Coxsackievirus A6 (CVA6) was identified as an important cause of "severe" hand, foot, and mouth disease (HFMD) during the 2011–2012 outbreak in North America. The atypical cutaneous features in this outbreak have not been well documented.

The cutaneous manifestations of CVA6-associated HFMD may be more extensive and variable than classic HFMD. Four distinct morphologies characterize this exanthem: (1) widespread vesiculobullous and erosive lesions, (2) "eczema coxsackium," (3) an eruption similar to Gianotti-Crosti, and (4) purpuric lesions. (Read the full article)

Respiratory syncytial virus (RSV) infection is a leading cause of hospitalization among infants. Most estimates of RSV hospitalization rates are imprecise, having been calculated by using retrospective discharge diagnosis data and stratified age groups no narrower than 6 to 12 months.

Prospective, population-based surveillance data for infants hospitalized with laboratory-confirmed RSV infection were combined with birth certificate information to yield more precise age-specific hospitalization rates. These data should help determine priorities for the use of existing and future RSV prophylaxis strategies. (Read the full article)

Preterm and low birth weight infants are at increased risk of hospitalization due to rotavirus gastroenteritis, and rotavirus vaccine is immunogenic and well tolerated among these infants when provided at or after discharge from the NICU.

Many preterm infants with a birth weight of ≤1500 g are not eligible to receive rotavirus vaccination because they remain in the NICU beyond the upper age limit recommended for immunization. New strategies are needed. (Read the full article)

Human rhinovirus has been known as the common cold agent. Recently, studies have reported that this virus is responsible for severe infections of the lower respiratory tract in children. Reports of factors that increase disease severity have been contradictory.

This study identifies some of the factors involved in disease severity in HRV infections in children. We expect that children at risk for developing severe disease could be identified sooner and appropriate measures could be taken. (Read the full article)

Quantitative real-time polymerase chain reaction allows sensitive detection of respiratory viruses. The clinical significance of detection of specific viruses is not fully understood, however, and several viruses have been detected in the respiratory tract of asymptomatic children.

Our results indicate that quantitative real-time polymerase chain reaction is limited at distinguishing acute infection from detection in asymptomatic children for rhinovirus, bocavirus, adenovirus, enterovirus, and coronavirus. (Read the full article)

Down syndrome is an independent risk factor for severe respiratory syncytial virus infection and subsequent hospitalization.

This observational study suggests that immunoprophylaxis may reduce respiratory syncytial virus-related hospitalization by 3.6-fold (95% confidence interval, 1.5–8.7) in children with Down syndrome overall. (Read the full article)

Rotavirus vaccination is discouraged during hospitalization, given concerns regarding live-attenuated virus transmission; vaccination is recommended upon NICU discharge for eligible infants, however. Vaccination must be initiated before 104 days of age or infants become age-ineligible.

RotaTeq vaccine administered with routine 2-month vaccinations within the NICU was tolerated in recipients, with no suggestion of symptomatic nosocomial transmission to neighboring unvaccinated infants. (Read the full article)

Since the introduction of rotavirus vaccines, diarrhea-associated health care utilization among US children has decreased substantially. Moreover, indirect benefits from rotavirus vaccination have been observed in unvaccinated children and in adults.

With increasing rotavirus vaccine coverage during 2009–2011, we observed continued reductions in diarrhea-associated health care utilization and cost. Both rotavirus vaccines conferred high protection against rotavirus hospitalizations; pentavalent rotavirus vaccine provided durable protection through the fourth year of life. (Read the full article)

The short-term immunogenicity and safety of a HPV4 vaccine have been previously evaluated in preadolescents and adolescents. To date, no long-term studies of the safety, effectiveness, and immunogenicity of the HPV4 vaccine have been reported in this age group.

The HPV4 vaccine administered to adolescents demonstrated durability in clinically effective protection and sustained antibody titers over 8 years. These data, along with extensive postapproval safety surveillance data, should help reinforce national recommendations for HPV vaccination of preadolescents and adolescents. (Read the full article)

Rhinoviruses are commonly detected in both acutely ill and asymptomatic infants and children. The finding may represent new infection or prolonged presence of rhinovirus RNA in the respiratory tract.

