The highly conserved stem-loop II motif is dispensable for SARS-CoV-2 (preprint)

The stem-loop II motif (s2m) is a RNA structural element that is found in the 3' untranslated region (UTR) of many RNA viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Though the motif was discovered over twenty-five years ago, its functional significance is unknown. In order to understand the importance of s2m, we created viruses with deletions or mutations of the s2m by reverse genetics and also evaluated a clinical isolate harboring a unique s2m deletion. Deletion or mutation of the s2m had no effect on growth in vitro, or growth and viral fitness in Syrian hamsters in vivo. We also compared the secondary structure of the 3' UTR of wild type and s2m deletion viruses using SHAPE-MaP and DMS-MaPseq. These experiments demonstrate that the s2m forms an independent structure and that its deletion does not alter the overall remaining 3'UTR RNA structure. Together, these findings suggest that s2m is dispensable for SARS-CoV-2.

Modeling COVID-19 vaccination strategies in LMICs considering uncertainty in viral evolution and immunity (preprint)

Vaccines against the SARS-CoV-2 virus were developed in record time, but their distribution has been highly unequal. With demand saturating in high-income countries, many low- and middle-income countries (LMIC) finally have an opportunity to acquire COVID-19 vaccines. But the pandemic has taken its toll, and a majority of LMIC populations have partial immunity to COVID-19 disease due primarily to viral infection. This existing immunity, combined with resource limitations, raises the question of how LMICs should prioritize COVID-19 vaccines relative to other competing health priorities. We modify an established computational model, Covasim, to address these questions in four diverse country-like settings under a variety of viral evolution, vaccine delivery, and novel immunity scenarios. Under continued Omicron-like viral evolution and mid-level immunity assumptions, results show that COVID-19 vaccines could avert up to 2 deaths per 1,000 doses if administered to high-risk (60+) populations as prime+boost or annual boosting campaigns. Similar immunization efforts reaching healthy children and adults would avert less than 0.1 deaths per 1,000 doses. Together, these modeling results can help to support normative guidelines and programmatic decision making towards objectively maximizing population health.

The real-world effectiveness of an intranasal spray A8G6 antibody cocktail in the post-exposure prophylaxis of COVID-19 (preprint)

