Search Results (513)

The emergence of SARS-CoV-2 variants highlights the urgent need for novel therapeutic strategies, particularly entry inhibitors that could efficiently prevent viral infection. Medicinal herbs and herbal combination formulas have long been recognized for their effects in treating infectious diseases and their antiviral properties, thus providing abundant resources for the discovery of antiviral candidates. While many candidates have been suggested to have antiviral activity against SARS-CoV-2 infection, few have been validated for their mechanisms, including possible effects on viral entry. This study aimed to identify SARS-CoV-2 entry inhibitors from medicinal herbs and herbal formulas that are known for heat-clearing and detoxifying properties and/or antiviral activities. A SARS-CoV-2 pseudoparticle (SARS-CoV-2pp) system was used to assess mechanism-specific entry inhibition. Our results showed that the methanol extract of Anemarrhena asphodeloides rhizome, as well as the water extracts of Cimicifuga foetida rhizome, Xiao Chai Hu Tang (XCHT), and Sheng Ma Ge Gen Tang (SMGGT), have substantial inhibitory effects on the entry of SARS-CoV-2pps into host cells. Given the observation that Cimicifuga foetida exhibited the most potent inhibition and is a constituent of SMGGT, we further investigated the major compounds of the herb and identified caffeic acid as a bioactive component for blocking SARS-CoV-2pp entry. Entry inhibition of Cimicifuga foetida and caffeic acid was validated on both wild-type and the currently dominant JN.1 strain SARS-CoV-2pp systems. Moreover, caffeic acid was able to both inactivate the pseudoparticles and prevent their entry into pretreated host cells. The results support the traditional use of these herbal medicines and underscore their potential as valuable resources for identifying active compounds and developing therapeutic entry inhibitors for the management of COVID-19. Full article

This study is the first to investigate the performance of ultraviolet germicidal irradiation (UVGI) in underfloor air distribution (UFAD) systems. A simplified mathematical model is developed to predict airborne pathogen transport and inactivation by upper room UVGI in UFAD spaces. The proposed model is substantiated for the SARS-CoV-2 virus as a simulated pathogen through a comprehensive computational fluid dynamics methodology validated against published experimental data of upper room UVGI and UFAD flows. Simulations show an 11% decrease in viral concentration within the upper irradiated zone when a 15 W louvered germicidal lamp is utilized. Finally, a case study on Mycobacterium tuberculosis (M. tuberculosis) bacteria is carried out using the validated simplified model to optimize the use of return air and UVGI implementation, ensuring acceptable indoor air quality and enhanced energy efficiency. Results reveal that the UFAD-UVGI system may consume up to 13.6% less energy while keeping the occupants at acceptable levels of M. tuberculosis concentration and UV irradiance when operated with 26% return air and a UVGI output of 72 W. Full article

Background: Influenza A viruses (IAV) cause seasonal flu and occasional pandemics. In addition, the potential for the emergence of new strains presents unknown challenges for public health. Face masks and other personal protective equipment (PPE) can act as barriers that prevent the spread of these viruses. Metal ions embedded into PPE have been demonstrated to inactivate respiratory viruses, but the underlying mechanism of inactivation and potential for resistance is presently not well understood. Methods: In this study, we used hemagglutination assays to quantify the effect of zinc ions on IAV sialic acid receptor binding. We varied the zinc concentration, incubation time, incubation temperature, and passaged IAV in the presence of zinc ions to investigate if resistance to zinc ions could evolve. Results: We found that zinc ions impact the ability of IAV particles to hemagglutinate and observed inhibition within 1 min of exposure. Maximum inhibition was achieved within 1 h and sustained for at least 24 h in a concentration-dependent manner. Inhibition was also temperature-dependent, and optimal above room temperature. Serial passaging of IAV in the presence of zinc ions did not result in resistance. Conclusions: e conclude that zinc ions prevent IAV hemagglutination in a concentration and temperature-dependent manner for at least 24 h. Overall, these findings are in line with previous observations indicating that zinc-embedded materials can inactivate the IAV hemagglutinin and SARS-CoV-2 spike proteins, and they support work toward developing robust, passive, self-cleaning antiviral barriers in PPE. Full article

