conferring antigenic drift and antigenic shift, respectively. Numerous findings indicate that slow antigenic drift and reassortment-derived antigenic shift exhibited by IAV are key processes that allow IAVs to overcome the previously acquired host immunity, which eventually leads to the annual re-emergence of seasonal influenza and even pandemic influenza, in rare occasions. As a result, current therapeutic options hit a brick wall quickly. As IAV remains a constant threat for new outbreaks worldwide, the underlying processes of genetic changes and alternative antiviral approaches for IAV should be further explored to improve disease management. In the light of the above, this review discusses the characteristics and mechanisms of mutations and reassortments that contribute to IAV's evolution. We also discuss several alternative RNA-targeting antiviral approaches, namely the CRISPR/Cas13 systems, RNA interference (RNAi), and antisense oligonucleotides (ASO) as potential antiviral approaches against IAV.

Vision-Based Detection and Classification of Used Electronic Parts.

Economic and environmental sustainability is becoming increasingly important in today's world. Electronic waste (e-waste) is on the rise and options to reuse parts should be explored. Hence, this paper presents the development of vision-based methods for the detection and classification of used electronics parts. In particular, the problem of classifying commonly used and relatively expensive electronic project parts such as capacitors, potentiometers, and voltage regulator ICs is investigated. A multiple object workspace scenario with an overhead camera is investigated. A customized object detection algorithm determines regions of interest and extracts data for classification. Three classification methods are explored: (a) shallow neural networks (SNNs), (b) support vector machines (SVMs), and (c) deep learning with convolutional neural networks (CNNs). All three methods utilize 30 × 30-pixel grayscale image inputs. Shallow neural networks achieved the lowest overall accuracy of 85.6%. The SVM implementation produced its best results using a cubic kernel and principal component analysis (PCA) with 20 features. An overall accuracy of 95.2% was achieved with this setting. The deep learning CNN model has three convolution layers, two pooling layers, one fully connected layer, softmax, and a classification layer. The convolution layer filter size was set to four and adjusting the number of filters produced little variation in accuracy. An overall accuracy of 98.1% was achieved with the CNN model.

SARS-CoV-2 Non-Structural Proteins and Their Roles in Host Immune Evasion.

Coronavirus disease 2019 (COVID-19) has caused an unprecedented global crisis and continues to threaten public health. The etiological agent of this devastating pandemic outbreak is the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). COVID-19 is characterized by delayed immune responses, followed by exaggerated inflammatory responses. It is well-established that the interferon (IFN) and JAK/STAT signaling pathways constitute the first line of defense against viral and bacterial infections. To achieve viral replication, numerous viruses are able to antagonize or hijack these signaling pathways to attain productive infection, including SARS-CoV-2. Multiple studies document the roles of several non-structural proteins (NSPs) of SARS-CoV-2 that facilitate the establishment of viral replication in host cells via immune escape. In this review, we summarize and highlight the functions and characteristics of SARS-CoV-2 NSPs that confer host immune evasion. The molecular mechanisms mediating immune evasion and the related potential therapeutic strategies for controlling the COVID-19 pandemic are also discussed.

Repurposing Molnupiravir for COVID-19: The Mechanisms of Antiviral Activity.

Molnupiravir is a ß-d-N4-hydroxycytidine-5'-isopropyl ester (NHC) compound that exerts antiviral activity against various RNA viruses such as influenza, SARS, and Ebola viruses. Thus, the repurposing of Molnupiravir has gained significant attention for combatting infection with SARS-CoV-2, the etiological agent of COVID-19. Recently, Molnupiravir was granted authorization for the treatment of mild-to-moderate COVID-19 in adults. Findings from in vitro experiments, in vivo studies and clinical trials reveal that Molnupiravir is effective against SARS-CoV-2 by inducing viral RNA mutagenesis, thereby giving rise to mutated complementary RNA strands that generate non-functional viruses. To date, the data collectively suggest that Molnupiravir possesses promising antiviral activity as well as favorable prophylactic efficacy, attributed to its effective mutagenic property of disrupting viral replication. This review discusses the mechanisms of action of Molnupiravir and highlights its clinical utility by disabling SARS-CoV-2 replication, thereby ameliorating COVID-19 severity. Despite relatively few short-term adverse effects thus far, further detailed clinical studies and long-term pharmacovigilance are needed in view of its mutagenic effects.

Heterogeneous Ribonucleoprotein A1 (hnRNPA1) Interacts with the Nucleoprotein of the Influenza a Virus and Impedes Virus Replication.