In young, otherwise healthy infants, shedding of RNA from the same rhinovirus strain rarely persisted longer than 30 days. (Read the full article)

Respiratory syncytial virus (RSV) infection is a common cause of pediatric hospitalizations. Mortality rates associated with RSV hospitalizations are based on estimates from studies conducted decades ago. Accurate understanding of mortality is required for identifying high-risk infants and children.

Mortality associated with RSV is uncommon in the 21st century, with annual deaths far lower than previous estimates. The majority of deaths occurred in infants with complex chronic conditions or in those with life-threatening conditions in addition to RSV infection. (Read the full article)

Uptake of rotavirus vaccines has increased steadily since introduction. Despite their demonstrated impact, rotavirus vaccine coverage is lower than for other vaccines recommended in infancy and disease continues to occur.

We observed higher rotavirus detection rates among patients from provider locations with lower rotavirus vaccine coverage; providers who do not offer rotavirus vaccine to age-eligible children may create pockets of susceptible children that serve as reservoirs of ongoing disease transmission. (Read the full article)

Myxovirus resistance protein A (MxA) is a protein induced during viral infections. A few small-scale studies have suggested that MxA could be used as a marker of viral infection in clinical routine practice.

This study involves the largest patient population thus far and confirms the usefulness of MxA for diagnosing viral infections in children consulting the emergency department in a clinical routine setting. (Read the full article)

Clinical trials of the quadrivalent human papillomavirus vaccine show it to be highly efficacious in preventing vaccine-type–specific cervical dysplasia and anogenital warts, but few studies have assessed its effects in the real world and none have done so at the program/population level.

This study provides strong evidence of the early benefits of quadrivalent human papillomavirus vaccination on reductions in cervical dysplasia and possible reductions in anogenital warts among girls aged 14 to 17 years, offering additional justification for not delaying vaccination until girls are older. (Read the full article)

Previous studies have shown that concomitant administration of the quadrivalent human papillomavirus vaccine with MCV4 and Tdap was generally well tolerated and did not interfere with the immune responses to the respective vaccines.

Concomitant administration of the novel 9-valent human papillomavirus vaccine with MCV4 and Tdap, 2 vaccines that are currently recommended for routine vaccination of adolescents, did not compromise the safety, tolerability, and immunogenicity of the individual vaccines. (Read the full article)

Making a diagnosis of Kawasaki disease (KD) is often a diagnostic dilemma. This dilemma is confounded when children present with symptoms consistent with known, common respiratory viruses and/or with KD symptoms that could potentially be attributed to a respiratory virus.

Patients with KD commonly have a concurrent respiratory viral infection. Clinicians should not dismiss the diagnosis of KD based on the presence of respiratory symptoms. Furthermore, a positive respiratory virus test result should not be used to exclude the diagnosis of KD. (Read the full article)

Congenital cytomegalovirus infection is the leading infectious cause of neurologic disabilities and sensorineural hearing loss in children. Little is known concerning the frequency and impact of vestibular disorders induced by cytomegalovirus infection.

This study reports on the largest cohort of vestibular assessment of children congenitally infected with cytomegalovirus, demonstrating vestibular damages, and analyzes the correlations between vestibular dysfunction and hearing impairment or severity of infection. Cytomegalovirus infection affects postural development in children. (Read the full article)

Minister of Finance Tito Mboweni has announced a number of "exceptional tax measures as part of the fiscal package outlined by President Cyril Ramaphosa to fight the coronavirus pandemic.

If you contracted the coronavirus at work, you may be able to claim for temporary or permanent disability, depending on how you were affected - but you will have to prove that you did, in fact, become ill at work.

The developer, Ndemic Creations, wants to remind people that Plague Inc. is just a game, not a scientific model. The game's popularity has skyrocketed amid the ongoing coronavirus outbreak, which has managed to spread to the US.