In recent years, the persistent emergence of novel infectious pathogens (epitomized by the global coronavirus disease-2019 (COVID-2019) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) has propelled nucleic acid testing (NAT) into an unprecedented phase of rapid development. As a key technology in modern molecular diagnostics, NAT achieves precise pathogen identification through specific nucleic acid sequence recognition, establishing itself as an indispensable diagnostic tool across diverse scenarios, including public health surveillance, clinical decision-making, and food safety control. The reliability of NAT systems fundamentally depends on reference materials (RMs) that authentically mimic the biological characteristics of natural viruses. This critical requirement reveals significant limitations of current RMs in the NAT area: naked nucleic acids lack the structural authenticity of viral particles and exhibit restricted applicability due to stability deficiencies, while inactivated viruses have biosafety risks and inter-batch heterogeneity. Notably, pseudovirus has emerged as a novel RM that integrates non-replicative viral vectors with target nucleic acid sequences. Demonstrating superior performance in mimicking authentic viral structure, biosafety, and stability compared to conventional RMs, the pseudovirus has garnered substantial attention. In this comprehensive review, we critically summarize the engineering strategies of pseudovirus platforms and their emerging role in ensuring the reliability of NAT systems. We also discuss future prospects for standardized pseudovirus RMs, addressing key challenges in scalability, stability, and clinical validation, aiming to provide guidance for optimizing pseudovirus design and practical implementation, thereby facilitating the continuous improvement and innovation of NAT technologies. Full article

The emergence of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus closely related to SARS-CoV and officially known as Betacoronavirus pandemicum precipitated a substantial surge in vaccine development that culminated during the global COVID-19 pandemic. At present, there are dozens of vaccines for the prevention of SARS-CoV-2 being utilized across the globe. However, only 10 of these vaccines have been authorized by the World Health Organization (WHO). These include mRNA-based, viral vector, subunit and whole-virion inactivated vaccines. At the current end of the pandemic, there has been a decline in the global vaccination rate, both for the general population and for those most at risk of severe illness from the virus. This suggests that the effectiveness of the vaccines may be waning. The decline occurs alongside a decrease in testing and sequencing for SARS-CoV-2. Furthermore, the process of tracking viruses becomes increasingly complex, thereby providing a selective advantage for SARS-CoV-2 and allowing it to evolve stealthily. In this review, we provide a comprehensive overview of viral evolution and vaccine development. We also discuss ways to overcome viral variability and test universal vaccines for all SARS-CoV-2 variants. Full article

Background: Starting in early 2022, SARS-CoV-2 Omicron has driven large outbreaks in China, a predominantly infection-naive population with high inactivated vaccine coverage. This unique context provided a substantially less-confounded opportunity to evaluate how vaccination, public health, and social measures influenced severity. Methods: We systematically reviewed 86 studies (224 severity estimates) published from 2022 to 2024, reporting symptom and clinical severity outcomes (fever, cough, and sore throat; symptomatic, severe/critical, and fatal illness) of Omicron infections in China. Using meta-regression, we evaluated the associations of study setting, age group, vaccination status, predominant subvariants, and Oxford COVID-19 Government Response Tracker (OxCGRT) indices, including the Government Response Index (GRI), Containment and Health Index (CHI), and the Stringency Index (SI), with infection outcomes, adjusting for key confounders. Results: We found the primary or booster series of inactivated vaccines conferred strong protection against severe/critical illness (pooled relative risk (RR) 0.17 [95% CI: 0.09–0.33]) but did not reduce symptom frequency (RR 0.99 [95% CI: 0.95–1.02]). Each 10-unit increase in GRI or CHI was associated with 7% (95% CI: 1–12%) and 6% (95% CI: 1–10%) lower odds of symptomatic infection and 3% (95% CI: 1–4%) lower odds of severe/critical illness. Later subvariants (BA.5, BF.7, and XBB) showed 24–38% higher odds of upper respiratory symptoms versus BA.1. Conclusions: The data collection context significantly impacted severity estimates, with higher estimates from emergency hospitals. Overall, inactivated vaccines provided strong protection against severe/critical outcomes while stringent public health measures were associated with lower severity. Our findings underscore the importance of consistent and standardized protocols to produce reliable estimates of SARS-CoV-2 severity in evolving epidemiological contexts. Full article

