Severe acute respiratory syndrome coronavirus 2 non-structural protein 8 (SARS-CoV-2 nsp8) is a multifunctional protein essential for viral replication and immune evasion. However, the host factors that regulate nsp8 stability and function remain unclear. In this study, we identify HECT and RCC-like domain-containing protein 5 (HERC5) as an essential E3 ligase that regulates nsp8 stability through ISGylation, a ubiquitin-like post-translational modification that facilitates proteasome-dependent degradation. HERC5 overexpression significantly enhances nsp8 degradation in an enzymatic activity-dependent manner, whereas SARS-CoV-2 papain-like protease (PLpro) counteracts this process by deconjugating interferon-stimulated gene 15 (ISG15) from nsp8-thereby preventing its degradation and facilitating viral replication. Mass spectrometry and mutational analyses revealed that the N2 domain of nsp8 is indispensable for ISGylation, with multiple lysine residues acting as primary modification sites. Additionally, we demonstrated that the ISGylation system, including HERC5, ubiquitin-like modifier activating enzyme 7 (UBA7), and ISG15, effectively suppresses SARS-CoV-2 replication across multiple variants, including Omicron BA.5 and XBB.1.5.15. These findings provide novel insights into the role of ISGylation in host antiviral defense and highlight the interplay between HERC5 and PLpro in modulating viral replication. This study establishes a foundation for developing therapeutic strategies targeting HERC5 or PLpro to inhibit SARS-CoV-2 replication.

Background: SARS-CoV-2 is a positive-sense single-stranded RNA virus that has a propensity for infecting epithelial cells and the respiratory system. The two important proteins, structural and nonstructural proteins, make the architecture of this virus. Aim: This research aimed at studying significant mutations in spike protein of SARS-CoV-2 variants of concern (VoCs) and finding shared mutations among omicron and other four variants (alpha, beta, gamma, and delta). The purpose of this study was to draw structural comparisons between wild type and mutant proteins, followed by identifying potent inhibitors (ligand) that could be used against SARS-CoV-2 spike protein and its latest omicron VoC. Methodology: In this research, we had studied 16 major mutations as well as shared mutations (6) present in spike region of SARS-CoV-2. Subsequently, we determined the structure of the wild-type SARS-CoV-2 protein from the Protein Data Bank (PDB) with the ID 7R4I. Furthermore, the structure of the mutant protein of SARS-CoV-2 omicron variant was modeled in SWISS-MODEL. The ligand dataset for spike protein of SARS-CoV-2 was also collected from literature and different databases. Both wild type and mutant proteins were docked with ligand database in Molecular Operating Environment (MOE). The docking analysis was performed, and two best ligand molecules, AZ_2 and AZ_13, were finalized based on their energy values, interactions, and docking scores to be used against our wild and mutant proteins. Results: AZ_2 demonstrated a docking score of -6.1753 in MOE, with energy values of -4.3889 and -6.1753. It formed key hydrogen bond interactions. AZ_13 showed a docking score of -5.9, with energy values of -9.3 and -5.9, forming hydrogen donor and acceptor interactions with Asp950 (3.06 Å), Ile312 (3.13 Å), and Glu309 (3.27 Å). These interactions suggest strong binding affinity and potential efficacy. Thus, present research work emphasized on identification of significant mutations and finding a potent target-based drug against SARS-CoV-2 and its omicron variant. Outcomes: Based on this computational analysis performed, it is suggested that proposed compound can be used as remedy against SARS-CoV-2 and its omicron variant.

Kaposi's sarcoma-associated herpesvirus (KSHV), a member of the human γ-herpesviruses family, exhibits extensive cellular tropism and is associated with Kaposi's sarcoma and various B-cell malignancies. Despite its clinical significance, no effective prophylactic vaccines or specific therapeutics are currently available to prevent or treat KSHV infection. Similar to other herpesviruses, KSHV depends on the envelope glycoprotein B (gB) for host receptor recognition and membrane fusion initiation, making gB a prime target for antiviral antibody or vaccine development. In this study, the high-resolution cryo-electron microscopy (cryo-EM) structure of KSHV gB is presented, revealing a unique trimeric conformation resembling the postfusion state observed in other herpesviruses. Additionally, the structure of the non-neutralizing monoclonal antibody 2C4 bound to KSHV gB domain IV is resolved. The comparative sequence and structure analyses reveal significant homology in neutralizing epitopes between KSHV and Epstein-Barr virus (EBV) gB, indicating a potential pathway for the development of broad-spectrum antiviral strategies. These findings provide a foundation for a deeper understanding of KSHV's infectious mechanism and pave the way for the creation of universal interventions against the human γ-herpesviruses.