Very carefully, experts say, while understanding that federal laws governing special education were not written with online education in mind.

Track where schools are closed and their status for reopening.

Professor of Chemistry Paul Cremer is developing a biosensor platform that could be used to perform real-time, continuous detection of SARS-CoV-2, the virus that causes COVID-19.

To help ease the transition to remote instruction, educators have launched virtual professional learning communities to share resources, ask questions, and give advice.

Allon Raiz is CEO of business incubator Raizcorp. In this series of articles, he offers entrepreneurs advice on surviving a crisis.

Stokvels are an important strategy for financial survival, so it's crucial to find a way to make them work during the pandemic, says Dr Norman Chivasa.

Now, more than ever, we need to be listening for market signals and ensuring that our businesses are primed to both take advantage of opportunities and to mitigate risks, says Allon Raiz.

Authorities unable or unwilling to face up to a reality that might reveal their own shortcomings and ineptitude, usually resort to pinpointing a scapegoat. This year, Covid-19 fits that bill, says Terry Bell.

As editor Wilhelm Crous puts it, "We haven't seen this movie before."

Read an extract from business author and coach Douglas Kruger's latest book, Virus-proof your small business.

Strategic partnerships could be used to create win-win outcomes, says Sifiso Skenjana.

To history buffs, the Covid-19 pandemic must seem eerily familiar, says Noah Smith.

Argentina is a case study in what happens when an economy already on its knees implements an aggressive lockdown, says Mac Margolis.

Background: This study summarizes drug resistance analyses in 4 recent phase 2b trials of the respiratory syncytial virus (RSV) fusion inhibitor presatovir in naturally infected adults.

Methods: Adult hematopoietic cell transplant (HCT) recipients, lung transplant recipients, or hospitalized patients with naturally acquired, laboratory-confirmed RSV infection were enrolled in 4 randomized, double-blind, placebo-controlled studies with study-specific presatovir dosing. Full-length RSV F sequences amplified from nasal swabs obtained at baseline and postbaseline were analyzed by population sequencing. Substitutions at RSV fusion inhibitor resistance-associated positions are reported.

Results: Genotypic analyses were performed on 233 presatovir-treated and 149 placebo-treated subjects. RSV F variant V127A was present in 8 subjects at baseline. Population sequencing detected treatment-emergent substitutions in 10/89 (11.2%) HCT recipients with upper and 6/29 (20.7%) with lower respiratory tract infection, 1/35 (2.9%) lung transplant recipients, and 1/80 (1.3%) hospitalized patients treated with presatovir; placebo-treated subjects had no emergent resistance-associated substitutions. Subjects with substitutions at resistance-associated positions had smaller decreases in viral load during treatment relative to those without, but similar clinical outcomes.

Conclusions: Subject population type and dosing regimen may have influenced RSV resistance development during presatovir treatment. Subjects with vs without genotypic resistance development had decreased virologic responses but comparable clinical outcomes.

The quinoline MK-571 is the most commonly used inhibitor of multidrug resistance protein-1 (MRP-1) but was originally developed as a cysteinyl leukotriene receptor 1 (CysLTR1) antagonist. While studying the modulatory effect of MRP-1 on anti-hepatitis C virus (HCV) direct acting-antivirals (DAA) efficiency, we observed an unexpected anti-HCV effect of compound MK-571 alone. This anti-HCV activity was characterized in Huh7.5 cells stably harboring a subgenomic genotype 1b replicon. A dose-dependent decrease of HCV RNA levels was observed upon MK-571 administration, with an EC₅₀ of 9±0.3 μM and a maximum HCV RNA level reduction of approximatively 1 Log₁₀. MK-571 also reduced the replication of the HCV full-length J6/JFH1 model in a dose-dependent manner. However, probenecid and apigenin homodimer (APN), two specific inhibitors of MRP-1, had no effect on HCV replication. In contrast, the CysLTR1 antagonists SR2640 increased HCV-SGR RNA levels in a dose-dependent manner, with a maximum increase of 10-fold. In addition, a combination of natural CysLTR1 agonist (LTD4) or antagonists (zafirlukast, cinalukast, and SR2640) with MK-571 completely reversed its antiviral effect, suggesting its anti-HCV activity is related to CysLTR1 rather to MRP-1 inhibition. In conclusion, we showed that MK-571 inhibits HCV replication in hepatoma cell cultures by acting as a CysLTR1 receptor antagonist, thus unraveling a new host-virus interaction in the HCV life cycle.

