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Respiratory Syncytial Virus (RSV) poses a major health threat to older adults, pregnant women, and high-risk populations. We systematically evaluated the efficacy, immunogenicity, and safety of three FDA-approved RSV vaccines: Arexvy, Abrysvo, and mResvia. Following PRISMA 2020 guidelines, we searched PubMed, ClinicalTrials.gov, FDA, and Vaccine Adverse Event Reporting System (VAERS) up to March 2025. Of 1,250 identified records, 24 studies (14 RCTs, 7 observational, 3 post-marketing) met inclusion criteria. Risk of bias was assessed using the Cochrane RoB tool and Newcastle-Ottawa Scale. PROSPERO registration: CRD420250651132. Included studies enrolled over 50,000 participants across North America, Europe, Asia, and Latin America. Arexvy reduced RSV-related hospitalizations in older adults by 60-65% (95% CI: 56-66%); Abrysvo showed 58-63% efficacy in older adults and 68-72% protection against infant RSV hospitalization via maternal immunization. mResvia demonstrated 55-58% efficacy against RSV illness. All vaccines induced 5-7-fold increases in neutralizing antibody titers, with responses sustained for up to 12 months. Safety profiles were favorable: local injection site pain occurred in ~23-29%, systemic symptoms in 7-11%, and serious adverse events in <1%. No new safety concerns were identified in post-marketing surveillance. FDA-approved RSV vaccines provide robust protection against RSV in high-risk populations, with sustained immunogenicity and acceptable safety. While findings are promising, generalizability to underserved regions remains limited, and long-term effectiveness data are still emerging. Continued real-world monitoring and head-to-head comparisons are needed to inform global immunization strategies. https://www.crd.york.ac.uk/PROSPERO/view/, identifier CRD420250651132.

Antibodies represent indispensable tools in the armamentarium against infectious diseases, with widespread application in prophylactic, therapeutic, and diagnostic settings. Conventional mammalian immunoglobulin G (IgG) antibodies have been extensively utilized in clinical and research contexts; however, their utility is sometimes constrained by intrinsic limitations such as thermal instability, susceptibility to proteolytic degradation, limited mucosal efficacy, and the high costs associated with mammalian expression systems. These challenges have driven increasing interest in alternative antibody formats derived from non-mammalian species that offer distinct structural and functional advantages. In recent years, a growing body of research has focused on non-canonical immunoglobulins, including immunoglobulin Y (IgY) from birds, nanobodies derived from the variable domain of heavy-chain-only antibodies (VHH) in camelids, and variable new antigen receptors (VNARs) sourced from the immunoglobulin new antigen receptor (IgNAR) system in cartilaginous fish such as sharks. The structural simplicity and functional robustness of these antibody platforms enable their integration into diverse biomedical applications, encompassing passive immunization, targeted drug delivery, and point-of-care diagnostics. Indeed, these molecules exhibit unique biochemical properties, including superior thermal and protease resistance, small molecular size, and the ability to access recessed or conformational epitopes that are often inaccessible to conventional IgG antibodies. Moreover, their typically lower immunogenic profiles and reduced pro-inflammatory activity render them suitable for a broad range of therapeutic strategies, including repeated administration and mucosal delivery, and position them as particularly promising agents for combating respiratory pathogens. This review highlights the unique properties, practical advantages, and translational therapeutic potential of IgY, nanobodies, and VNARs. It underscores their advantages over traditional antibody formats and their emerging role as next-generation Immunotherapeutics in the global effort to address persistent and emerging respiratory viral threats.