The SARS-CoV-2 Omicron variants show different behavior compared to the previous variants, especially with respect to the Delta variant, which promotes a lower morbidity despite being much more contagious. In this perspective, we performed molecular dynamics (MD) simulations of the different spike RBD/hACE2 complexes corresponding to the WT, Delta and four Omicron variants. Carrying out a comprehensive analysis of residue interactions within and between the two partners allowed us to draw the profile of each variant by using complementary methods (PairInt, hydrophobic potential, contact PCA). PairInt calculations highlighted the residues most involved in electrostatic interactions, which make a strong contribution to the binding with highly stable interactions between spike RBD and hACE2. Apolar contacts made a substantial and complementary contribution in Omicron with the detection of two hydrophobic patches. Contact networks and cross-correlation matrices were able to detect subtle changes at point mutations as the S375F mutation occurring in all Omicron variants, which is likely to confer an advantage in binding stability. This study brings new highlights on the dynamic binding of spike RBD to hACE2, which may explain the final persistence of Omicron over Delta.

The evolution of SARS-CoV-2 pathogenicity has been a major focus of attention. However, the determinants of pathogenicity are still unclear. Various hypotheses have attempted to elucidate the mechanisms underlying the evolution of viral pathogenicity, but a definitive conclusion has yet to be reached. Here, we review the potential impact of all proteins in SARS-CoV-2 on the viral pathogenic process and analyze the effects of their mutations on pathogenicity evolution. We aim to summarize which virus-encoded proteins are crucial in influencing viral pathogenicity, defined as disease severity following infection. Mutations in these key proteins, which are the virulence factors in SARS-CoV-2, may be the driving forces behind the evolution of viral pathogenicity. Mutations in the S protein can impact viral entry and fusogenicity. Mutations in proteins such as NSP2, NSP5, NSP14, and ORF7a can alter the virus's ability to suppress host protein synthesis and innate immunity. Mutations in NSP3, NSP4, NSP6, N protein, NSP5, and NSP12 may alter viral replication efficiency. The combined effects of mutations in the S protein and NSP6 can significantly reduce viral replication. In addition, various viral proteins, including ORF3a, ORF8, NSP4, Spike protein, N protein, and E protein, directly participate in the inflammatory process. Mutations in these proteins can modulate the levels of inflammation following infection. Collectively, these viral protein mutations can influence SARS-CoV-2 pathogenicity by impacting viral immune evasion, replication capacity, and the level of inflammation mediated by infection. In conclusion, the evolution of SARS-CoV-2 pathogenicity is likely determined by multiple virulence factors.

To analyze the epidemiological characteristics of the SARS-CoV-2 infection and reinfection associated with the emergence of Omicron variant in Healthcare workers (HCWs).

We enrolled 760 HCWs who received 2-4 vaccination doses of COVID-19 and followed by BA.5/BF.7 and/or XBB.1.5 breakthrough infections between December 2022 and July 2023. Serum sample from each individual were collected approximately 1,3 and 6 months after last exposure. IgM, IgG and Total antibodies against SARS-CoV-2 were measured by chemiluminescent immunoassay. Meanwhile, we created an Enterprise WeChat link for HCWs to self-report SARS-CoV-2 infections, symptoms and post COVID-19 conditions.

Our study revealed that the reinfection rate among HCWs reached 26.1%. The main symptoms were fever (91.2% vs 60.1%), cough (78.8% vs 58.0%), and sore throat (75.4% vs 59.6%) during infection and reinfection in Omicron BA.5/BF.7 and XBB.1.5 wave, and the interval for reinfection ranged from 91 to 210 days (median 152). Fatigue (23.6%), memory loss (18.8%) and coughing (18.6%) were the most prevalent long COVID symptoms, with a higher prevalence among female HCWs.

HCWs reinfection with SARS-CoV-2 causes milder symptoms, but high reinfection rate and short intervals. Strengthen infection prevention and control is crucial to mitigating infection risk and improving health services.

We studied severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination status among six ethnic groups in Amsterdam, the Netherlands. We analysed participants of the Healthy Life in an Urban Setting cohort who were tested for SARS-CoV-2 spike protein antibodies between 17 May and 21 November 2022. We categorized participants with antibodies as only infected, only vaccinated (≥1 dose), or both infected and vaccinated, based on self-reported prior infection and vaccination status and previous seroprevalence data. We compared infection and vaccination status between ethnic groups using multivariable, multinomial logistic regression. Of the 1,482 included participants, 98.5% had SARS-CoV-2 antibodies (P between ethnic groups = 0.899). Being previously infected and vaccinated ranged from 41.5% (95% confidence interval (CI) = 35.0-47.9%) in the African Surinamese to 67.1% (95% CI = 59.1-75.0%) in the Turkish group. Compared to participants of Dutch origin, participants of South-Asian Surinamese (adjusted odds ratio (aOR) = 3.31, 95% CI = 1.50-7.31)), African Surinamese (aOR = 10.41, 95% CI = 5.17-20.94), Turkish (aOR = 3.74, 95% CI = 1.52-9.20), or Moroccan (aOR = 15.24, 95% CI = 6.70-34.65) origin were more likely to be only infected than infected and vaccinated, after adjusting for age, sex, household size, trust in the government's response to the pandemic, and month of study visit. SARS-CoV-2 infection and vaccination status varied across ethnic groups, particularly regarding non-vaccination. As hybrid immunity is most protective against coronavirus disease 2019, future vaccination campaigns should encourage vaccination uptake in specific demographic groups with only infection.