Patients undergoing peritoneal dialysis (PD) represent a uniquely vulnerable population due to intrinsic immunological dysfunction and a high prevalence of comorbid conditions. This review examines the complex interplay between natural and vaccine-induced immune responses to SARS-CoV-2 in this group, focusing on viral entry, immune activation, and immune evasion mechanisms. Particular attention is given to the impaired cellular and humoral responses seen in PD patients, including reduced T-cell function, diminished antibody production, and abnormal cytokine signaling, all of which contribute to an elevated risk of severe COVID-19 outcomes. The immunogenicity and clinical efficacy of various vaccine platforms, including inactivated, vector-based, and mRNA formulations, are critically assessed, with an emphasis on the role of booster doses in enhancing protection amid waning immunity and evolving viral variants. Furthermore, the review highlights the advantages of PD as a home-based modality that is compatible with telemedicine and may reduce the risk of viral exposure. These insights underscore the importance of developing individualized vaccination strategies, maintaining close immunological surveillance, and implementing innovative dialysis care approaches to improve clinical outcomes during the ongoing pandemic and future public health crises. Tailored booster strategies and telemedicine-integrated care models are essential for improving outcomes in this high-risk population. Full article

Background: Vaccines are crucial for preventing infectious diseases, as both humoral and cellular immune responses play a vital role in combating viral infections. The cellular immune response is crucial against SARS-CoV-2, particularly with the emergence of new variants that evade antibody neutralization. This study focuses on the immune memory response in individuals who have been vaccinated with the Sinopharm BBIBP-CorV vaccine. Methods: A cross-sectional study evaluated lymphocyte subpopulations using flow cytometry in 52 vaccinated adults (30 females, 22 males) who had been exposed to SARS-CoV-2 or diagnosed with COVID-19. Conducted from February to June 2023 during the Omicron variant’s circulation, this study assessed antigens—CD154 in CD4+ T cells, CD107 and CD314 in CD8+ T cells, CD314 in NK cells, and CD86 in CD19 B cells—after stimulation with viral peptides and an inactivated virus. Granzyme B and IFN-γ were quantified using ELISA. Results: The memory response, regardless of gender, age, or Body Mass Index (BMI), was mild but significant upon exposure to a viral antigen or inactivated virus. An increase in the secretion of IFN-γ and granzyme B was also observed. Conclusions: It is suggested that the vaccine was able to generate a mild long-term memory against the SARS-CoV-2 virus in vaccinated adult individuals, independent of gender and BMI. Full article

The COVID-19 pandemic has heightened awareness of airborne disease susceptibility, leading to the development and adoption of various preventive technologies. Among these, microwave sanitization, which inactivates virions through non-thermal mechanical resonance, has gained significant scientific credibility. Laboratory tests have demonstrated its high efficacy, prompting further investigation into its effectiveness in real-world settings. This study employs multi-physical, fluid-dynamic and electromagnetic simulations of office environments to evaluate the reduction of contagion risk. By integrating these simulations with virus inactivation experimental laboratory results, we observed that the introduction of a microwave sanitization device significantly reduces the risk of contamination among individuals in the same environment. These findings suggest potential applications and further studies in other everyday scenarios. Full article