BackgroundDue to the continuous appearance of novel SARS-CoV-2 variants that are resistant to approved antibodies and leading to the epidemic rebound, several approved neutralizing antibodies have been paused for their usage against COVID-19. Previously, we identified A8G6, an antibody combination of two synergic SARS-CoV-2 neutralizing antibodies 55A8 and 58G6, that showed broad neutralizing activities against Omicron variants. When administrated by the nasal spray delivery system, A8G6 showed promising efficacy in COVID-19 animal models and also showed favorable safety profile in preclinical models as well as in a first-in-human trial. The aim of this study is to evaluate the real-world efficacy of A8G6 neutralizing antibody nasal spray in post-exposure prevention of COVID-19. MethodsFrom November 27, 2022 to January 31, 2023, an open-label, non-randomized, two-arm, blank-controlled, investigator-initiated trial was conducted in Chongqing, China. High-risk healthy participants (18-65 years) within 72 hours after close contact to SARS-CoV-2 infected individuals were recruited and received a three-dose (1.4 mg/dose) A8G6 nasal spray treatment daily or no treatment (blank control) for 7 consecutive days. The primary end points were 1) the occurrence of positive SARS-CoV-2 RT-PCR cases in A8G6 treated group vs blank control group at the end of day 7; 2) time to SARS-CoV-2 positive conversion at the end of day 7. The secondary end points were 1) viral load of SARS-CoV-2 when participants became SARS-CoV-2 positive; 2) the time from SARS-CoV-2 infection to negative COVID-19 conversion. Safety end point of the nasal spray AG86 was analyzed by recording adverse events during the whole course of this trial. This study was registered with Chictr.org (ChiCTR2200066416). FindingsOf 513 enrolled participants, 173 in the A8G6 treatment group and 340 in the blank-control group were included in the analysis. SARS-CoV-2 infection occurred in 151/340 (44.4%) subjects in the blank control group and 12/173 (6.9%) subjects with the A8G6 treatment group. The result indicates that the intranasal spray A8G6 reduces the risk of SARS-CoV-2 infection (HR=0.12, 95% CI, 0.07-0.22; p<0.001). The prevention efficacy of the A8G6 treatment within 72-hours exposure was calculated to be 84.4% (95% CI: 74.4%-90.4%). Moreover, compared to the blank-control group, the time from the SARS-CoV-2 negative to the positive COVID-19 conversion was significantly longer in the AG86 treatment group (mean time: 3.4 days in the A8G6 treatment group vs 2.6 days in the control group, p=0.019). In the secondary end-point analysis, the A8G6 nasal treatment had no effects on the viral load at baseline SARS-CoV-2 RT-PCR positivity and the time of the negative COVID-19 conversion (viral clearance). Finally, 5 participants (3.1%) in the treatment group reported general adverse effects. We did not observe any severe adverse effects related to the A8G6 treatment in this study. InterpretationIn this study, the intranasal spray AG86 antibody cocktail showed potent efficacy for prevention of SARS-CoV-2 infection in close contacts of COVID-19 patients. FundingChongqing Biomedical R&D Major Special Project, Project (No. CSTB2022TIAD-STX0013), Chongqing Science and Health Joint Medical High-end Talent Project (No. 2022GDRC012), Science and Technology Research Program of Chongqing Municipal Education Commission (No. KJZD-K202100402), CQMU Program for Youth Innovation in Future Medicine (No. W0073). Research in contextO_ST_ABSEvidence before the studyC_ST_ABSTwo potent neutralizing antibodies 55A8 and 58G6 against SARS-CoV-2 were identified from the plasma of COVID-19 convalescent patients. In our previous studies, the synergetic neutralization of the antibody combination of 55A8 and 58G6 (A8G6) had been shown in structural mechanism, as well as in vitro and in vivo. Pre-clinical evaluation of A8G6 nasal spray showed promising efficacy against Omicron BA.4/5 infection in golden syrian hamsters challenged with live virus. In a first-in-human trial, A8G6 also showed favorable safety profile and nasal concentration over IC90 of neutralization activity against Omicron BA.4/5. The preliminary data showed that the intranasal spray A8G6 had the excellent efficacy, safety and druggability to protect against COVID-19. Added value of this studyThis is the first human trial showing that a nasal spray of neutralizing antibody cocktail is efficacious in preventing SARS-CoV-2 infection but is not efficacious in the post-infection treatment of COVID-19. In the Omicron wave of the COVID-19 pandemic in China in November, 2022, COVID-19 close contacts receiving the A8G6 treatment in the designated quarantine hotels showed a significantly lower incidence of SARS-CoV-2 infection. Additionally, the A8G6 treatment delayed time from exposure to the diagnosis of the COVID-19 positivity (median time: 3.4 days in the treatment group vs 2.6 days in the control group). Furthermore, we analyzed the effects of the A8G6 treatment on the clinical status of close contacts who became infected with SARS-CoV-2. Results suggests that there were no significant differences in viral load of SARS-CoV-2 at the beginning of positive infection and the time of the viral clearance between A8G6 treatment and blank control groups. Overall, the trial result is consistent with the mechanism of action of nasal spray antibody cocktail for the prevention of SARS-CoV-2 infection. Finally, low safety risk of the nasal spray A8G6 was also shown in the trial. Implications of all the available evidenceWe observed the use of A8G6 to reduce the risk of SARS-CoV-2 infection. This study provided supporting evidences for the real-world effectiveness and safety of the nasal spray A8G6 among high-risk close contacts in the post-exposure prevention of COVID-19 during the Omicron BA.5.2 wave in China. This is the first proof of concept of using nasal spray neutralizing antibody for the prevention of viral infection. It implicates that the promising efficacy of the nasal spray A8G6 makes it possible for the fast-acting prevention in future COVID-19 waves.