The viral protein mutations can modify virus-host interactions during virus evolution, and thus alter the extent of infection or pathogenicity. Studies indicate that nucleocapsid (N) protein of SARS-CoV-2 participates in viral genome assembly, intracellular signal regulation and immune interference. However, its biological function in viral evolution is not well understood. SARS-CoV-2 N protein mutations were analyzed in Delta, Omicron, and original strains. Two mutations with a methionine (M) residue at site 203 and a tyrosine (Y) residue at site 377 of the N protein were found in Delta strain but not in Omicron and original strains, and promoted SARS-CoV-2 infection therein. Those mutations, R203M and D377Y, enhanced the inhibitory impact of N protein on the impairment of RIG-I-mediated antiviral signaling, such as IRF3 phosphorylation and IFN-β activation. The viral RNA-binding activity of N protein was promoted by these mutations, effectively attenuating the recognition and interaction of RIG-I with viral RNA compared to the original or other variants. The R203M/D377Y mutations thus enhanced the suppressive activity of the N protein on RIG-I-mediated interferon induction both in vitro and in vivo, which in turn promoted viral replication. This study helps to understand the variability of SARS-CoV-2 in regulating host immunity.

The GENCOV study sought to evaluate serological differences between individuals with differing COVID-19 severity and outcomes. We assessed the SARS-CoV-2 antibody response of GENCOV participants cross-sectionally 1-, 6-, and 12-months following COVID-19 diagnosis to identify patient factors associated with more robust and durable humoral immune responses.

COVID-19 patients and a control cohort of vaccinated infection-naïve participants were recruited at hospital sites across the Greater Toronto Area in Ontario, Canada. Commercially available and laboratory-developed serological assays were used to characterize features of participants' antibody responses, including both binding and neutralizing antibodies. Regression analyses were performed to identify associations between participant characteristics and features of the SARS-CoV-2 antibody response.

Samples were obtained from participants 1- (n = 938), 6- (n = 842), and 12-months (n = 662) post-infection or vaccination. At all time points, vaccinees, and to a greater extent those who were both infected and vaccinated, had significantly elevated anti-spike antibody levels compared to unvaccinated participants. Increasing age and/or illness severity were associated with significantly higher antibody levels among unvaccinated participants. Among vaccines, those who were vaccinated after infection (i.e., hybrid immunity) had consistently higher antibody levels compared to participants who were infection-naïve or vaccinated before their infection (i.e., breakthrough infections). Additionally, receiving more vaccine doses and having a more recent vaccination were strongly associated with higher antibody levels across all time points.

Our findings highlight various patient factors, including vaccination, which contribute to robust, durable SARS-CoV-2 antibody responses. Overall, the findings presented here may inform future vaccine development and rollout plans.

Astroviruses (AstVs) are notable for their propensity for cross-species transmission; however, the molecular determinants underlying this phenomenon remain poorly understood. The spike protein, which is responsible for host cell entry and is a major antigenic determinant, is hypothesized to play a pivotal role. In this study, we observed high sequence variability in the spike region of AstV. Structural analyses have revealed variability, arising from diverse evolutionary relationships, among AstVs of the same host origin. AstV spike proteins can be categorized into six groups, each of which encompasses AstVs from diverse hosts that exhibit high degrees of structural similarity. These six groups correspond to branches observed in the phylogenetic tree. Notably, the spike surface-exposed loops emerged as focal hotspots for B-cell epitopes across groups, with sequence variability that may contribute to immune evasion upon host switching. Differences in the spike structures of AstVs infecting the same host raise the possibility of distinct tissue tropisms and corresponding clinical manifestations. Collectively, our findings provide insights into the roles of spike protein similarities and immune epitope diversity in driving AstV cross-species transmission. Understanding these molecular mechanisms is crucial to predicting and mitigating the emergence of novel AstV strains.