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has plunged the world into a major crisis of overwhelming morbidity and mortality and emerged various mutant strains. Patients recovering from SARS-CoV-2 develop post-acute COVID syndrome, commonly known as long COVID (LC), lasting up to 12 weeks or even longer. The mechanism has yet to be clarified. COVID-19 pseudovirus is a suitable model to understand the infection of the COVID-19 virus to cells, which is suitable to see the acute change in cells owing to its one-time infection and inactivation. The ACE2-293T cell infected by COVID-19 pseudovirus was used in this study. After the infection and removal of the pseudovirus, high amounts of ferrous ions were accumulated in mitochondria and then released into the cytosol. Reactive oxygen species (ROS) accumulation was formed and caused mitochondrial dysfunction. To evaluate the effect of nutritional strategy on ferrous ion accumulation and mitochondrial dysfunction, lactoferrin, Q10 and Echinacea purpurea extract (EPE) were used in this study. Results showed that lactoferrin, Q10 and EPE could improve mitochondrial dysfunction by reducing the accumulation of ferrous ions and ROS in the mitochondria. HPLC analysis showed that EPE contained rich caffeic acid, and it also showed perfect improvement in mitochondrial dysfunction. In conclusion, cells infected with pseudovirus could increase the accumulation of ferrous ions and ROS in mitochondria and be released into the cytosol after removing pseudovirus, thereby causing mitochondrial dysfunction. Lactoferrin, Q10 and EPE were an effective nutritional strategy to suppress ferrous ion accumulation, ROS formation and advanced mitochondrial dysfunction. Full article

The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of variants of concern (VOCs) underscore the critical role of vaccination in pandemic control. These mutations not only enhance viral infectivity but also facilitate immune evasion and diminish vaccine efficacy, necessitating ongoing surveillance and vaccine adaptation. Current SARS-CoV-2 vaccines, including inactivated, live-attenuated, viral vector, protein subunit, virus-like particle, and nucleic acid vaccines, face challenges due to the immune evasion strategies of emerging variants. Moreover, other sarbecoviruses, such as SARS-CoV-1 and SARS-related coronaviruses (SARSr-CoVs) pose a potential risk for future outbreaks. Thus, developing vaccines capable of countering emerging SARS-CoV-2 variants and providing broad protection against multiple sarbecoviruses is imperative. Several innovative vaccine platforms are being investigated to elicit broad-spectrum neutralizing antibody responses, offering protection against both current SARS-CoV-2 variants and other sarbecoviruses. This review presents an updated overview of the key target antigens and therapeutic strategies employed in current SARS-CoV-2 vaccines. Additionally, we summarize ongoing approaches for the development of vaccines targeting infectious sarbecoviruses. Full article

Background/Objectives: Identification and characterization of broadly neutralizing monoclonal antibodies from individuals exposed to SARS-CoV-2, either by infection or vaccination, can inform the development of next-generation vaccines and antibody therapeutics with pan-SARS-CoV-2 protection. Methods: Through single B cell sorting and RT-PCR, monoclonal antibodies (mAbs) were isolated from a donor who experienced a BA.5 or BF.7 breakthrough infection after three doses of inactivated vaccines. Their binding and neutralizing capacities were measured with ELISA and a pseudovirus-based neutralization assay, respectively. Their epitopes were mapped by competition ELISA and site-directed mutation. Results: Among a total of 67 spike-specific mAbs cloned from the donor, four mAbs (KXD643, KXD652, KXD681, and KXD686) can neutralize all tested SARS-CoV-2 variants from wild-type to KP.3. Moreover, KXD643, KXD652, and KXD681 belong to a clonotype encoded by IGHV5-51 and IGKV1-13 and recognize the cryptic and conserved RBD-8 epitope on the receptor-binding domain (RBD). In contrast, KXD686 is encoded by IGHV1-69 and IGKV3-20 and targets a conserved epitope (NTD Site iv) outside the antigenic supersite (NTD Site i) of the N-terminal domain (NTD). Notably, antibody cocktails containing these two groups of mAbs can neutralize SARS-CoV-2 more potently due to synergistic effects. In addition, bispecific antibodies derived from KXD643 and KXD686 demonstrate further improved neutralizing potency compared to antibody cocktails. Conclusions: These four mAbs can be developed as candidates of pan-SARS-CoV-2 antibody therapeutics through further antibody engineering. On the other hand, vaccines designed to simultaneously elicit neutralizing antibodies towards RBD-8 and NTD Site iv have the potential to provide pan-SARS-CoV-2 protection. Full article

