Viral interstitial pneumonia is rarely associated with rhabdomyolysis-induced acute kidney injury (AKI) and evolving systemic lupus erythematosus (SLE) with no lupus flare. Here, we report an adult male with human rhinovirus-associated viral pneumonia and rhabdomyolysis-related AKI requiring dialysis. He was detected to be anti-nuclear, anti-Smith, and anti-U1 ribonucleoprotein antibodies positive. His kidney biopsy revealed normal glomeruli, with immunofluorescence showing a full-house pattern. Renal function and lung function gradually improved to normal without any immunosuppressants.

Respiratory viral infections (VRTIs) rank among the leading causes of global morbidity and mortality, affecting millions of individuals each year across all age groups. These infections are caused by various pathogens, including rhinoviruses (RVs), adenoviruses (AdVs), and coronaviruses (CoVs), which are particularly prevalent during colder seasons. Although many VRTIs are self-limiting, their frequent recurrence and potential for severe health complications highlight the critical need for effective therapeutic strategies. Viral proteases are crucial for the maturation and replication of viruses, making them promising therapeutic targets. This review explores the pivotal role of viral proteases in the lifecycle of respiratory viruses and the development of protease inhibitors as a strategic response to these infections. Recent advances in antiviral therapy have highlighted the effectiveness of protease inhibitors in curtailing the spread and severity of viral diseases, especially during the ongoing COVID-19 pandemic. It also assesses the current efforts aimed at identifying and developing inhibitors targeting key proteases from major respiratory viruses, including human RVs, AdVs, and (severe acute respiratory syndrome coronavirus-2) SARS-CoV-2. Despite the recent identification of SARS-CoV-2, within the last five years, the scientific community has devoted considerable time and resources to investigate existing drugs and develop new inhibitors targeting the virus\'s main protease. However, research efforts in identifying inhibitors of the proteases of RVs and AdVs are limited. Therefore, herein, it is proposed to utilize this knowledge to develop new inhibitors for the proteases of other viruses affecting the respiratory tract or to develop dual inhibitors. Finally, by detailing the mechanisms of action and therapeutic potentials of these inhibitors, this review aims to demonstrate their significant role in transforming the management of respiratory viral diseases and to offer insights into future research directions.

UNASSIGNED: Before they can produce their own antibodies, newborns are protected from infections by transplacental transfer of maternal IgG antibodies and after birth through breast milk IgA antibodies. Rhinovirus (RV) infections are extremely common in early childhood, and while RV infections often result in only mild upper respiratory illnesses, they can also cause severe lower respiratory illnesses such as bronchiolitis and pneumonia.
UNASSIGNED: We used high-density peptide arrays to profile infant and maternal antibody reactivity to capsid and full proteome sequences of three human RVs - A16, B52, and C11.
UNASSIGNED: Numerous plasma IgG and breast milk IgA RV epitopes were identified that localized to regions of the RV capsid surface and interior, and also to several non-structural proteins. While most epitopes were bound by both IgG and IgA, there were several instances where isotype-specific and RV-specific binding were observed. We also profiled 62 unique RV-C protein loop sequences characteristic of this species\' capsid VP1 protein.
UNASSIGNED: Many of the RV-C loop sequences were highly bound by IgG from one-year-old infants, indicating recent or ongoing active infections, or alternatively, a level of cross-reactivity among homologous RV-C sites.

Although rhinoviruses play a major role in exacerbations of childhood asthma, the presence of rhinovirus (RV) RNA in plasma, referred to as viremia, has been investigated in a few studies. The aim of the study was to investigate the presence of rhinovirus viremia at the time of asthma exacerbation and to describe the molecular characteristics of rhinoviruses associated with viremia. We conducted an observational, prospective, multicenter study in eight pediatric hospitals (VIRASTHMA2). Preschool-aged recurrent wheezers (1-5 years) hospitalized for a severe exacerbation were included. Reverse-transcription polymerase chain reaction (RT-PCR) and molecular typing for RV/enteroviruses (EV) were performed on nasal swabs and plasma. Plasma specimens were available for 105 children with positive RT-PCR for RV/EV in respiratory specimens. Thirty-six (34.3%) had positive viremia. In plasma, 28 (82.4%) of the typable specimens were RV-C, five (14.7%) were EV-D68, and one was RV-A (2.9%). In all cases, the RV/EV type was identical in the plasma and respiratory specimens. In conclusion, RV/EV viremia is frequent in severe exacerbations of preschool recurrent wheezers, particularly in RV-C infections.

