Prevention Of Respiratory Syncytial Virus Infection Research Articles

Learn from international recommendations and experiences of countries that have successfully implemented monoclonal antibody prophylaxis for prevention of RSV infection.

Respiratory syncytial virus (RSV)-mediated bronchiolitis causes a significant global health burden. Despite this, for several years, the only approved agent for RSV prophylaxis was the anti-RSV monoclonal antibody Palivizumab, reserved for a small population of infants at high risk of developing severe RSV disease. Recently, the availability and approval of nirsevimab to immunize all infants against RSV infection since their first RSV season represented a crucial paradigm shift in RSV prevention. Nirsevimab has been shown to be safe and effective (> 80%) against RSV lower respiratory tract infections (LRTIs) in all infants and children at their first season of RSV. Surveillance studies have demonstrated 90% effectiveness in reducing all-cause hospitalizations, all-cause LRTI hospitalizations, RSV-related LRTI hospitalizations, and severe RSV-related LRTIs. Moreover, the consistency and reproducibility of the beneficial outcomes coming from the prophylaxis with nirsevimab highlights its potential to deliver substantial health benefits, positioning monoclonal antibody administration as a cornerstone in the fight against RSV-related morbidity and mortality. Implementing immunization strategies for infants and children is crucial to align the international experiences and guarantee universal protection. This review provided an updated overview of the monoclonal antibody strategy for preventing RSV infection.

Respiratory syncytial virus infections in adults.

Respiratory syncytial virus (RSV) infections as an important cause of acute respiratory illness (ARI) and exacerbation of chronic lung disease in adults especially affect older adults, adults with immunosuppression, and adults with chronic disease, particularly pulmonary or cardiac disease, who may develop more severe complications. A more accurate determination of the burden of RSV infection in the adult population would improve the approach to infection, especially considering the growth of the older adult population in the world and, above all, that there are currently three approved vaccines aimed at the adult population that could have an effect on the prevention of RSV infection. This review article reviews the most relevant and novel scientific evidence on the epidemiology, diagnosis, treatment and prevention of RSV infection in the adult population.

Recommendation for the use of respiratory syncytial virus vaccines.

Respiratory syncytial virus (RSV) is the most common pathogen for young children hospitalized with bronchiolitis and pneumonia. Most infections occur below 1 year of age. RSV is also a significant viral pathogen for adults with respiratory tract infection. Vaccines targeting the pre-fusion protein of RSV, including recombinant and mRNA vaccines, are now available. A committee of experts from related fields was convened by the Taiwan Immunization Vision and Strategy to develop recommendations for RSV vaccination in the elderly and pregnant women. The recommendation is not intended as a sole source of guidance in the prevention of RSV infection in children. The provisions listed in this recommendation are comprehensive suggestions made by experts in Taiwan based on existing medical evidence. This recommendation should be subject to modification in light of additional medical research findings in the future, and these provisions should not be cited as a basis for dispute resolution.

Respiratory syncytial virus pulmonary infections in adults - disease burden and prevention.

We highlight the evolving understanding of the burden of respiratory syncytial virus (RSV) in older adults and recent data on the three new vaccines. As well as a greater recognition of the amount of RSV infection in adults, and especially over 60 years of age, there has been a significant amount of study detailing the postacute burden including excess cardiovascular disease and loss of physical and cognitive functioning. Three new RSV vaccines now have published data for two seasons, and while direct comparison is not possible due to differences in the timing, methodology and populations studies, all show good efficacy with no serious side effects of concern. RSV causes a substantial amount of morbidity and mortality in older adults with both acute and longer term impacts. With effective vaccines now available clinicians should be advocating with their patients to prevent RSV infection.

Coumarins and Hesperetin Inhibit Human Respiratory Syncytial Virus Infection.