Monkeypox virus (MPXV) is a member of the Orthopoxvirus genus and the Poxviridae family, which instigated a rising epidemic called monkeypox disease. Proteinases are majorly engaged in viral propagation by catalyzing the cleavage of precursor polyproteins. Therefore, proteinase is essential for monkeypox and a critical drug target. In this study, high-throughput virtual screening (HTVS) and molecular dynamics simulation were applied to detect the potential natural compounds against the proteinase of the monkeypox virus. Here, 32,552 natural products were screened, and the top five compounds were selected after implementing the HTVS and molecular docking protocols in series. Gallicynoic Acid F showed the minimum binding score of −10.56 kcal/mole in the extra precision scoring method, which reflected the highest binding with the protein. The top five compounds showed binding scores ≤−8.98 kcal/mole. These compound complexes were tested under 100 ns molecular dynamics simulation, and Vaccinol M showed the most stable and consistent RMSD trend in the range of 2 Å to 3 Å. Later, MM/GBSA binding free energy and principal component analysis were performed on the top five compounds to validate the stability of selected compound complexes. Moreover, the ligands Gallicynoic Acid F and H2-Erythro-Neopterin showed the lowest binding free energies of −61.42 kcal/mol and −61.09 kcal/mol, respectively. Compared to the native ligand TTP-6171 (ΔGBind = −53.86 kcal/mol), these two compounds showed preferable binding free energy, suggesting inhibitory application against MPXV proteinase. This study proposed natural molecules as a therapeutic solution to control monkeypox disease.

Monkeypox viral infection is an emerging threat and a major concern for the human population. The lack of drug molecules to treat this disease may worsen the problem. Identifying potential drug targets can significantly improve the process of developing potent drug molecules for treating monkeypox. The proteins responsible for viral replication are attractive drug targets. Identifying potential inhibitors from known drug molecules that target these proteins can be key to finding a cure for monkeypox. In this work, two viral proteins, DNA-dependent RNA polymerase (DdRp) and viral core cysteine proteinase, were considered as potential drug targets. Sixteen antibiotic drugs from the tetracycline class were screened against both viral proteins through high-throughput virtual screening. These tetracycline class of antibiotic drugs have the ability to inhibit bacterial protein synthesis, which makes these antibiotics drugs a prominent candidate for drug repurposing. Based on the screening result obtained against DdRp, top two compounds, namely Tigecycline and Eravacycline with docking scores of − 8.88 and − 7.87 kcal/mol, respectively, were selected for further analysis. Omadacycline and minocycline, with docking scores of − 10.60 and − 7.51 kcal/mol, are the top two compounds obtained after screening proteinase with the drug library. These compounds, along with reference compounds GTP for DdRp and tecovirimat for proteinase, were used to form protein–ligand complexes, followed by their evaluation through a 300 ns molecular dynamic simulation. The MM/GBSA binding free energy calculation and principal components analysis of these selected complexes were also conducted for understanding the dynamic stability and binding affinity of these compounds with respective target proteins. Overall, this study demonstrates the repurposing of tetracycline-derived drugs as a therapeutic solution for monkeypox viral infection.

Japanese encephalitis (JE) virus is a flavivirus causing encephalitis causing neurological damage. RNA-dependent-RNA-polymerase (RdRp) is responsible for genome replication making it excellent anti-viral target. In this study, the crystal structure of JE RdRp (jRdRp) and bioflavonoids reported in Azadirachta indica were retrieved from specific databases. Structure-based virtual screening was employed using MTiOpenScreen server and top four compounds selected with the most negative docking scores. Conformations were redocked using AutoDock Vina; these complexes showed mechanistic interactions with Arg 474 , Gly 605 , Asp 668 , and Trp 800 residues in the active site of jRdRp, i.e., guanosine-5′-triphosphate. Furthermore, 100 ns classical molecular dynamics simulation and binding free energy calculation showed stability of docked bioflavonoids in the active jRdRp pocket and significant contribution of van-der-Waals interactions for docked complex stability during simulation. Therefore, this study predicted the anti-viral activity of Gedunin, Nimbolide, Ohchinin acetate, and Kulactone against jRdRp and can be considered for further antiviral drug development.