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Rhinoviruses (RVs) cause upper respiratory tract infections and pneumonia in children and adults. These non-enveloped viruses contain viral coats of four capsid proteins: VP1, VP2, VP3, and VP4. The canyon on VP1 used cell surface receptor ICAM-1 as the site of attachment and for the internalization of viruses. To date, there has been no drug or vaccine available against RVs. In this study, bioactive natural compounds of rosemary (Salvia rosmarinus L.), which are known for their pharmacological potential, were considered to target the VP1 protein. A total of 30 bioactive natural compounds of rosemary were taken as ligands to target viral proteins. The PkCSM tool was used to detect their adherence to Lipinski\'s rule of five and the ADMET properties of the selected ligands. Further, the CB-Dock tool was used for molecular docking studies between the VP1 protein and ligands. Based on the molecular docking and ADMET profiling results, phenethyl amine (4 methoxy benzyl) was selected as the lead compound. A comparative study was performed between the lead compound and two antiviral drugs, Placonaril and Nitazoxanide, to investigate the higher potential of natural compounds over synthetic drugs. Placonaril also targets VP1 but failed in clinical trials while Nitazoxanide was examined in clinical trials against rhinoviruses. It was discovered from this study that the (4 methoxy benzyl) phenethyl amine exhibited less toxicity in comparison to other tested drugs against RVs. More research is needed to determine its potential and make it a good medication against RVs.

Small molecules that exhibit broad-spectrum enteroviral inhibitory activity by targeting viral replication proteins are highly desired in antiviral drug discovery studies. To discover new human rhinovirus (hRV) inhibitors, we performed a high-throughput screening of 100,000 compounds from the Korea Chemical Bank library. This search led to identification of two phosphatidylinositol-4-kinase IIIβ (PI4KIIIβ) inhibitors having the pyrazolo-pyrimidine core structure, which display moderate anti-rhinoviral activity along with mild cytotoxicity. The results of a study aimed at optimizing the activity of the hit compounds showed that the pyrazolo-pyrimidine derivative 6f exhibits the highest activity (EC50 = 0.044, 0.066, and 0.083 μM for hRV-B14, hRV-A16, and hRV-A21, respectively) and moderate toxicity (CC50 = 31.38 μM). Furthermore, 6f has broad-spectrum activities against various hRVs, coxsackieviruses and other enteroviruses, such as EV-A71, EV-D68. An assessment of kinase inhibition potencies demonstrated that 6f possesses a high and selective kinase inhibition activity against PI4KIIIβ (IC50 value of 0.057 μM) and not against PI4KIIIα (>10 μM). Moreover, 6f exhibits modest hepatic stability (46.9 and 55.3 % remaining after 30 min in mouse and human liver microsomes, respectively). Finally, an in vivo study demonstrated that 6f possesses a desirable pharmacokinetic profile reflected in low systemic clearance (0.48 L∙h-1 kg-1) and modest oral bioavailability (52.4 %). Hence, 6f (KR-26549) appears to be an ideal lead for the development of new antiviral drugs.