Respiratory syncytial virus (RSV) is one of the most prevalent viruses that causes severe acute lower respiratory tract infections (ALRTIs) in the elderly and young children. There is no specific drug to treat RSV, only a broad-spectrum antiviral, ribavirin, which is only used in critical cases. Our research group is investigating antiviral agents of natural origin, such as coumarins and flavonoids, that may help reduce or prevent RSV infection. The cytotoxic concentrations of coumarins and hesperetin were tested on A549 and HEp-2 cells and used in inhibition tests in which 80% of the cells were viable. The anti-RSV action of the molecules was analyzed in A549 and HEp-2 cells and in HBE cell cultures infected with RSV-luc or rgRSV. We also encapsulated the compounds using β-cyclodextrin to improve the permeability and solubility of the molecules. Esculetin and 4-methyl inhibited rgRSV effectively on A549 and HEp-2 cells after 24 hpi, and when they were encapsulated, coumarin, esculetin, and hesperetin presented inhibition against rgRSV in HBE culture. The coumarins inhibit RSV replication in cell culture and even manage to overcome the mucus barriers of the HBE cultures, and β-cyclodextrin was essential for some of the coumarins to enter the cell and therefore to reach their targets.

Prophylaxis of respiratory syncytial virus infection: current status and prospects for vaccine development

INTRODUCTION. Respiratory syncytial virus (RSV) is one of the most widespread pathogens that typically cause acute upper and lower respiratory tract infections in children and adults. Monoclonal antibody products have long been used for passive immunoprophylaxis in premature infants with bronchopulmonary dysplasia. However, vaccines have recently been licensed for the prophylactic immunisation of older adults with various risk factors for severe RSV infection (primarily, chronic cardiovascular and respiratory diseases and diabetes mellitus).AIM. This study aimed to review the current status of the development of vaccines for active immunisation against RSV infection, including the epidemiological rationale for their development, clinical trial results for licensed vaccines, recommendations for vaccination, and promising pipeline vaccines for RSV prevention.DISCUSSION. Initially hindered by the unique immunopathogenesis of RSV infection and the genetic hypervariability of RSV for a long time, attempts to develop an RSV vaccine succeeded when international researchers managed to identify a conservative neutralising antibody target capable of inducing specific immunity against RSV. This target, the RSV capsid protein stabilised in its prefusion (pre-F) conformation, can mediate viral entry into the cell following a conformational change. Several subunit vaccines based on recombinant pre-F proteins have successfully passed clinical trials and have been approved for the immunisation of older adults. In addition, one of these vaccines has been recommended for use during pregnancy to prevent RSV infection in newborns and infants. Currently, programmes are being implemented to develop novel RSV vaccines based on messenger RNA (mRNA) and non-replicating attenuated influenza vectors. This article examines and summarises the efficacy and safety parameters of two RSV vaccines approved in multiple countries around the world. Both vaccines have satisfactory safety profiles and comparable prophylactic efficacy parameters.CONCLUSIONS. Prelicensure clinical trials of novel RSV vaccines, including those being developed in the Russian Federation, should include prophylactic efficacy assessments in target patient populations. For vaccines approved by leading international regulators, clinical trials required for approval in the Russian Federation will be limited to bridging studies confirming the immunogenicity and safety of the vaccines.

Prevention of respiratory syncytial virus from 1991 to 2024: a systematic review and bibliometrics analysis.

Respiratory syncytial virus (RSV) puts children and elderly individuals worldwide at risk for severe health issues and financial difficulties. Prevention is the main treatment for RSV infection, as there is currently no particular therapy. By using bibliometrics analysis, this study attempted to map the increasing tendency in the prevention of RSV infection from January 1991 to August 2024 and to examine the frontiers and hotspots of related research. We extracted pertinent articles through the Web of Science Core Collection (WoSCC) on August 26, 2024, covering the period between January 1991 and August 2024. Then, an online bibliometrix interface (https://bibliometrics.com), R software (version 4.3.2), CiteSpace V6.1R6 (64-bit) software, and the Online Analysis Platform of Literature Metrology were used to analyze the data. A total of 709 eligible data points pertaining to the prevention of RSV were included. The United States, England, and the Netherlands were the three major contributors to this field. The most productive journal was Vaccine. Centers for Disease Control and Prevention ranked first, with 22 publications in this field. The fusion (F) protein, nonstructural (NS) protein and glycoprotein (G) protein are the target proteins of RSV prevention drugs. In the past 30 years, the research on RSV prevention has entered a stage of rapid development, and many vaccines and monoclonal antibodies have entered the clinical research stage, and some have been marketed.