Even though COVID-19 is no longer the primary focus of the global scientific community, its high mutation rate (nearly 30 substitutions per year) poses a threat of a potential comeback. Effective vaccines have been developed and administered to the population, ending the pandemic. Nonetheless, reinfection by newly emerging subvariants, particularly the latest JN.1 strain, remains common. The rapid mutation of this virus demands a fast response from the scientific community in case of an emergency. While the immune escape of earlier variants was extensively investigated, one still needs a comprehensive understanding of how specific mutations, especially in the newest subvariants, influence the antigenic escape of the pathogen. Here, we tested comprehensive in silico approaches to identify methods for fast and accurate prediction of antibody neutralization by various mutants. As a benchmark, we modeled the complexes of the murine antibody 2B04, which neutralizes infection by preventing the SARS-CoV-2 spike glycoprotein's association with angiotensin-converting enzyme (ACE2). Complexes with the wild-type, B.1.1.7 Alpha, and B.1.427/429 Epsilon SARS-CoV-2 variants were used as positive controls, while complexes with the B.1.351 Beta, P.1 Gamma, B.1.617.2 Delta, B.1.617.1 Kappa, BA.1 Omicron, and the newest JN.1 Omicron variants were used as decoys. Three essentially different algorithms were employed: forced placement based on a template, followed by two steps of extended molecular dynamics simulations; protein-protein docking utilizing PIPER (an FFT-based method extended for use with pairwise interaction potentials); and the AlphaFold 3.0 model for complex structure prediction. Homology modeling was used to assess the 3D structure of the newly emerged JN.1 Omicron subvariant, whose crystallographic structure is not yet available in the Protein Database. After a careful comparison of these three approaches, we were able to identify the pros and cons of each method. Protein-protein docking yielded two false-positive results, while manual placement reinforced by molecular dynamics produced one false positive and one false negative. In contrast, AlphaFold resulted in only one doubtful result and a higher overall accuracy-to-time ratio. The reasons for inaccuracies and potential pitfalls of various approaches are carefully explained. In addition to a comparative analysis of methods, some mechanisms of immune escape are elucidated herein. This provides a critical foundation for improving the predictive accuracy of vaccine efficacy against new viral subvariants, introducing accurate methodologies, and pinpointing potential challenges.

The evolution of SARS-CoV-2, which limits public control and treatment, seems to have occurred through multiple mechanisms, including recombination of cocirculating strains in hosts. However, insufficient experimental data have been obtained after coinfection. Therefore, we investigated the emergence of variants after coinfection with parental SARS-CoV-2 and the SARS-CoV-2 Delta. We found that fewer (approximately 50%) mutations accumulated in Calu-3 cells than in other cells after serial passaging. Previously, we established a long-term replication mouse model by infecting Calu-3 cell-derived xenograft tumors with SARS-CoV-2. Here, we utilized our model to investigate the outcome after coinfection. More diverse viral mutations, along with multiple high-frequency simultaneous mutations, were discovered in the tumors than during cell passaging. Viral isolates from the tumors showed no cytopathic effects and formed much smaller plaques. Phylogenetic analysis suggested that the genetic makeup of the variants remained largely the same as that of parental SARS-CoV-2 rather than the SARS-CoV-2 Delta. Viral challenge revealed that the isolates were less lethal than the parental SARS-CoV-2 and SARS-CoV-2 Delta strains. These findings suggest that parental SARS-CoV-2 predominates over the SARS-CoV-2 Delta when coinfected, but the SARS-CoV-2 Delta contributes to the evolution of parental SARS-CoV-2 variants toward better host adaptation without recombination.

Patients present a wide range of clinical severities in response severe acute respiratory syndrome coronavirus 2 infection, but the underlying molecular and cellular reasons why clinical outcomes vary so greatly within the population remains unknown. Here, we report that negative clinical outcomes in severely ill patients were associated with divergent RNA transcriptome profiles in peripheral immune cells compared with mild cases during the first weeks after disease onset. Protein-protein interaction analysis indicated that early-responding cytotoxic natural killer cells were associated with an effective clearance of the virus and a less severe outcome. This innate immune response was associated with the activation of select cytokine-cytokine receptor pathways and robust Th1/Th2 cell differentiation profiles. In contrast, severely ill patients exhibited a dysregulation between innate and adaptive responses affiliated with divergent Th1/Th2 profiles and negative outcomes. This knowledge forms the basis of clinical triage that may be used to preemptively detect high-risk patients before life-threatening outcomes ensue.

Determination of SARS-CoV-2 variant is significant to prevent the spreads of COVID-19 disease.

We aimed to evaluate the variants of SARS-CoV-2 rate in positive patients in Kanuni Sultan Suleyman Training and Research Hospital (KSS-TRH), Istanbul, Türkiye between 1st January and 30th November 2021 by using RT-PCR method.

Herein, 825,169 patients were evaluated (male:58.53% and female:41.47%) whether COVID-19 positive or not [( +):21.3% and (-):78.7%] and 175,367 patient was described as positive (53.2%-female and 46.8%-male) by RT-PCR. COVID-19 positive rate is observed highest in the 6-15- and 66-75-year age range. The frequencies were obtained as SARS-CoV-2 positive (without mutation of B.1.1.7 [B.1.1.7 (U.K), E484K, L452R, B.1.351 (S. Africa/Brazil) spike mutations] as 66.1% (n: 115,899), B.1.1.7 Variant as 23.2% (n:40,686), Delta mutation (L452R) variant as 9.8% (n:17,182), B.1.351 variant as 0.8% (n:1370) and E484K as 0.1% (n: 230). In April 2021, general SARS-CoV-2 and B.1.1.7 variant were dominantly observed. Up to July 2021, B.1.617.2 (Delta variant/ Indian variant) and E484K has been not observed. B.1.351 variant of SARS-CoV-2 has been started in February 2021 at the rarest ratio and March 2021 is the top point. September 2021 is the pick point of E484K. African/Brazil variant of SARS-CoV-2 has been started in February 2021 at the rarest ratio and March 2021 is the top point. September 2021 is the pick point of E484K. When the gender type is compared within the variants, women were found to be more prevalent in all varieties.