During the COVID-19 pandemic, governments in many countries worldwide, including India, imposed several restriction measures, including lockdowns, to prevent the spread of the infection. COVID-19 lockdowns led to a reduction in gaseous and particulate pollutants in ambient air. In the present study, we investigated the substantial changes in selected volatile organic compounds (VOCs) after the outbreak of the coronavirus pandemic and associations with health risk assessments in industrial areas. VOC data from 1 January 2019 to 31 December 2021 were collected from the Central Pollution Control Board (CPCB) website, to identify percentage changes in VOC levels before, during, and after COVID-19. The mean TVOC levels at all monitoring stations were 47.22 ± 30.15, 37.19 ± 37.19, and 32.81 ± 32.81 µg/m3 for 2019, 2020, and 2021, respectively. As a result, the TVOC levels gradually declined in consecutive years due to the pandemic in India. The mean TVOC levels at all monitoring stations declined from 9 to 61% during the pandemic period as compared with the pre-pandemic period. In the current study, the T/B ratio values ranged from 2.16 (PG) to 26.38 (NL), which indicated that the major pollutant contributors were traffic and non-traffic sources during the pre-pandemic period. The present findings indicated that TVOC levels had positive but low correlations with SR, BP, RF, and WD, with correlation coefficients (r) of 0.034, 0.118, 0.012, and 0.007, respectively, whereas negative correlations were observed with AT and WS, with correlation coefficients (r) of −0.168 and −0.150, respectively. The lifetime cancer risk (LCR) value for benzene was reported to be higher in children, followed by females and males, for the pre-pandemic, pandemic, and post-pandemic periods. A nationwide scale-up of this study’s findings might be useful in formulating future air pollution reduction policies associated with a reduction in health risk factors. Furthermore, the present study provides baseline data for future studies on the impacts of anthropogenic activities on the air quality of a region.

Human Metapneumovirus (HMPV) is a major contributor to acute respiratory tract infections, particularly affecting children, the elderly, and immunocompromised individuals. Despite its global prevalence, no specific antiviral treatments or vaccines are available, highlighting the urgent need for effective therapeutic interventions. This study utilized a comprehensive computational drug discovery approach to identify potential inhibitors targeting the highly conserved nucleocapsid (N) protein of HMPV, a crucial component in viral replication and transcription. A virtual screening of 1,227 natural compounds from the NP-lib database was performed, identifying MOLPORT-001-742-110, MOLPORT-001-812-855, and MOLPORT-001-740-100 as the top candidates based on their docking scores and binding energies. The initial results were validated through re-docking, molecular interaction analysis, and molecular dynamics (MD) simulations. MOLPORT-001-742-110 demonstrated the highest stability with minimal deviations in Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuation (RMSF) analyses, as well as a well-defined low-energy conformation in the Free Energy Landscape (FEL). Key hydrogen bonds and hydrophobic interactions were retained, reinforcing its strong binding affinity. Principal Component Analysis (PCA) and superimposition studies further supported the stability and adaptability of these compounds within the binding site. Comparative analyses with the control compound confirmed the superior inhibitory potential of the selected ligands, particularly MOLPORT-001-742-110. This study underscores the utility of computational approaches in identifying natural product-based inhibitors and provides a foundation for experimental validation and development of antiviral therapies against HMPV.

The Zika virus (ZIKV), a member of the Flaviviridae family, has caused multiple widespread outbreaks, posing significant challenges to global health. This study explores the potential of compounds from Echinacea angustifolia ( E. angustifolia ) to inhibit the activity of ZIKV’s RNA-dependent RNA polymerase (RDRP), a key enzyme in the viral replication process and an ideal candidate for antiviral therapy. Utilizing computational techniques, we conducted a thorough virtual examination using the MTi-OpenScreen tool to identify potential RDRP inhibitors among E. angustifolia compounds. The top four compounds were further examined through re-docking procedures. To assess the robustness and effectiveness of these interactions, we performed molecular dynamics simulations along with calculations of the binding free energy and PCA analysis. This investigation highlighted four naturally occurring compounds, viz., Echinacoside, Rutin, Echinacin, and Cynaroside, demonstrating a notable affinity for binding to the allosteric site of ZIKV RDRP. These compounds showed strong hydrogen bond formation with crucial residues of the RDRP and presented favorable binding free energies. Our research sheds light on the viability of these E. angustifolia compounds as ZIKV RDRP inhibitors, laying a foundation for further experimental research in developing novel antiviral treatments against ZIKV infections.