Coordinated nasal mucosa-mediated immunity accelerates recovery from COVID-19 (preprint)

Viral infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induce a dynamic immune environment. Using nasal mucosal samples in 139 participants from the STOIC study (community-based randomised clinical trial for the use of budesonide in early onset SARS-CoV-2, NCT04416399), we applied predefined immune mediator nodes in relation to clinical outcomes and viral burden. Interferon- and chemokine-dominant nodes increased expression as compared to health, validating our modular approach. Next, we demonstrated that an increase in mucosal immunity-like node consisting of CCL13, CCL17, IL-33, among others was associated with a mean 3.7-day quicker recovery with no primary outcome events, irrespective of treatment arm. By day 14 the mucosal node divided into two daughter nodes linked to interferon molecules and was transcriptionally detectable in nasal cavity basal, hillock and ciliated cells (as per public single cell dataset EGAD00001007718). Our data suggest mucosal-associated mediators are key for early symptom resolution of SARS-CoV-2.

Association of SARS-CoV-2 Nucleocapsid Protein Mutations with Patient Demographic and Clinical Characteristics during the Delta and Omicron Waves (preprint)

SARS-CoV-2 genomic mutations outside the spike protein that may increase transmissibility and disease severity have not been well characterized. This study identified mutations in the nucleocapsid protein and their possible association with patient characteristics. We analyzed 695 samples from patients with confirmed COVID-19 in Saudi Arabia between April 1, 2021, and April 30, 2022. Nucleocapsid protein mutations were identified through whole genome sequencing. {chi}2 tests and T tests assessed associations between mutations and patient characteristics. Logistic regression estimated risk of intensive care unit (ICU) admission or death. Of 60 mutations identified, R203K was most common followed by G204R, P13L, and E31del, R32del, and S33del. These mutations were associated with reduced risk of ICU admission. P13L, E31del, R32del, and S33del were also associated with reduced risk of death. By contrast, D63G, R203M, and D377Y were associated with increased risk of ICU admission. Most mutations were detected in the SR-rich region, which was associated with low risk of death. C-tail and central linker regions were associated with increased risk of ICU admission, whereas the N-arm region was associated with reduced ICU admission risk. Some SARS-CoV-2 nucleocapsid amino acid mutations may enhance viral infection and COVID-19 disease severity.

Type I interferon signaling induces a delayed antiproliferative response in Calu-3 cells during SARS-CoV-2 infection (preprint)

Disease progression during SARS-CoV-2 infection is tightly linked to the fate of lung epithelial cells, with severe cases of COVID-19 characterized by direct injury of the alveolar epithelium and an impairment in its regeneration from progenitor cells. The molecular pathways that govern respiratory epithelial cell death and proliferation during SARS-CoV-2 infection, however, remain poorly understood. We now report a high-throughput CRISPR screen for host genetic modifiers of the fitness of SARS-CoV-2-infected Calu-3 respiratory epithelial cells. The top 4 genes identified in our screen encode components of the same type I interferon signaling complex - IFNAR1, IFNAR2, JAK1, and TYK2. The 5th gene, ACE2, was an expected control encoding the SARS-CoV-2 viral receptor. Surprisingly, despite the antiviral properties of IFN-I signaling, its disruption in our screen was associated with an increase in Calu-3 cell fitness. We validated this effect and found that IFN-I signaling did not sensitize SARS-CoV-2-infected cultures to cell death but rather inhibited the proliferation of surviving cells after the early peak of viral replication and cytopathic effect. We also found that IFN-I signaling alone, in the absence of viral infection, was sufficient to induce this delayed antiproliferative response. Together, these findings highlight a cell autonomous antiproliferative response by respiratory epithelial cells to persistent IFN-I signaling during SARS-CoV-2 infection. This response may contribute to the deficient alveolar regeneration that has been associated with COVID-19 lung injury and represents a promising area for host-targeted therapeutic development.