The meaning of these mutations is very important to understand the transmission capacity of the COVID-19 disease, pandemic episode, and diagnosis of the virus with mutation types. Understanding the variant type is important for monitoring herd immunity and the spread of the disease.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), emerged as a global outbreak in 2019, profoundly affecting both human health and the global economy. Various vaccine modalities were developed and commercialized to overcome this challenge, including inactivated vaccines, mRNA vaccines, adenovirus vector-based vaccines, and subunit vaccines. While intramuscular vaccines induce high IgG levels, they often fail to stimulate significant mucosal immunity in the respiratory system. We employed the Newcastle disease virus (NDV) vector expressing the spike protein of the SARS-CoV-2 Beta variant (rK148/beta-S), and evaluated the efficacy of intranasal vaccination with rK148/beta-S in K18-hACE2 transgenic mice. Intranasal vaccination with a low dose (106.0 EID50) resulted in an 86% survival rate after challenge with the SARS-CoV-2 Beta variant. Administration at a high dose (107.0 EID50) led to a reduction in lung viral load and 100% survival against the SARS-CoV-2 Beta and Delta variants. A high level of the SARS-CoV-2 spike-specific IgA was also induced in vaccinated mice lungs following the SARS-CoV-2 challenge. Our findings suggest that rK148/beta-S holds promise as an intranasal vaccine candidate that effectively induces mucosal immunity against SARS-CoV-2.

The emergence and ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the need for rapid vaccine development platforms that can be updated to counteract emerging variants of currently circulating and future emerging coronaviruses. Here we report the development of a "train model" subunit vaccine platform that contains a SARS-CoV-2 Wuhan S1 protein (the "engine") linked to a series of flexible receptor binding domains (RBDs; the "cars") derived from SARS-CoV-2 variants of concern (VOCs). We demonstrate that these linked subunit vaccines when combined with Sepivac SWE™, a squalene in water emulsion (SWE) adjuvant, are immunogenic in Syrian hamsters and subsequently provide protection from infection with SARS-CoV-2 VOCs Omicron (BA.1), Delta, and Beta. Importantly, the bivalent and trivalent vaccine candidates offered protection against some heterologous SARS-CoV-2 VOCs that were not included in the vaccine design, demonstrating the potential for broad protection against a range of different VOCs. Furthermore, these formulated vaccine candidates were stable at 2-8 °C for up to 13 months post-formulation, highlighting their utility in low-resource settings. Indeed, our vaccine platform will enable the development of safe and broadly protective vaccines against emerging betacoronaviruses that pose a significant health risk for humans and agricultural animals.

Development of potent and broad-spectrum drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains one of the top priorities, especially in the cases of the emergence of mutant viruses and inability of current vaccines to prevent viral transmission. In this study, we have generated a novel membrane fusion-inhibitory lipopeptide IPB29, which is currently under clinical trials; herein, we report its design strategy and preclinical data. First, we surprisingly found that IPB29 with a rigid linker between the peptide sequence and lipid molecule had greatly improved α-helical structure and antiviral activity. Second, IPB29 potently inhibited a large panel of SARS-CoV-2 variants including the previously and currently circulating viruses, such as Omicron XBB.5.1 and EG.5.1. Third, IPB29 could also cross-neutralize the bat- and pangolin-isolated SARS-CoV-2-related CoVs (RatG13, PCoV-GD, and PCoV-GX) and other human CoVs (SARS-CoV, MERS-CoV, HCoV-NL63, and HCoV-229E). Fourth, IPB29 administrated as an inhalation solution (IPB29-IS) in Syrian hamsters exhibited high therapeutic and preventive efficacies against SARS-CoV-2 Delta or Omicron variant. Fifth, the pharmacokinetic profiles and safety pharmacology of IPB29-IS were extensively characterized, providing data to support its evaluation in humans. In conclusion, our studies have demonstrated a novel design strategy for viral fusion inhibitors and offered an ideal drug candidate against SARS-CoV-2 and other coronaviruses.