Comparison of clinical characteristics and outcomes in hospitalized adult patients infected with respiratory syncytial virus and influenza virus

Background Because patients infected with respiratory syncytial virus (RSV) have been reported to be older than patients infected with influenza virus, the more frequent incidence of complications in RSV-infected patients may be age-related. This study compared clinical characteristics and outcomes in hospitalized adults infected with RSV with findings in age- and sex-matched adults infected with influenza virus. Methods The medical records of hospitalized adult patients infected with RSV or influenza virus at two university hospitals from 2013 to 2022 were retrospectively analyzed. Virus infection was confirmed by real-time polymerase chain reaction. Each RSV-infected patient was matched by age and sex with two influenza virus-infected patients, and their clinical symptoms, laboratory parameters and hospital courses were compared. Results The study cohort consisted of 552 patients, 184 infected with RSV and 368 infected with influenza virus. Fever (71.2% vs. 79.9%, p = .022) and cough (70.1% vs. 80.4%, p = .007) were significantly less frequent in the RSV than in the influenza group, whereas white blood cell counts (9132/mm3 vs. 7616/mm3, p < .001) and C-reactive protein concentrations (10.25 vs. 8.88 mg/dL, p = .029) were significantly higher in the RSV group. The frequency of oxygen therapy was higher (60.3% vs. 48.6%, p = .010) and hospital stay was longer (8 vs. 6 days, p = .003) in RSV than in influenza virus-infected patients. Conclusions Clinical symptoms were less frequent, but disease was more severe, in hospitalized adult patients infected with RSV than in age- and sex-matched patients infected with influenza. Greater attention should be paid to diagnosing and preventing RSV infection in adults.

Confronting the challenge: a regional perspective by the Latin American pediatric infectious diseases society (SLIPE) expert group on respiratory syncytial virus-tackling the burden of disease and implementing preventive solutions.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections in children around the world. The post-pandemic era has resulted in a notable increase in reported cases of RSV infections, co-circulation of other respiratory viruses, shifts in epidemiology, altered respiratory season timing, and increased healthcare demand. Low- and middle-income countries are responsible for the highest burden of RSV disease, contributing significantly to health expenses during respiratory seasons and RSV-associated mortality in children. Until recently, supportive measures were the only intervention to treat or prevent RSV-infection, since preventive strategies like palivizumab are limited for high-risk populations. Advances in new available strategies, such as long-acting monoclonal antibodies during the neonatal period and vaccination of pregnant women, are now a reality. As the Regional Expert Group of the Latin American Pediatric Infectious Diseases Society (SLIPE), we sought to evaluate the burden of RSV infection in Latin America and the Caribbean (LAC) region, analyze current strategies to prevent RSV infection in children, and provide recommendations for implementing new strategies for preventing RSV infection in children in LAC region.

Cold-adapted influenza vaccine carrying three repeats of a respiratory syncytial virus (RSV) fusion glycoprotein epitope site protects BALB/c mice and cotton rats against RSV infection