Using Discarded Facial Tissues to Monitor and Diagnose Viral Respiratory Infections.

Molecular biology amplification enables sensitive detection of most respiratory viruses through nasopharyngeal swabbing. We developed an innovative approach to detect viral genomes on used facial tissues. In 2 communities of children, used tissues were collected once weekly for 1 year. Pooled analysis of tissues enabled detection of successive virus circulation in 4 age groups over time and forecasted by several weeks the circulation of influenza in the general population. At the individual level, in a proof-of-concept study of 30 volunteers with influenza-like signs/symptoms, we identified common respiratory viruses. The signals for SARS-CoV-2 obtained in parallel from 15 facial tissues and swab samples were similar and often higher for the tissues (11/15). Individual analysis of tissues offers a noninvasive, sensitive, and affordable alternative to self-sampling without a medical care requirement. Pooled analyses may be used to detect virus spread in specific communities, predict seasonal epidemics, and alert the population to viral infections.

Regulatory dissection of the severe COVID-19 risk locus introgressed by Neanderthals.

Individuals infected with the SARS-CoV-2 virus present with a wide variety of symptoms ranging from asymptomatic to severe and even lethal outcomes. Past research has revealed a genetic haplotype on chromosome 3 that entered the human population via introgression from Neanderthals as the strongest genetic risk factor for the severe response to COVID-19. However, the specific variants along this introgressed haplotype that contribute to this risk and the biological mechanisms that are involved remain unclear. Here, we assess the variants present on the risk haplotype for their likelihood of driving the genetic predisposition to severe COVID-19 outcomes. We do this by first exploring their impact on the regulation of genes involved in COVID-19 infection using a variety of population genetics and functional genomics tools. We then perform a locus-specific massively parallel reporter assay to individually assess the regulatory potential of each allele on the haplotype in a multipotent immune-related cell line. We ultimately reduce the set of over 600 linked genetic variants to identify four introgressed alleles that are strong functional candidates for driving the association between this locus and severe COVID-19. Using reporter assays in the presence/absence of SARS-CoV-2, we find evidence that these variants respond to viral infection. These variants likely drive the locus' impact on severity by modulating the regulation of two critical chemokine receptor genes: CCR1 and CCR5. These alleles are ideal targets for future functional investigations into the interaction between host genomics and COVID-19 outcomes.

Non-Pharmacological Therapies for Post-Viral Syndromes, Including Long COVID: A Systematic Review.

BACKGROUND: Post-viral syndromes (PVS), including Long COVID, are symptoms sustained from weeks to years following an acute viral infection. Non-pharmacological treatments for these symptoms are poorly understood. This review summarises the evidence for the effectiveness of non-pharmacological treatments for PVS. METHODS: We conducted a systematic review to evaluate the effectiveness of non-pharmacological interventions for PVS, as compared to either standard care, alternative non-pharmacological therapy, or placebo. The outcomes of interest were changes in symptoms, exercise capacity, quality of life (including mental health and wellbeing), and work capability. We searched five databases (Embase, MEDLINE, PsycINFO, CINAHL, MedRxiv) for randomised controlled trials (RCTs) published between 1 January 2001 to 29 October 2021. The relevant outcome data were extracted, the study quality was appraised using the Cochrane risk-of-bias tool, and the findings were synthesised narratively. FINDINGS: Overall, five studies of five different interventions (Pilates, music therapy, telerehabilitation, resistance exercise, neuromodulation) met the inclusion criteria. Aside from music-based intervention, all other selected interventions demonstrated some support in the management of PVS in some patients. INTERPRETATION: In this study, we observed a lack of robust evidence evaluating the non-pharmacological treatments for PVS, including Long COVID. Considering the prevalence of prolonged symptoms following acute viral infections, there is an urgent need for clinical trials evaluating the effectiveness and cost-effectiveness of non-pharmacological treatments for patients with PVS. REGISTRATION: The study protocol was registered with PROSPERO [CRD42021282074] in October 2021 and published in BMJ Open in 2022.