BACKGROUND: Viral wheezing is an important risk factor for asthma, which comprises several respiratory phenotypes. We sought to understand if the etiology of early-life wheezing illnesses relates to childhood respiratory and asthma phenotypes.
METHODS: Data were collected prospectively on 429 children in the Urban Environment and Childhood Asthma (URECA) birth cohort study through age 10 years. We identified wheezing illnesses and the corresponding viral etiology (PCR testing of nasal mucus) during the first 3 years of life. Six phenotypes of respiratory health were identified at 10 years of age based on trajectories of wheezing, allergic sensitization, and lung function. We compared the etiology of early wheezing illnesses to these wheezing respiratory phenotypes and the development of asthma.
RESULTS: In the first 3 years of life, at least one virus was detected in 324 (67%) of the 483 wheezing episodes documented in the study cohort. Using hierarchical partitioning we found that non-viral wheezing episodes accounted for the greatest variance in asthma diagnosed at both 7 and 10 years of age (8.0% and 5.8% respectively). Rhinovirus wheezing illnesses explained the most variance in respiratory phenotype outcome followed by non-viral wheezing episodes (4.9% and 3.9% respectively) at 10 years of age.
CONCLUSIONS: Within this high-risk urban-residing cohort in early life, non-viral wheezing episodes were frequently identified and associated with asthma development. Though rhinovirus wheezing illnesses had the greatest association with phenotype outcome, the specific etiology of wheezing episodes in early life provided limited information about subsequent wheezing phenotypes.

PGAP3 is a glycosylphosphatidylinositol (GPI) phospholipase gene localized within chromosome 17q12-21, a region highly linked to asthma. Although much is known about the function of other chromosome 17q12-21 genes expressed at increased levels in bronchial epithelium such as ORMDL3 and GSDMB, little is known about the function of increased PGAP3 expression in bronchial epithelium in the context of asthma. The aim of this study was therefore to determine whether increased PGAP3 expression in human bronchial epithelial cells regulated expression of mRNA pathways important to the pathogenesis of asthma by utilizing RNA-sequencing and bioinformatic analysis. We performed RNA-sequencing on normal human bronchial epithelial cells transfected with PGAP3 for 24 and 48 hours. PGAP3 regulated genes were compared to asthma and respiratory virus (influenza A, rhinovirus, respiratory syncytial virus) reference data sets to identify PGAP3 target genes and pathways. Approximately 9% of the upregulated PGAP3-induced genes were found in an asthma reference data set, 41% in a rhinovirus reference data set, 33% in an influenza A reference data set, and 3% in a respiratory syncytial virus reference data set. PGAP3 significantly upregulated the expression of several genes associated with the innate immune response and viral signatures of respiratory viruses associated with asthma exacerbations. Two of the highest expressed genes induced by PGAP3 are RSAD2, OASL, and IFN-λ, which are anti-viral genes associated with asthma. PGAP3 also upregulated the antiviral gene BST2, which like PGAP3 is a GPI-anchored protein. We conclude that PGAP3 expression in human bronchial epithelial cells regulates expression of genes known to be linked to asthma, and also regulates the bronchial epithelial expression of genes pertinent to the pathogenesis of respiratory viral triggered asthma exacerbations.

In Sicily (Italy), respiratory syncytial virus (RSV), rhinovirus (HRV), and influenza virus triggered epidemics among children, resulting in an increase in acute respiratory tract infections (ARTIs). Our objective was to capture the epidemiology of respiratory infections in children, determining which pathogens were associated with respiratory infections following the lockdown and whether there were changes in the epidemiological landscape during the post-SARS-CoV-2 pandemic era.
METHODS: We analyzed multiplex respiratory viral PCR data (BioFire® FilmArray® Respiratory Panel 2.1 Plus) from 204 children presenting with respiratory symptoms and/or fever to our Unit of Pediatrics and Pediatric Emergency.
RESULTS: Viruses were predominantly responsible for ARTIs (99%), with RSV emerging as the most common agent involved in respiratory infections, followed by human rhinovirus/enterovirus and influenza A. RSV and rhinovirus were also the primary agents in coinfections. RSV predominated during winter months, while HRV/EV exhibited greater prevalence than RSV during the fall. Some viruses spread exclusively in coinfections (human coronavirus NL63, adenovirus, metapneumovirus, and parainfluenza viruses 1-3), while others primarily caused mono-infections (influenza A and B). SARS-CoV-2 was detected equally in both mono-infections (41%) and coinfections (59%).
CONCLUSIONS: Our analysis underlines the predominance of RSV and the importance of implementing preventive strategies for RSV.