The two most clinically important members of the flavivirus genus, Zika virus (ZIKV) and dengue virus (DENV) pose a significant public health challenge. They cause a range of diseases in humans, from hemorrhagic to neurological manifestations, leading to economic and social burden worldwide. Nevertheless, there are no approved antiviral drugs to treat these infections. Zafirlukast is an orally available Food and Drug Administration (FDA) approved drug for the prophylaxis and treatment of chronic asthma. It is a leukotriene receptor antagonist (LTRA) with high selectivity of the cysteinyl leukotriene-1 receptor (CYSLTR1) that acts as immune modulator. Thus, we evaluated the antiviral potential of Zafirlukast against ZIKV and DENV in SK-N-SH cells. We showed that Zafirlukast exhibited potent antiviral activity against ZIKV, which could be linked to Zafirlukast’s immune blockade of TNF signaling pathways and its downstream signaling pathways such as MAPK and ERK1/2. In addition, our results showed that Zafirlukast also counteracts ZIKV-induced changes in key genes involved in cellular lipid metabolism. Thus, these findings highlight the translational potential of optimizing Zafirlukast as a therapeutic agent for the treatment of ZIKV and DENV.

Non-polio enteroviruses (NPEVs) are a known cause of neurological illnesses, and in recent years, respiratory complications have been linked to EV-D68, EV-A71, and human rhinovirus (HRV). Understanding and identifying the molecules responsible for the inflammatory responses associated with NPEVs is vital to targeting current therapeutic compounds effectively. One such molecule is HMGB1, which plays a critical role in inducing inflammation. Disulfide-HMGB1 interaction with TLR-4 leads to the release of pro-inflammatory cytokines. Infected or dying cells also secrete extracellular HMGB1 and innate immune molecules. The HMGB1-RAGE axis can trigger inflammasome formation by activating caspase-1, resulting in pyroptosis. Recent research has shown that EV-A71 infection induces gasdermin-D, which causes perforations in the plasma membrane and subsequent inflammasome formation and causes pyroptosis. This cascade releases IL-1β and IL-18, leading to cell lysis, inflammatory cell recruitment, and increased cytokine production. However, excessive production of these cells and cytokines can lead to severe complications, including cytokine storms that exacerbate disease symptoms. By focusing on these key molecular targets and pathways, we can move further to mitigate the devastating effects of uncontrolled inflammation during viral infections, including NPEVs. The therapeutic potential of compounds such as HMGB1 inhibitors, P2X7 receptor antagonists, and anti-inflammatory agents like ethyl pyruvate, heparin, glycyrrhizin, and resveratrol offers exciting avenues for future research and clinical application.

Every year, influenza virus infections cause significant morbidity and mortality worldwide. They pose a substantial burden of disease, not only in terms of health but also economic-wise. Owing to the ability of influenza viruses to continuously evolve, annual seasonal influenza vaccines are necessary as a prophylaxis. However, current influenza vaccines against seasonal strains have limited effectiveness and require yearly reformulation due to the virus undergoing antigenic drift or shift. Vaccine mismatches are common, conferring suboptimal protection against seasonal outbreaks, and the threat of the next pandemic continues to loom. Therefore, there is a great need to develop a universal influenza vaccine (UIV) capable of providing broad and durable protection against all influenza virus strains. In the quest to develop a UIV that would obviate the need for annual vaccination and formulation, a multitude of strategies are currently underway. Promising approaches include targeting the highly conserved epitopes of hemagglutinin (HA), neuraminidase (NA), M2 extracellular domain (M2e), and internal proteins of the influenza virus. The identification and characterisation of broadly neutralising antibodies (bnAbs) targeting conserved regions of the viral HA protein, in particular, have provided important insight into novel vaccine designs and platforms. This review discusses universal vaccine approaches presently under development, with an emphasis on those targeting the highly conserved stalk of the HA protein, recent technological advancements used, and the future prospects of a UIV in terms of its advantages, developmental obstacles and potential shortcomings.

Non-polio enterovirus such as EV-D68 and EV-A71 has been reported to cause a polio-like neurological disease known as acute flaccid myelitis. One of the diagnostics of acute flaccid myelitis is robust inflammation in cerebrospinal fluid. This may be due to the immune response triggered by EV-D68 and EV-A71 causing an influx of pro-inflammatory mediators to the infection site resulting in neurological disease. In order to reduce or prevent inflammation in the infection site, the mechanism and pathways of the immune response against EV-D68 and EV-A71 are important. Immune receptors are the sensor and the most important step to initiate the immune response. Pattern recognition receptors and inflammasome receptors are the main receptors to detect viruses including enterovirus. It is important to understand the mechanism and pathways receptors are involved.