Quinones as Promising Compounds against Respiratory Viruses: A Review.

Respiratory viruses represent a world public health problem, giving rise to annual seasonal epidemics and several pandemics caused by some of these viruses, including the COVID-19 pandemic caused by the novel SARS-CoV-2, which continues to date. Some antiviral drugs have been licensed for the treatment of influenza, but they cause side effects and lead to resistant viral strains. Likewise, aerosolized ribavirin is the only drug approved for the therapy of infections by the respiratory syncytial virus, but it possesses various limitations. On the other hand, no specific drugs are licensed to treat other viral respiratory diseases. In this sense, natural products and their derivatives have appeared as promising alternatives in searching for new compounds with antiviral activity. Besides their chemical properties, quinones have demonstrated interesting biological activities, including activity against respiratory viruses. This review summarizes the activity against respiratory viruses and their molecular targets by the different types of quinones (both natural and synthetic). Thus, the present work offers a general overview of the importance of quinones as an option for the future pharmacological treatment of viral respiratory infections, subject to additional studies that support their effectiveness and safety.

Vitamin D3 Supplementation at 5000 IU Daily for the Prevention of Influenza-like Illness in Healthcare Workers: A Pragmatic Randomized Clinical Trial.

Vitamin D supplementation has been shown to reduce the incidence of acute respiratory infections in populations at risk. The COVID-19 pandemic has highlighted the importance of preventing viral infections in healthcare workers. The aim of this study was to assess the hypothesis that vitamin D3 supplementation at 5000 IU daily reduces influenza-like illness (ILI), including COVID-19, in healthcare workers. We conducted a prospective, controlled trial at a tertiary university hospital. A random group of healthcare workers was invited to receive 5000 IU daily vitamin D3 supplementation for nine months, while other random healthcare system workers served as controls. All healthcare workers were required to self-monitor and report to employee health for COVID-19 testing when experiencing symptoms of ILI. COVID-19 test results were retrieved. Incidence rates were compared between the vitamin D and control groups. Workers in the intervention group were included in the analysis if they completed at least 2 months of supplementation to ensure adequate vitamin D levels. The primary analysis compared the incidence rate of all ILI, while secondary analyses examined incidence rates of COVID-19 ILI and non-COVID-19 ILI. Between October 2020 and November 2021, 255 healthcare workers (age 47 ± 12 years, 199 women) completed at least two months of vitamin D3 supplementation. The control group consisted of 2827 workers. Vitamin D3 5000 IU supplementation was associated with a lower risk of ILI (incidence rate difference: -1.7 × 10-4/person-day, 95%-CI: -3.0 × 10-4 to -3.3 × 10-5/person-day, p = 0.015) and a lower incidence rate for non-COVID-19 ILI (incidence rate difference: -1.3 × 10-4/person-day, 95%-CI -2.5 × 10-4 to -7.1 × 10-6/person-day, p = 0.038). COVID-19 ILI incidence was not statistically different (incidence rate difference: -4.2 × 10-5/person-day, 95%-CI: -10.0 × 10-5 to 1.5 × 10-5/person-day, p = 0.152). Daily supplementation with 5000 IU vitamin D3 reduces influenza-like illness in healthcare workers.

mRNA vaccines: The future of prevention of viral infections?

Messenger RNA (mRNA) vaccines against COVID-19 are the first authorized biological preparations developed using this platform. During the pandemic, their administration has been proven to be a life-saving intervention. Here, we review the main advantages of using mRNA vaccines, identify further technological challenges to be met during the development of the mRNA platform, and provide an update on the clinical progress on leading mRNA vaccine candidates against different viruses that include influenza viruses, human immunodeficiency virus 1, respiratory syncytial virus, Nipah virus, Zika virus, human cytomegalovirus, and Epstein-Barr virus. The prospects and challenges of manufacturing mRNA vaccines in low-income countries are also discussed. The ongoing interest and research in mRNA technology are likely to overcome some existing challenges for this technology (e.g., related to storage conditions and immunogenicity of some components of lipid nanoparticles) and enhance the portfolio of vaccines against diseases for which classical formulations are already authorized. It may also open novel pathways of protection against infections and their consequences for which no safe and efficient immunization methods are currently available.