Zika virus (ZIKV) has been characterized as one of many potential pathogens and placed under future epidemic outbreaks by the WHO. However, a lack of potential therapeutics can result in an uncontrolled pandemic as with other human pandemic viruses. Therefore, prioritized effective therapeutics development has been recommended against ZIKV. In this context, the present study adopted a strategy to explore the lead compounds from Azadirachta indica against ZIKV via concurrent inhibition of the NS2B-NS3 protease (ZIKVpro) and NS5 RNA dependent RNA polymerase (ZIKVRdRp) proteins using molecular simulations. Initially, structure-based virtual screening of 44 bioflavonoids reported in Azadirachta indica against the crystal structures of targeted ZIKV proteins resulted in the identification of the top four common bioflavonoids, viz. Rutin, Nicotiflorin, Isoquercitrin, and Hyperoside. These compounds showed substantial docking energy (−7.9 to −11.01 kcal/mol) and intermolecular interactions with essential residues of ZIKVpro (B:His51, B:Asp75, and B:Ser135) and ZIKVRdRp (Asp540, Ile799, and Asp665) by comparison to the reference compounds, O7N inhibitor (ZIKVpro) and Sofosbuvir inhibitor (ZIKVRdRp). Besides, long interval molecular dynamics simulation (500 ns) on the selected docked poses reveals stability of the respective docked poses contributed by intermolecular hydrogen bonds and hydrophobic interactions. The predicted complex stability was further supported by calculated end-point binding free energy using molecular mechanics generalized born surface area (MM/GBSA) method. Consequently, the identified common bioflavonoids are recommended as promising therapeutic inhibitors of ZIKVpro and ZIKVRdRp against ZIKV for further experimental assessment.

The Ebola virus and its close relative, the Marburg virus, both belong to the family Filoviridae and are highly hazardous and contagious viruses. With a mortality rate ranging from 23% to 90%, depending on the specific outbreak, the development of effective antiviral interventions is crucial for reducing fatalities and mitigating the impact of Marburg virus outbreaks. In this investigation, a virtual screening approach was employed to evaluate 2042 natural compounds for their potential interactions with the VP35 protein of the Marburg virus. Average and worst binding energies were calculated for all 20 poses, and compounds that exhibited binding energies <−6 kcal/mol in both criteria were selected for further analysis. Based on binding energies, only six compounds (Estradiol benzoate, INVEGA (paliperidone), Isosilybin, Protopanaxadiol, Permethrin, and Bufalin) were selected for subsequent investigations, focusing on interaction analysis. Among these selected compounds, Estradiol benzoate, INVEGA (paliperidone), and Isosilybin showed strong hydrogen bonds, while the others did not. In this study, the compounds Myricetin, Isosilybin, and Estradiol benzoate were subjected to a molecular dynamics (MD) simulation and free binding energy calculation using MM/GBSA analysis. The reference component Myricetin served as a control. Estradiol benzoate exhibited the most stable and consistent root-mean-square deviation (RMSD) values, whereas Isosilybin showed significant fluctuations in RMSD. The compound Estradiol benzoate exhibited the lowest ΔG binding free energy (−22.89 kcal/mol), surpassing the control compound’s binding energy (−9.29 kcal/mol). Overall, this investigation suggested that Estradiol benzoate possesses favorable binding free energies, indicating a potential inhibitory mechanism against the VP35 protein of the Marburg virus. The study proposes that these natural compounds could serve as a therapeutic option for preventing Marburg virus infection. However, experimental validation is required to further corroborate these findings.