Influenza A virus (IAV), like other viruses, depends on the host cellular machinery for replication and production of progeny. The relationship between a virus and a host is complex, shaped by many spatial and temporal interactions between viral and host proteome, ultimately dictating disease outcome. Therefore, it is imperative to identify host-virus interactions as crucial determinants of disease pathogenies. Heterogeneous ribonucleoprotein A1 (hnRNPA1) is an RNA binding protein involved in the life cycle of many DNA and RNA viruses; however, its role in IAV remains undiscovered. Here we report that human hnRNPA1 physically interacts with the nucleoprotein (NP) of IAV in mammalian cells at different time points of the viral replication cycle. Temporal distribution studies identify hnRNPA1 and NP co-localize in the same cellular milieu in both nucleus and mitochondria in NP-transfected and IAV-infected mammalian cells. Interestingly, hnRNPA1 influenced NP gene expression and affected viral replication. Most importantly, hnRNPA1 knockdown caused a significant increase in NP expression and enhanced viral replication (93.82%) in IAV infected A549 cells. Conversely, hnRNPA1 overexpression reduced NP expression at the mRNA and protein levels and impeded virus replication by (60.70%), suggesting antagonistic function. Taken together, results from this study demonstrate that cellular hnRNPA1 plays a protective role in the host hitherto unknown and may hold potential as an antiviral target to develop host-based therapeutics against IAV.

The gut virome in two indigenous populations from Malaysia.

The human gut contains a complex microbiota dominated by bacteriophages but also containing other viruses and bacteria and fungi. There are a growing number of techniques for the extraction, sequencing, and analysis of the virome but currently no standardized protocols. This study established an effective workflow for virome analysis to investigate the virome of stool samples from two understudied ethnic groups from Malaysia: the Jakun and Jehai Orang Asli. By using the virome extraction and analysis workflow with the Oxford Nanopore Technology, long-read sequencing successfully captured close to full-length viral genomes. The virome composition of the two indigenous Malaysian communities were remarkably different from those found in other parts of the world. Additionally, plant viruses found in the viromes of these individuals were attributed to traditional food-seeking methods. This study establishes a human gut virome workflow and extends insights into the healthy human gut virome, laying the groundwork for comparative studies.

Repositioning Ivermectin for Covid-19 treatment: Molecular mechanisms of action against SARS-CoV-2 replication.

Ivermectin (IVM) is an FDA approved macrocyclic lactone compound traditionally used to treat parasitic infestations and has shown to have antiviral potential from previous in-vitro studies. Currently, IVM is commercially available as a veterinary drug but have also been applied in humans to treat onchocerciasis (river blindness - a parasitic worm infection) and strongyloidiasis (a roundworm/nematode infection). In light of the recent pandemic, the repurposing of IVM to combat SARS-CoV-2 has acquired significant attention. Recently, IVM has been proven effective in numerous in-silico and molecular biology experiments against the infection in mammalian cells and human cohort studies. One promising study had reported a marked reduction of 93% of released virion and 99.98% unreleased virion levels upon administration of IVM to Vero-hSLAM cells. IVM's mode of action centres around the inhibition of the cytoplasmic-nuclear shuttling of viral proteins by disrupting the Importin heterodimer complex (IMPα/ß1) and downregulating STAT3, thereby effectively reducing the cytokine storm. Furthermore, the ability of IVM to block the active sites of viral 3CLpro and S protein, disrupts important machinery such as viral replication and attachment. This review compiles all the molecular evidence to date, in review of the antiviral characteristics exhibited by IVM. Thereafter, we discuss IVM's mechanism and highlight the clinical advantages that could potentially contribute towards disabling the viral replication of SARS-CoV-2. In summary, the collective review of recent efforts suggests that IVM has a prophylactic effect and would be a strong candidate for clinical trials to treat SARS-CoV-2.

The Suppressor of Cytokine Signalling family of proteins and their potential impact on COVID-19 disease progression.