Bunyaviruses are significant human pathogens, causing diseases ranging from hemorrhagic fevers to encephalitis. Among these viruses, La Crosse virus (LACV), a member of the California serogroup, circulates in the eastern and midwestern United States. While LACV infection is often asymptomatic, dozens of cases of encephalitis are reported yearly. Unfortunately, no antivirals have been approved to treat LACV infection. Here, we developed a method to rapidly test potential antivirals against LACV infection. From this screen, we identified several potential antiviral molecules, including known antivirals. Additionally, we identified many novel antivirals that exhibited antiviral activity without affecting cellular viability. Valinomycin, a potassium ionophore, was among our top targets. We found that valinomycin exhibited potent anti-LACV activity in multiple cell types in a dose-dependent manner. Valinomycin did not affect particle stability or infectivity, suggesting that it may preclude virus replication by altering cellular potassium ions, a known determinant of LACV entry. We extended these results to other ionophores and found that the antiviral activity of valinomycin extended to other viral families including bunyaviruses (Rift Valley fever virus, Keystone virus), enteroviruses (Coxsackievirus, rhinovirus), flavirivuses (Zika), and coronaviruses (HCoV-229E and MERS-CoV). In all viral infections, we observed significant reductions in virus titer in valinomycin-treated cells. In sum, we demonstrate the importance of potassium ions to virus infection, suggesting a potential therapeutic target to disrupt virus replication.

Importance No antivirals are approved for the treatment of bunyavirus infection. The ability to rapidly screen compounds and identify novel antivirals is one means to accelerate drug discovery for viruses with no approved treatments. We used this approach to screen hundreds of compounds against La Crosse virus, an emerging bunyavirus that causes significant disease, including encephalitis. We identified several known and previously unidentified antivirals. We focused on a potassium ionophore, valinomycin, due to its promising in vitro antiviral activity. We demonstrate that valinomycin, as well as a selection of other ionophores, exhibits activity against La Crosse virus as well as several other distantly related bunyaviruses. We finally observe that valinomycin has activity against a wide array of human viral pathogens, suggesting that disrupting potassium ion homeostasis with valinomycin may be a potent host pathway to target to quell virus infection.

Attention has been paid to H5N6 highly pathogenic avian influenza virus (HPAIV) because of its heavy burden on the poultry industry and human mortality. Since an influenza A virus carrying N6 neuraminidase (NA) has never spread in humans, the potential for H5N6 HPAIV to cause disease in humans and the efficacy of antiviral drugs against the virus need to be urgently assessed. We used non-human primates to elucidate the pathogenesis of H5N6 HPAIV as well as to determine the efficacy of antiviral drugs against the virus. H5N6 HPAIV infection led to high fever in cynomolgus macaques. The lung injury caused by the virus was severe with diffuse alveolar damage and neutrophil infiltration. In addition, an increase in IFN-α showed an inverse correlation with virus titers during the infection process. Oseltamivir was effective for reducing H5N6 HPAIV propagation, and continuous treatment with peramivir reduced virus propagation and severity of symptoms in the early stage. This study also showed the pathologically severe lung injury states in the cynomolgus macaques infected with H5N6 HPAIV, even in those that received early antiviral drug treatments, indicating the need for close monitoring and the need for further studies on the virus pathogenicity and new antiviral therapies.