The emergence and rapid spread of SARS-CoV-2 prompted the global community to identify innovative approaches to diagnose infection and sequence the viral genome because at several points in the pandemic positive case numbers exceeded the laboratory capacity to characterize sufficient samples to adequately respond to the spread of emerging variants. From week 10, 2020, to week 13, 2023, Slovenian routine complete genome sequencing (CGS) surveillance network yielded 41 537 complete genomes and revealed a typical molecular epidemiology with early lineages gradually being replaced by Alpha, Delta, and finally Omicron. We developed a targeted next-generation sequencing based variant surveillance strategy dubbed Spike Screen through sample pooling and selective SARS-CoV-2 spike gene amplification in conjunction with CGS of individual cases to increase throughput and cost-effectiveness. Spike Screen identifies variant of concern (VOC) and variant of interest (VOI) signature mutations, analyses their frequencies in sample pools, and calculates the number of VOCs/VOIs at the population level. The strategy was successfully applied for detection of specific VOC/VOI mutations prior to their confirmation by CGS. Spike Screen complemented CGS efforts with an additional 22 897 samples sequenced in two time periods: between week 42, 2020, and week 24, 2021, and between week 37, 2021, and week 2, 2022. The results showed that Spike Screen can be applied to monitor VOC/VOI mutations among large volumes of samples in settings with limited sequencing capacity through reliable and rapid detection of novel variants at the population level and can serve as a basis for public health policy planning.

Antigenic cartography is a tool for interpreting and visualizing antigenic differences between virus variants based on virus neutralization data. This approach has been successfully used in the selection of influenza vaccine seed strains. With the emergence of SARS-CoV-2 variants escaping vaccine-induced antibody response, adjusting COVID-19 vaccines has become essential. This review provides information on the antigenic differences between SARS-CoV-2 variants revealed by antigenic cartography and explores a potential of antigenic cartography-based methods (e.g., building antibody landscapes and neutralization breadth gain plots) for the quantitative assessment of the breadth of the antibody response. Understanding the antigenic differences of SARS-CoV-2 and the possibilities of the formed humoral immunity aids in the prompt modification of preventative vaccines against COVID-19.

The worldwide spread of SARS-CoV-2 has led to a significant economic and social burden on a global scale. Even though the pandemic has concluded, apprehension remains regarding the emergence of highly transmissible variants capable of evading immunity induced by either vaccination or prior infection. The success of viral penetration is due to the specific amino acid residues of the receptor-binding motif (RBM) involved in viral attachment. This region interacts with the cellular receptor ACE2, triggering a neutralizing antibody (nAb) response. In this study, we evaluated serum immunogenicity from individuals who received either a single dose or a combination of different vaccines against the original SARS-CoV-2 strain and a mutated linear RBM. Despite a modest antibody response to wild-type SARS-CoV-2 RBM, the Omicron variants exhibit four mutations in the RBM (S477N, T478K, E484A, and F486V) that result in even lower antibody titers. The primary immune responses observed were directed toward IgA and IgG. While nAbs typically target the RBD, our investigation has unveiled reduced seroreactivity within the RBD's crucial subregion, the RBM. This deficiency may have implications for the generation of protective nAbs. An evaluation of S1WT and S2WT RBM peptides binding to nAbs using microscale thermophoresis revealed a higher affinity (35 nM) for the S2WT sequence (GSTPCNGVEGFNCYF), which includes the FNCY patch. Our findings suggest that the linear RBM of SARS-CoV-2 is not an immunodominant region in vaccinated individuals. Comprehending the intricate dynamics of the humoral response, its interplay with viral evolution, and host genetics is crucial for formulating effective vaccination strategies, targeting not only SARS-CoV-2 but also anticipating potential future coronaviruses.

COVID-19 is a complex disease that can lead to fatal respiratory failure with extrapulmonary complications, either as a direct result of viral invasion in multiple organs or secondary to oxygen supply shortage. Liver is susceptible to many viral pathogens, and due to its versatile functions in the body, it is of great interest to determine how hepatocytes may interact with SARS-CoV-2 in COVID-19 patients. Liver injury is a major cause of death, and SARS-CoV-2 is suspected to contribute significantly to hepatopathy. Owing to the lack of knowledge in this field, further research is required to address these ambiguities. Therefore, we aimed to provide a comprehensive insight into host-virus interactions, underlying mechanisms, and associated risk factors by collecting results from epidemiological analyses and relevant laboratory experiments. Backed by an avalanche of recent studies, our findings support that liver injury is a sequela of severe COVID-19, and certain pre-existing liver conditions can also intensify the morbidity of SARS-CoV-2 infection in synergy. Notably, age, sex, lifestyle, dietary habits, coinfection, and particular drug regimens play a decisive role in the final outcome and prognosis as well. Taken together, our goal was to unravel these complexities concerning the development of novel diagnostic, prophylactic, and therapeutic approaches with a focus on prioritizing high-risk groups.

Patients with coronavirus disease-2019 (COVID-19) are characterized by hyperinflammation. Calprotectin (S100A8/S100A9) is a calcium- and zinc-binding protein mainly secreted by neutrophilic granulocytes or macrophages and has been suggested to be correlated with the severity and prognosis of COVID-19.

To thoroughly evaluate the diagnostic and prognostic utility of calprotectin in patients with COVID-19 by analyzing relevant studies.

PubMed, Web of Science, and Cochrane Library were comprehensively searched from inception to August 1, 2023 to retrieve studies about the application of calprotectin in COVID-19. Useful data such as the level of calprotectin in different groups and the diagnostic efficacy of this biomarker for severe COVID-19 were extracted and aggregated by using Stata 16.0 software.