The family of Suppressor of Cytokine Signalling (SOCS) proteins plays pivotal roles in cytokine and immune regulation. Despite their key roles, little attention has been given to the SOCS family as compared to other feedback regulators. To date, SOCS proteins have been found to be exploited by viruses such as herpes simplex virus (HSV), hepatitis B virus (HBV), hepatitis C virus (HCV), Zika virus, respiratory syncytial virus (RSV), Ebola virus, influenza A virus (IAV) and SARS-CoV, just to name a few. The hijacking and subsequent upregulation of the SOCS proteins upon viral infection, suppress the associated JAK-STAT signalling activities, thereby reducing the host antiviral response and promoting viral replication. Two SOCS protein family members, SOCS1 and SOCS3 are well-studied and their roles in the JAK-STAT signalling pathway are defined as attenuating interferon (IFN) signalling upon viral infection. The upregulation of SOCS protein by SARS-CoV during the early stages of infection implies strong similarity with SARS-CoV-2, given their closely related genomic organisation. Thus, this review aims to outline the plausibility of SOCS protein inhibitors as a potential therapeutic regimen for COVID-19 patients. We also discuss the antagonists against SOCS protein to offer an overview on the previous 'successes' of SOCS protein inhibition in various viral infections that may portray possible clues for COVID-19 disease management.

Current vaccine approaches and emerging strategies against herpes simplex virus (HSV).

Introduction: Vaccine development for the disease caused by the herpes simplex virus (HSV) has been challenging over the years and is always in dire need of novel approaches for prevention and cure. To date, the HSV disease remains incurable and challenging to prevent. The disease is extremely widespread due to its high infection rate, resulting in millions of infection cases worldwide.Areas covered: This review first explains the diverse forms of HSV-related disease presentations and reports past vaccine history for the disease. Next, this review examines current and novel HSV vaccine approaches being studied and tested for efficacy and safety as well as vaccines in clinical trial phases I to III. Modern approaches to vaccine design using bioinformatics are described. Finally, we discuss measures to enhance new vaccine development pipelines for HSV.Expert opinion: Modernized approaches using in silico analysis and bioinformatics are emerging methods that exhibit potential for producing vaccines with enhanced targets and formulations. Although not yet fully established for HSV disease, we describe current studies using these approaches for HSV vaccine design to shed light on these methods. In addition, we provide up-to-date requirements of immunogenicity, adjuvant selection, and routes of administration.

Comparative Transcriptomic and Molecular Pathway Analyses of HL-CZ Human Pro-Monocytic Cells Expressing SARS-CoV-2 Spike S1, S2, NP, NSP15 and NSP16 Genes.

The ongoing COVID-19 pandemic is a clear and present threat to global public health. Research into how the causative SARS-CoV-2 virus together with its individual constituent genes and proteins interact with target host cells can facilitate the development of improved strategies to manage the acute and long-term complications of COVID-19. In this study, to better understand the biological roles of critical SARS-CoV-2 proteins, we determined and compared the host transcriptomic responses of the HL-CZ human pro-monocytic cell line upon transfection with key viral genes encoding the spike S1 subunit, S2 subunit, nucleocapsid protein (NP), NSP15 (endoribonuclease), and NSP16 (2'-O-ribose-methyltransferase). RNA sequencing followed by gene set enrichment analysis and other bioinformatics tools revealed that host genes associated with topologically incorrect protein, virus receptor activity, heat shock protein binding, endoplasmic reticulum stress, antigen processing and presentation were up-regulated in the presence of viral spike S1 expression. With spike S2 expression, pro-monocytic genes associated with the interferon-gamma-mediated signaling pathway, regulation of phosphatidylinositol 3-kinase activity, adipocytokine signaling pathway, and insulin signaling pathway were down-regulated, whereas those associated with cytokine-mediated signaling were up-regulated. The expression of NSP15 induced the up-regulation of genes associated with neutrophil degranulation, neutrophil-mediated immunity, oxidative phosphorylation, prion disease, and pathways of neurodegeneration. The expression of NSP16 resulted in the down-regulation of genes associated with S-adenosylmethionine-dependent methyltransferase activity. The expression of NP down-regulated genes associated with positive regulation of neurogenesis, nervous system development, and heart development. Taken together, the complex transcriptomic alterations arising from these viral-host gene interactions offer useful insights into host genes and their pathways that potentially contribute to SARS-CoV-2 pathogenesis.

SARS coronavirus outbreaks past and present-a comparative analysis of SARS-CoV-2 and its predecessors.