Respiratory syncytial virus is the major cause of respiratory viral infections, particularly in infants, immunocompromised populations, and the elderly (over 65 years old), the prevention of RSV infection has become a priority. In this study, we generated a chimeric influenza virus, termed LAIV/RSV/HA-3F, using reverse genetics technology which contained three repeats of the RSV fusion protein neutralizing epitope site II to the N terminal in the background of the hemagglutinin (HA) gene of cold adapted influenza vaccine A/California/7/2009 ca. LAIV/RSV/HA-3F exhibited cold-adapted (ca) and attenuated (att) phenotype. BALB/c mice immunized intranasally with LAIV/RSV/HA-3F showed robust immunogenicity, inducing viral-specific antibody responses against both influenza and RSV, eliciting RSV-specific humoral, cellular and mucosal immune responses. LAIV/RSV/HA-3F also conferred protection as indicated by reduced viral titers and improved lung histopathological alterations against live RSV virus challenge. Mechanismly, single-cell RNA sequencing (scRNA-seq) and single-cell T cell antigen receptor (TCR) sequencing were employed to characterize the immune responses triggered by chimeric RSV vaccine, displaying that LAIV/RSV/HA-3F provided protection mainly via interferon-γ (IFN-γ). Moreover, we found that LAIV/RSV/HA-3F significantly inhibited viral replication in the challenged lung and protected against subsequent RSV challenge in cotton rats without causing lung disease. Taken together, our findings demonstrated that LAIV/RSV/HA-3F has potential as a promising bivalent vaccine with dual purpose candidate for the prevention of influenza and RSV, and preclinical and clinical studies warrant further investigations.

Generation of novel respiratory syncytial virus vaccine candidate antigens that can induce high levels of prefusion-specific antibodies

Respiratory syncytial virus (RSV) infection is an acute respiratory infection caused by RSV. It occurs worldwide, and for over 50 years, several attempts have been made to research and develop vaccines to prevent RSV infection; effective preventive vaccines are eagerly awaited. The RSV fusion (F) protein, which has gained attention as a vaccine antigen, causes a dynamic structural change from the preF to postF state. Therefore, the structural changes in proteins must be regulated to produce a vaccine antigen that can efficiently induce antibodies with high virus-neutralizing activity. We successfully discovered several mutations that stabilized the antigen site Ø in the preF state, trimerized it, and improved the level of protein expression through observation and computational analysis of the RSV-F protein structure and amino acid mutation analysis of RSV strains. The four RSV-F protein mutants that resulted from the combination of these effective mutations stably conserved a wide range of preF- and trimeric preF-specific epitopes with high virus-neutralizing activity. Absorption assay using human serum revealed that mutants constructed bound to antibodies with virus-neutralizing activity that were induced by natural RSV infection, whereas they hardly bound to anti-postF antibodies without virus-neutralizing activity. Furthermore, mouse immunization demonstrated that our constructed mutants induced a high percentage of antibodies that bind to the preF-specific antigen site. These characteristics suggest that the mutants constructed can be superior vaccine antigens from the viewpoint of RSV infection prevention effect and safety.

Cost-utility analysis of palivizumab for preventing respiratory syncytial virus in preterm neonates and infants in Colombia

AimPalivizumab has proven effective in reducing hospitalizations, preventing severe illness, improving health outcomes, and reducing healthcare costs for infants at risk of respiratory syncytial virus (RSV) infection. We aim to assess the value of palivizumab in preventing RSV infection in high-risk infants in Colombia, where RSV poses a significant threat, causing severe respiratory illness and hospitalizations.MethodsWe conducted a decision tree analysis to compare five doses of palivizumab with no palivizumab. The study considered three population groups: preterm neonates (≤ 35 weeks gestational age), infants with bronchopulmonary dysplasia (BPD), and infants with hemodynamically significant congenital heart disease (CHD). We obtained clinical efficacy data from IMpact-RSV and Cardiac Synagis trials, while we derived neonatal hospitalization risks from the SENTINEL-1 study. We based hospitalization and recurrent wheezing management costs on Colombian analyses and validated them by experts. We estimated incremental cost-effectiveness ratios and performed 1,000 Monte Carlo simulations for probabilistic sensitivity analyses.ResultsPalivizumab is a dominant strategy for preventing RSV infection in preterm neonates and infants with BPD and CHD. Its high efficacy (78% in preventing RSV in preterm infants), the substantial risk of illness and hospitalization, and the high costs associated with hospitalization, particularly in neonatal intensive care settings, support this finding. The scatter plots and willingness-to-pay curves align with these results.ConclusionPalivizumab is a cost-saving strategy in Colombia, effectively preventing RSV infection in preterm neonates and infants with BPD and CHD by reducing hospitalizations and lowering healthcare costs.