Fifteen studies were brought into this meta-analysis. First, the pooled standardized mean differences (SMDs) were used to estimate the differences in the levels of circulating calprotectin between patients with severe and non-severe COVID-19. The results showed an overall estimate of 1.84 (95% confidence interval [CI]: 1.09-2.60). Diagnostic information was extracted from 11 studies, and the pooled sensitivity and specificity of calprotectin for diagnosing severe COVID-19 were 0.75 (95% CI: 0.64-0.84) and 0.88 (95% CI: 0.79-0.94), respectively. The AUC was 0.89 and the pooled DOR was 18.44 (95% CI: 9.07-37.51). Furthermore, there was a strong correlation between elevated levels of circulating calprotectin and a higher risk of mortality outcomes in COVID-19 patients (odds ratio: 8.60, 95% CI: 2.17-34.12; p < 0.1).

This meta-analysis showed that calprotectin was elevated in patients with severe COVID-19, and this atypical inflammatory cytokine might serve as a useful biomarker to distinguish the severity of COVID-19 and predict the prognosis.

Coronavirus disease 2019 (COVID-19), which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a global pandemic. The Omicron variant (B.1.1.529) was first discovered in November 2021 in specimens collected from Botswana, South Africa. Omicron has become the dominant variant worldwide, and several sublineages or subvariants have been identified recently. Compared to those of other mutants, the Omicron variant has the most highly expressed amino acid mutations, with almost 60 mutations throughout the genome, most of which are in the spike (S) protein, especially in the receptor-binding domain (RBD). These mutations increase the binding affinity of Omicron variants for the ACE2 receptor, and Omicron variants may also lead to immune escape. Despite causing milder symptoms, epidemiological evidence suggests that Omicron variants have exceptionally higher transmissibility, higher rates of reinfection and greater spread than the prototype strain as well as other preceding variants. Additionally, overwhelming amounts of data suggest that the levels of specific neutralization antibodies against Omicron variants decrease in most vaccinated populations, although CD4+ and CD8+ T-cell responses are maintained. Therefore, the mechanisms underlying Omicron variant evasion are still unclear. In this review, we surveyed the current epidemic status and potential immune escape mechanisms of Omicron variants. Especially, we focused on the potential roles of viral epitope mutations, antigenic drift, hybrid immunity, and "original antigenic sin" in mediating immune evasion. These insights might supply more valuable concise information for us to understand the spreading of Omicron variants.

The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19), is spreading worldwide. Although the COVID-19 epidemic has passed its peak of transmission, the harm it has caused deserves our attention. Scientists are striving to develop medications that can effectively treat COVID-19 symptoms without causing any adverse reactions. SARS-CoV-2 inhibitory peptides derived from animal proteins have a wide range of functional activities in addition to safety. Identifying animal protein sources is crucial to obtaining SARS-CoV-2 inhibitory peptides from animal sources. This review aims to reveal the mechanisms of action of these peptides on SARS-CoV-2 and the possibility of animal proteins as a material source of SARS-CoV-2 inhibitory peptides. Also, it introduces the utilization of computer-aided design methods, phage display, and drug delivery strategies in the research on SARS-CoV-2 inhibitor peptides from animal proteins. In order to identify new antiviral peptides and boost their efficiency, we recommend investigating the interaction between SARS-CoV-2 inhibitory peptides from animal protein sources and non-structural proteins (Nsps) using a variety of technologies, including computer-aided drug approaches, phage display techniques, and drug delivery techniques. This article provides useful information for the development of novel anti-COVID-19 drugs.

Over the last 24 months, there has been growing evidence of a correlation between mRNA COVID-19 vaccine boosters and increased prevalence of COVID-19 infection and other pathologies. Recent works have added possible causation to correlation. mRNA vaccine boosters may impair immune system response in immune compromised individuals. Multiple doses of the mRNA COVID-19 vaccines may result in much higher levels of IgG 4 antibodies, or also impaired activation of CD4 + and CD8 + T cells. The opportunity for mRNA vaccine boosters to impair the immune system response needs careful consideration, as this impacts the cost-to-benefit ratio of the boosters' practice.

SARS-CoV-2 continues to impact human health globally, with airborne transmission being a significant mode of transmission. In addition to tools like vaccination and testing, countermeasures that reduce viral spread in indoor settings are critical. This study aims to assess the efficacy of UV-C light, utilizing the Violett sterilization device, as a countermeasure against airborne transmission of SARS-CoV-2 in the highly susceptible Golden Syrian hamster model.

Two cohorts of naïve hamsters were subjected to airborne transmission from experimentally infected hamsters; one cohort was exposed to air treated with UV-C sterilization, while the other cohort was exposed to untreated air.

Treatment of air with UV-C light prevented the airborne transmission of SARS-CoV-2 from the experimentally exposed hamster to naïve hamsters. Notably, this protection was sustained over a multi-day exposure period during peak viral shedding by hamsters.