The Coronavirus Disease 2019 (COVID-19), a pneumonic disease caused by the SARS Coronavirus 2 (SARS-CoV-2), is the 7th Coronavirus to have successfully infected and caused an outbreak in humans. Genome comparisons have shown that previous isolates, the SARS-related coronavirus (SARSr-CoV), including the SARS-CoV are closely related, yet different in disease manifestation. Several explanations were suggested for the undetermined origin of SARS-CoV-2, in particular, bats, avian and Malayan pangolins as reservoir hosts, owing to the high genetic similarity. The general morphology and structure of all these viral isolates overlap with analogous disease symptoms such as fever, dry cough, fatigue, dyspnoea and headache, very similar to the current SARS-CoV-2. Chest CT scans for SARS-CoV-2, SARS-CoV and MERS-CoV reveal pulmonary lesions, bilateral ground-glass opacities, and segmental consolidation in the lungs, a common pathological trait. With greatly overlapping similarities among the previous coronavirus, the SARS-CoV, it becomes interesting to observe marked differences in disease severity of the SARS-CoV-2 thereby imparting it the ability to rapidly transmit, exhibit greater stability, bypass innate host defences, and increasingly adapt to their new host thereby resulting in the current pandemic. The most recent B.1.1.7, B.1.351 and P.1 variants of SARS-CoV-2, highlight the fact that changes in amino acids in the Spike protein can contribute to enhanced infection and transmission efficiency. This review covers a comparative analysis of previous coronavirus outbreaks and highlights the differences and similarities among different coronaviruses, including the most recent isolates that have evolved to become easily transmissible with higher replication efficiency in humans.

A Comprehensive Review on Critical Issues and Possible Solutions of Motor Imagery Based Electroencephalography Brain-Computer Interface.

Motor imagery (MI) based brain-computer interface (BCI) aims to provide a means of communication through the utilization of neural activity generated due to kinesthetic imagination of limbs. Every year, a significant number of publications that are related to new improvements, challenges, and breakthrough in MI-BCI are made. This paper provides a comprehensive review of the electroencephalogram (EEG) based MI-BCI system. It describes the current state of the art in different stages of the MI-BCI (data acquisition, MI training, preprocessing, feature extraction, channel and feature selection, and classification) pipeline. Although MI-BCI research has been going for many years, this technology is mostly confined to controlled lab environments. We discuss recent developments and critical algorithmic issues in MI-based BCI for commercial deployment.

The Immunomodulatory CEA Cell Adhesion Molecule 6 (CEACAM6/CD66c) Is a Protein Receptor for the Influenza a Virus.

To establish a productive infection in host cells, viruses often use one or multiple host membrane glycoproteins as their receptors. For Influenza A virus (IAV) such a glycoprotein receptor has not been described, to date. Here we show that IAV is using the host membrane glycoprotein CD66c as a receptor for entry into human epithelial lung cells. Neuraminidase (NA), a viral spike protein, binds to CD66c on the cell surface during IAV entry into the host cells. Lung cells overexpressing CD66c showed an increase in virus binding and subsequent entry into the cell. Upon comparison, CD66c demonstrated higher binding capacity than other membrane glycoproteins (EGFR and DC-SIGN) reported earlier to facilitate IAV entry into host cells. siRNA mediated knockdown of CD66c from lung cells inhibited virus binding on cell surface and entry into cells. Blocking CD66c by antibody on the cell surface resulted in decreased virus entry. We found that CD66c is a specific glycoprotein receptor for influenza A virus that did not affect entry of non-IAV RNA virus (Hepatitis C virus). Finally, IAV pre-incubated with recombinant CD66c protein when administered intranasally in mice showed decreased cytopathic effects in mice lungs. This publication is the first to report CD66c (Carcinoembryonic cell adhesion molecule 6 or CEACAM6) as a glycoprotein receptor for Influenza A virus.

COVID-19: A Review on the Novel Coronavirus Disease Evolution, Transmission, Detection, Control and Prevention.

Three major outbreaks of the coronavirus, a zoonotic virus known to cause respiratory disease, have been reported since 2002, including SARS-CoV, MERS-CoV and the most recent 2019-nCoV, or more recently known as SARS-CoV-2. Bats are known to be the primary animal reservoir for coronaviruses. However, in the past few decades, the virus has been able to mutate and adapt to infect humans, resulting in an animal-to-human species barrier jump. The emergence of a novel coronavirus poses a serious global public health threat and possibly carries the potential of causing a major pandemic outbreak in the naïve human population. The recent outbreak of COVID-19, the disease caused by SARS-CoV-2, in Wuhan, Hubei Province, China has infected over 36.5 million individuals and claimed over one million lives worldwide, as of 8 October 2020. The novel virus is rapidly spreading across China and has been transmitted to 213 other countries/territories across the globe. Researchers have reported that the virus is constantly evolving and spreading through asymptomatic carriers, further suggesting a high global health threat. To this end, current up-to-date information on the coronavirus evolution and SARS-CoV-2 modes of transmission, detection techniques and current control and prevention strategies are summarized in this review.