Over the past several decades, viral vector-based vaccines have emerged as some of the most versatile and potent platforms in modern vaccinology. Their capacity to deliver genetic material encoding target antigens directly into host cells enables strong cellular and humoral immune responses, often superior to what traditional inactivated or subunit vaccines can achieve. This has accelerated their application to a wide array of pathogens and disease targets, from well-established threats like HIV and malaria to emerging infections such as Ebola, Zika, and SARS-CoV-2. The COVID-19 pandemic further highlighted the agility of viral vector platforms, with several adenovirus-based vaccines quickly authorized and deployed on a global scale. Despite these advances, significant challenges remain. One major hurdle is pre-existing immunity against commonly used vector backbones, which can blunt vaccine immunogenicity. Rare but serious adverse events, including vector-associated inflammatory responses and conditions like vaccine-induced immune thrombotic thrombocytopenia (VITT), have raised important safety considerations. Additionally, scaling up manufacturing, ensuring consistency in large-scale production, meeting rigorous regulatory standards, and maintaining equitable global access to these vaccines present profound logistical and ethical dilemmas. In response to these challenges, the field is evolving rapidly. Sophisticated engineering strategies, such as integrase-defective lentiviral vectors, insect-specific flaviviruses, chimeric capsids to evade neutralizing antibodies, and plug-and-play self-amplifying RNA approaches, seek to bolster safety, enhance immunogenicity, circumvent pre-existing immunity, and streamline production. Lessons learned from the COVID-19 pandemic and prior outbreaks are guiding the development of platform-based approaches designed for rapid deployment during future public health emergencies. This review provides an exhaustive, in-depth examination of the historical evolution, immunobiological principles, current platforms, manufacturing complexities, regulatory frameworks, known safety issues, and future directions for viral vector-based vaccines. Full article

Background/Objectives: The antibody-dependent enhancement (ADE) of viral entry has been documented for SARS-CoV-2 infection both in vitro and in vivo. However, the potential for the SARS-CoV-2 vaccination to elicit similar ADE effects remains unclear. Methods: In this study, we assessed the in vitro ADE potential of monoclonal antibodies (mAbs) derived from individuals vaccinated with the inactivated SARS-CoV-2 vaccine and compared them to those from one convalescent donor. Results: Our analysis revealed no significant difference in binding affinity or neutralizing capacity between the vaccinated and convalescent mAbs. However, the inactivated SARS-CoV-2 vaccination induced fewer ADE-inducing mAbs, particularly those targeting the Class III epitope on the receptor-binding domain (RBD) compared to those from the convalescent individual. Moreover, no significant in vitro ADE was detected in either vaccinated or convalescent sera, indicating low levels of ADE-inducing antibodies in the sera. Conclusions: An inactivated SARS-CoV-2 vaccination induces fewer ADE-inducing antibodies compared to natural infection, further emphasizing the safety of inactivated SARS-CoV-2 vaccines. Full article

Background: COVID-19, caused by SARS-CoV-2, poses a significant threat to human health. Vaccines designed for T-cell epitopes play an important role in eliminating the virus. However, T cell epitope screening often requires the use of a large number of peripheral blood mononuclear cells (PBMCs) from infected or convalescent patients, and if MHC humanized mice can be used for epitope screening, they will not have to wait for enough PBMCs to be available to screen for epitopes, thus buying time for epitope confirmation and vaccine design. Methods: In this study, we used SARS-CoV-2 BA.5 to infect HLA-A11/DR1, C57BL/6, hACE2 mice, and detected body weight changes, viral load, and pathological changes after infection. Fourteen days after the HLA-A11/DR1 and C57BL/6 mice were immunized against inactivated viruses, IgG antibodies were detected in mouse serum using ELISA, and IFN-γ produced by peptide stimulation of splenocytes was detected by ELISpot. Results: There is no obvious pathogenic phenotype of SARS-CoV-2 infection in HLA-A11/DR1 mice. Specific IgG antibodies were detected in serum after immunization of inactivated virus in both HLA-A11/DR1 and C57BL/6 mice, but specific IFN-γ was detected in splenocytes of HLA-A11/DR1 mice. Conclusions: Although HLA-A11/DR1 mice are unable to replicate the virus effectively in vivo, they are able to generate cellular immune responses after immunization inactivated viruses. Therefore, it can be used as a tool to substitute for human PBMCs in epitope screening, thus shortening the timeliness of T cell epitope screening and obtaining the immunogenicity information of new epitopes in a timely manner. Full article