Exploratory analysis of the economically justifiable price of nirsevimab for healthy late-preterm and term infants in Colombia.

Respiratory syncytial virus infection is the leading cause of lower respiratory infection globally. Recently, nirsevimab has been approved to prevent respiratory syncytial virus (RSV) infection. This study explores the economically justifiable price of nirsevimab for preventing RSV infection in Colombia's children under 1 year of age. A static model was developed using the decision tree microsimulation to estimate the quality-adjusted costs and life years of two interventions: a single intramuscular dose of nirsevimab versus not applying nirsevimab. This analysis was made during a time horizon of 1 year and from a societal perspective. The annual savings in Colombia associated with this cost per dose ranged from U$ 2.5 to 4.1 million. Based on thresholds of U$ 4828, U$ 5128, and U$ 19 992 per QALY evaluated in this study, we established economically justifiable drug acquisition prices of U$ 21.88, U$ 25.04, and U$ 44.02 per dose of nirsevimab. the economically justifiable cost for nirsevimab in Colombia is between U$ 21 to U$ 44 per dose, depending on the willingness to pay used to decide its implementation. This result should encourage more studies in the region that optimize decision-making processes when incorporating this drug into the health plans of each country.

Эффективность иммунопрофилактики респираторно-синцитиальной вирусной инфекции препаратом паливизумаб у недоношенных детей: результаты одноцентрового когортного ретроспективного исследования

Preterm infants born before the 35th week of gestation are at high risk of severe respiratory syncytial virus (RSV) infection. Passive immunoprophylaxis with palivizumab, a monoclonal antibody against RSV, is currently recognized as the most effective measure to prevent RSV infection. The objective of the study was to evaluate the efficacy of prophylactic use of palivizumab in premature infants at high risk of severe RSVI. Patients and methods. A single-center retrospective cohort study conducted on the basis of the Catamnesis Cabinet of the Republican Clinical Perinatal Center (Ufa) included 516 premature children with gestational age less than 35 weeks who reached the age of 1 year of life from April 2020 to April 2022. 250 children were included in the "immunization+" group, and 266 children were included in the "immunization-" group. In both groups, the proportion of children who went to the outpatient clinic for acute respiratory infection (ARI) and the proportion of children hospitalized for lower respiratory tract infection (LRTI) were determined. Results. Among the immunized, the proportion of children presenting to the outpatient clinic for ARI was lower than among the non-immunized, 63.6% and 82.0%, respectively (p &lt; 0.001; OR 0.77; 95% CI 0.69-0.86). There was no statistically significant reduction in the rate of hospitalization of preterm infants due to LRTI overall. However, the proportion of children hospitalized for bronchitis was lower among the immunized than among the non-immunized, 24.0 and 31.6%, respectively (p = 0.045; HR 0.74; 95% CI 0.55-0.99). The greatest effect of palivizumab immunization was observed in children born at 32 weeks' gestation or less who received 3-5 injections of the drug. Conclusion. This study demonstrated the efficacy of immunoprophylaxis with palivizumab in premature infants of the first year of life from the high-risk group of severe RSVI. Key words: respiratory syncytial virus, acute respiratory infection, hospitalization, premature infants, high-risk group, immunoprophylaxis, palivizumab