These findings demonstrate the efficacy of the UV-C light to mitigate against airborne SARS-CoV-2 transmission. As variants continue to emerge, UV-C light holds promise as a tool for reducing infections in diverse indoor settings, ranging from healthcare facilities to households. This study reinforces the urgency of implementing innovative methods to reduce airborne disease transmission and safeguard public health against emerging biological threats.

Wastewater-based genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provides a comprehensive approach to characterize evolutionary patterns and distribution of viral types in a population. This study documents the molecular epidemiology of SARS-CoV-2, in Northern South Africa, from January 2021 to May 2022.

A total of 487 wastewater samples were collected from the influent of eight wastewater treatment facilities and tested for SARS-CoV-2 RNA using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). SARS-CoV-2 positive samples with genome copies/mL ≥1,500 were subjected to allele-specific genotyping (ASG) targeting the Spike protein; 75 SARS-CoV-2 positive samples were subjected to whole genome sequencing (WGS) on the ATOPlex platform. Variants of concern (VoC) and lineages were assigned using the Nextclade and PangoLIN Software. Concordance for VoC between ASG and WGS analyses was determined. Sequence relationship was determined by phylogenetic analysis.

Seventy-five percent (365/487) of the influent samples were positive for SARS-CoV-2 RNA. Delta and Omicron VoC were more predominant at a prevalence of 45 and 32%, respectively, and they were detected as early as January and February 2021, while Beta VoC was least detected at a prevalence of 5%. A total of 11/60 (18%) sequences were assigned lineages and clades only, but not a specific VoC name. Phylogenetic analysis was used to investigate the relationship of these sequences to other study sequences, and further characterize them. Concordance in variant assignment between ASG and WGS was seen in 51.2% of the study sequences. There was more intra-variant diversity among Beta VoC sequences; mutation E484K was absent. Three previously undescribed mutations (A361S, V327I, D427Y) were seen in Delta VoC.

The detection of Delta and Omicron VoCs in study sites earlier in the outbreak than has been reported in other regions of South Africa highlights the importance of population-based approaches over individual sample-based approaches in genomic surveillance. Inclusion of non-Spike protein targets could improve the specificity of ASG, since all VoCs share similar Spike protein mutations. Finally, continuous molecular epidemiology with the application of sensitive technologies such as next generation sequencing (NGS) is necessary for the documentation of mutations whose implications when further investigated could enhance diagnostics, and vaccine development efforts.

Risk management and control of airborne transmission in hospitals is crucial in response to a respiratory virus pandemic. However, the formulation of these infection control measures is often based on epidemiological investigations, which are an indirect way of analyzing the transmission route of viruses. This can lead to careless omissions in infection prevention and control or excessively restrictive measures that increase the burden on healthcare workers. The study provides a starting point for standardizing transmission risk management in designated hospitals by systemically monitoring viruses in the air of typical spaces in COVID-19 hospitals. The negative results of 359 air samples in the clean and emergency zones demonstrated the existing measures to interrupt airborne transmission in a designated COVID-19 hospital. Some positive cases in the corridor of the contaminant zone during rounds and meal delivery highlighted the importance of monitoring airborne viruses for interrupting nosocomial infection.

The emergence of Omicron as the fifth variant of concern within the SARS-CoV-2 pandemic in late 2021, characterized by its rapid transmission and distinct spike gene mutations, underscored the pressing need for cost-effective and efficient methods to detect viral variants, especially given their evolving nature. This study sought to address this need by assessing the effectiveness of two SARS-CoV-2 variant classification platforms based on RT-PCR and mass spectrometry. The primary aim was to differentiate between Delta, Omicron BA.1, and Omicron BA.2 variants using 618 COVID-19-positive samples collected from Bangkok patients between November 2011 and March 2022. The analysis revealed that both BA.1 and BA.2 variants exhibited significantly higher transmission rates, up to 2-3 times, when compared to the Delta variant. This research presents a cost-efficient approach to virus surveillance, enabling a quantitative evaluation of variant-specific public health implications, crucial for informing and adapting public health strategies.

Portable assays for the rapid identification of lineages of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to aid large-scale efforts in monitoring the evolution of the virus. Here we report a multiplexed assay in a microarray format for the detection, via isothermal amplification and plasmonic-gold-enhanced near-infrared fluorescence, of variants of SARS-CoV-2. The assay, which has single-nucleotide specificity for variant discrimination, single-RNA-copy sensitivity and does not require RNA extraction, discriminated 12 lineages of SARS-CoV-2 (in three mutational hotspots of the Spike protein) and detected the virus in nasopharyngeal swabs from 1,034 individuals at 98.8% sensitivity and 100% specificity, with 97.6% concordance with genome sequencing in variant discrimination. We also report a compact, portable and fully automated device integrating the entire swab-to-result workflow and amenable to the point-of-care detection of SARS-CoV-2 variants. Portable, rapid, accurate and multiplexed assays for the detection of SARS-CoV-2 variants and lineages may facilitate variant-surveillance efforts.