Despite the worldwide re-emergence of the chikungunya virus (CHIKV) and the high morbidity associated with CHIKV infections, there is no approved vaccine or antiviral treatment available. We here aim to identify the target of a novel class of CHIKV inhibitors i.e. CHVB series. CHVB compounds inhibit the in vitro replication of CHIKV isolates with 50% effective concentrations in the low micromolar range. A CHVB-resistant variant (CHVB^res) was selected that carried two mutations in the gene encoding nsP1 (responsible for viral RNA capping), one mutation in nsP2 and one mutation in nsP3. Reverse genetics studies demonstrated that both nsP1 mutations were necessary and sufficient to achieve ~18-fold resistance, suggesting that CHVB targets viral mRNA capping. Interestingly, CHVB^res was cross-resistant to the previously described CHIKV capping inhibitors from the MADTP series, suggesting they share a similar mechanism of action. In enzymatic assays, CHVB inhibited the methyltransferase and guanylyltransferase activities of alphavirus nsP1 proteins. To conclude, we identified a class of CHIKV inhibitors that targets the viral capping machinery. The potent anti-CHIKV activity makes this chemical scaffold a potential candidate for CHIKV drug development.

Ebola Virus (EBOV) is among the most devastating pathogens causing fatal hemorrhagic fever in humans. The 2013–2016 epidemics resulted in over 11000 deaths, while another outbreak is currently ongoing. Since there is no FDA-approved drug so far to fight EBOV infection, there is an urgent need to focus on drug discovery. Considering the tight correlation between the high EBOV virulence and its ability to suppress the type-I Interferon (IFN-I) system, identifying molecules targeting viral protein VP24, one of the main virulence determinants blocking IFN response, is a promising novel anti-EBOV therapy approach. Hence, in the effort of finding novel EBOV inhibitors, a screening of a small set of flavonoids was performed, showing that Quercetin and Wogonin can suppress the VP24 effect on IFN-I signaling inhibition. The mechanism of action of the most active compound, Quercetin, showing an IC₅₀ value of 7.4 μM, was characterized to significantly restore the IFN-I signaling cascade, blocked by VP24, by directly interfering with the VP24 binding to karyopherin-α and thus restoring P-STAT1 nuclear transport and IFN genes transcription. Quercetin significantly blocked viral infection, specifically targeting EBOV VP24 anti-IFN-I function. Overall, Quercetin is the first identified inhibitor of the EBOV VP24 anti-IFN function, representing a molecule interacting with a viral binding site that is very promising for further drug development aiming to block EBOV infection at the early steps.

Avast is harvesting users' browser histories on the pretext that the data has been 'de-identified,' thus protecting your privacy. But the data, which is being sold to third parties, can be linked back to people's real identities, exposing every click and search they've made.

The hackers have been using files and emails that warn about a new coronavirus strain to trick users into opening them. Doing so can secretly deliver malware to the victim's machine.

Windows Defender is improving, but you still shouldn't rely on Windows 10's security tools as your sole means of protection. Many free third-party security apps are more effective at keeping you safe. We've tested 17 no-cost services to help you find the best free antivirus for protecting your PC.

Equity markets have rallied Monday as countries eased coronavirus lockdown measures, but oil prices tumbled as a supply glut offset output cuts.

The surge in stocks was on the back of positive news from trials being conducted on a potential treatment for the coronavirus. With most economies looking to partially reopen their economies, this brought a jump across most asset classes including commodities.

Swiss refiner Valcambi SA tried for five straight days last month to move a shipment of gold out of Hong Kong. Twice the metal was packed carefully onto a plane, only to be offloaded again.

Funders have been both fast and thoughtful about how to work with national and local partners to listen to needs from the field, identify best practices, and deploy resources quickly, says Celine Coggins.

"This pandemic has given us an opportunity to think boldly about students' educational needs and how to creatively respond to them," says Katherine Haley.

"Folks in some foundations are quietly expressing frustration that they've been cautioned to stay in their lane and only fund things aligned with their pre-COVID strategy," says Stacey Childress.

In an effort to help mitigate the disruptive effects of the deadly COVID-19 virus, an interdisciplinary team of Penn State researchers are developing a novel methodology to analyze its spread and the impacts on policy to create better-prepared and more-resilient health care systems.