Respiratory Syncytial Virus: Transmission and Treatment

Respiratory Syncytial Virus (RSV), a respiratory tract infection-causing virus with a global distribution and seasonal occurrence, is the second leading cause of death in children under one year old, after malaria. The Respiratory Syncytial virus is an enveloped negative-strand RNA virus from the Paramyxoviridae family primarily transmitted by droplets of a cough or sneeze. However, kisses between infected and healthy individuals can also rapidly spread the virus, especially among children. Typically, the virus causes symptoms such as coughing, sneezing, or a fever making it visibly like other infections or conditions. Young children may have apnea and overall be irritable. Confirmation of RSV diagnosis can be done through available RSV-card tests or through RT-PCR tests. Though there is no standard treatment for RSV infection, drugs such as Ribavirin and Synagis (Palivizumab) are currently used for managing symptoms of RSV infection in areas that have access to such medications. Palivizumab is used to treat prophylaxis, the prevention of serious lower respiratory tract disease brought on by RSV in children at high risk of RSV disease, is the greatest preventative approach. Numerous clinical studies are being conducted right now to treat and prevent RSV infection. Most of the study focuses on children below the age of 5 years because they are the most vulnerable, but there is also research on the prevalence of RSV in older adults and the effects of maternal vaccination on infants through the antibodies made to fight against RSV infection. G protein, F protein, and SH protein are three crucial membrane proteins that make up the RSV structure. A vaccine containing both the F and G RSV proteins would offer more protection against RSV. The F and G protein stimulates antibody formation, which neutralizes the virus. The RSV treatment plans and vaccine trials within India, South Africa, the United States of America, and the United Kingdom show similarities and differences that could be utilized to develop a treatment plan for RSV. In the upcoming years, further research is required to produce a cheaper alternative that is accessible to all countries. This will help to establish a set, effective protocol for RSV to be used worldwide.

The RSVPreF3-AS01 vaccine elicits broad neutralization of contemporary and antigenically distant respiratory syncytial virus strains.

The RSVPreF3-AS01 vaccine, containing the respiratory syncytial virus (RSV) prefusion F protein and the AS01 adjuvant, was previously shown to boost neutralization responses against historical RSV strains and to be efficacious in preventing RSV-associated lower respiratory tract diseases in older adults. Although RSV F is highly conserved, variation does exist between strains. Here, we characterized variations in the major viral antigenic sites among contemporary RSV sequences when compared with RSVPreF3 and showed that, in older adults, RSVPreF3-AS01 broadly boosts neutralization responses against currently dominant and antigenically distant RSV strains. RSV-neutralizing responses are thought to play a central role in preventing RSV infection. Therefore, the breadth of RSVPreF3-AS01-elicited neutralization responses may contribute to vaccine efficacy against contemporary RSV strains and those that may emerge in the future.

A Pseudovirus-Based Entry Assay to Evaluate Neutralizing Activity against Respiratory Syncytial Virus.

Respiratory syncytial virus (RSV) infection can cause life-threatening pneumonia and bronchiolitis, posing a significant threat to human health worldwide, especially to children and the elderly. Currently, there is no specific treatment for RSV infection. The most effective measures for preventing RSV infection are vaccines and prophylactic medications. However, not all population groups are eligible for the approved vaccines or antibody-based preventive medications. Therefore, there is an urgent need to develop novel vaccines and prophylactic drugs available for people of all ages. High-throughput assays that evaluate the efficacy of viral entry inhibitors or vaccine-induced neutralizing antibodies in blocking RSV entry are crucial for evaluating vaccine and prophylactic drug candidates. We developed an efficient entry assay using a lentiviral pseudovirus carrying the fusion (F) protein of type A or B RSV. In addition, the essential parameters were systematically optimized, including the number of transfected plasmids, storage conditions of the pseudovirus, cell types, cell numbers, virus inoculum, and time point of detection. Furthermore, the convalescent sera exhibited comparable inhibitory activity in this assay as in the authentic RSV virus neutralization assay. We established a robust pseudovirus-based entry assay for RSV, which holds excellent promise for studying entry mechanisms, evaluating viral entry inhibitors, and assessing vaccine-elicited neutralizing antibodies against RSV.

RESPIRATORY SYNCYTIAL VIRUS PATHOLOGY, TREATMENT AND POSSIBILITY OF PROPHYLAXIS BY VACCINATION

Background: Respiratory Syncytial Virus (RSV) is one of the main causes of morbidity and mortality among children under one year old, in the context of lower respiratory tract infections (LRTIs) of viral etiology. RSV belongs to the family Pneumoviridae, order Mononegavirales and is a filamentous enveloped virus in the genus Orthopneumovirus. Methods: We screened PubMed, PubMed Central (PMC), ScienceDirect and Google Scholar clinical trials in different phases and several national and international guidelines on the subject of treatment and prevention of RSV infections, using specific keywords. Results: Several methods have been tried over time to achieve primary prophylaxis in the case of RSV. Longacting monoclonal antibodies (mAbs), active immunization of children and passive immunization of newborns through maternal immunization were among the tested methods. For the geriatric and immunocompromised patients, three approaches were used in the search for a vaccine: nucleic acids, subunits of the nucleic acids and other vectors to create a safe and efficient product. For the groups at risk, RSV immunization would be the most efficient form of prevention. As a result, understanding the viral structure and its interaction at the cellular level is critical. The virus can connect to a variety of receptors, demonstrating the complexity of the pathogenic process by which it expresses itself, CX3 chemokine receptor 1 (CX3CR1), annexin II and Toll-like receptors being among the most well-known. Conclusions: Although multiple vaccines are being tested in clinical trials for neonates, geriatric patients and patients with comorbidities, none is currently licensed. Palivizumab, a monoclonal antibody authorized in 1998, is now used for prophylaxis.

Immunoinformatics aided approach for predicting potent cytotoxic T cell epitopes of respiratory syncytial virus

Respiratory syncytial virus (RSV) is an infectious viral pathogen that causing serious respiratory infection in adults and neonates. The only approved therapies for RSV are the monoclonal antibodies palivizumab and its derivative motavizumab. Both treatments are expensive and require a hospital setting for administration. A vaccine represents a safe, effective and cheaper alternative for preventing RSV infection. In silico prediction methods have proven to be valuable in speeding up the process of vaccine design. In this study, reverse vaccinology methods were used to predict the cytotoxic T lymphocytes (CTL) epitopes from the entire proteome of RSV strain A. From amongst 3402 predicted binders to 12 high frequency alleles from the Immune Epitope Database (IEDB), 567 had positive processing scores while 327 epitopes were predicted to be immunogenic. A thorough examination of the 327 epitopes for possible antigenicity, allergenicity and toxicity resulted in 95 epitopes with desirable properties. A BLASTp analysis revealed 94 unique and non-homologous epitopes that were subjected to molecular docking across the 12 high frequency alleles. The final dataset of 70 epitopes contained 13 experimentally proven and 57 unique epitopes from a total of 11 RSV proteins. From our findings on selected T-cell-specific RSV antigen epitopes, notably the four epitopes confirmed to exhibit stable binding by molecular dynamics. The prediction pipeline used in this study represents an effective way to screen the immunogenic epitopes from other pathogens. Communicated by Ramaswamy H. Sarma

Threat of respiratory syncytial virus infection knocking the door: a proposed potential drug candidate through molecular dynamics simulations, a future alternative.

The discovery of antiviral approaches to prevent or cure respiratory syncytial virus (RSV) infections is critical, particularly because RSV is one of the most common causes of infant respiratory problems. There is currently no approved vaccination available to treat RSV infections. FDA has approved the drug ribavirin, but it is not sufficient to treat RSV. This work aimed to find and study in silico anti-RSV drugs that target matrix protein and nucleoprotein. In this study, we have identified five drug candidates that had better binding energies than ribavirin. Garenoxacin appeared as top lead compounds between them. AutoDock Vina was used to execute molecular docking of a library of chosen chemicals. The high-score compound was then confirmed using the Maestro 12.3 module's molecular dynamics simulation and the binding energies derived using Prime/Molecular Mechanics Generalized Born Surface Area (Prime/MM-GBSA). Comparative molecular dynamics simulations revealed that garenoxacin has better stability and high residue contacts with high binding affinity than ribavirin. This study showed garenoxacin could prevent RSV infection better than ribavirin. In pursuing a more effective RSV control drug, additional research into these chemicals in vitro and in vivo is essential.