Comprehensive Investigations Relationship Between Viral Infections and Multiple Sclerosis Pathogenesis.

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS). Compared to other types of self-limiting myelin disorders, MS compartmentalizes and maintains chronic inflammation in the CNS. Even though the exact cause of MS is unclear, it is assumed that genetic and environmental factors play an important role in susceptibility to this disease. The progression of MS is triggered by certain environmental factors, such as viral infections. The most important viruses that affect MS are Epstein-Barr virus (EBV), human herpes virus 6 (HHV-6), human endogenous retrovirus (HERV), cytomegalovirus (CMV), and varicella zoster virus (VZV). These viruses all have latent stages that allow them to escape immune detection and reactivate after exposure to various stimuli. Furthermore, their tropism for CNS and immune system cells explains their possible deleterious function in neuroinflammation. In this study, the effect of viral infections on MS disease focuses on the details of viruses that can change the risk of the disease. Paying attention to the most recent articles on the role of SARS-CoV-2 in MS disease, laboratory indicators show the interaction of the immune system with the virus. Also, strategies to prevent viruses that play a role in triggering MS are discussed, such as EBV, which is one of the most important.

Revisiting Regulated Cell Death Responses in Viral Infections.

The fate of a viral infection in the host begins with various types of cellular responses, such as abortive, productive, latent, and destructive infections. Apoptosis, necroptosis, and pyroptosis are the three major types of regulated cell death mechanisms that play critical roles in viral infection response. Cell shrinkage, nuclear condensation, bleb formation, and retained membrane integrity are all signs of osmotic imbalance-driven cytoplasmic swelling and early membrane damage in necroptosis and pyroptosis. Caspase-driven apoptotic cell demise is considered in many circumstances as an anti-inflammatory, and some pathogens hijack the cell death signaling routes to initiate a targeted attack against the host. In this review, the selected mechanisms by which viruses interfere with cell death were discussed in-depth and were illustrated by compiling the general principles and cellular signaling mechanisms of virus-host-specific molecule interactions.

Asthma exacerbations: the Achilles heel of asthma care.

Asthma exacerbations significantly impact millions of patients worldwide to pose large disease burdens on affected patients, families, and health-care systems. Although numerous environmental factors cause asthma exacerbations, viral respiratory infections are the principal triggers. Advances in the pathophysiology of asthma have elucidated dysregulated protective immune responses and upregulated inflammation that create susceptibility and risks for exacerbation. Biologics for the treatment of severe asthma reduce rates of exacerbations and identify specific pathways of inflammation that contribute to altered pathophysiology, novel therapeutic targets, and informative biomarkers. Major steps to prevent exacerbations include the identification of molecular pathways whose blockage will prevent asthma attacks safely, predictably, and effectively.

Causal Associations Between Ulcerative Colitis and COVID-19: A Bidirectional Mendelian Randomization Study (preprint)

Background Corona Virus Disease 2019(COVID-19) has put human health and medical resources under strain since 2019. However, it’s still equivocal whether ulcerative colitis (UC) and COVID-19 have a bidirectional causal relationship, so we attempted to clarify this issue using two-sample mendelian randomization (two-sample MR) analysis.Methods To explore the relationship between ulcerative colitis and COVID-19, we obtained summary statistics from the GWAS database and used single nucleotide polymorphisms (SNPs) as a genetic tool. The inverse-variance weighted (IVW) method was chosen as the primary analytical method for two-sample Mendelian randomization analysis, complemented by a combination of MR-egger. Further validation using sensitivity analysis such as Q-test, MR-PRESSO, MR-Egger intercepts method.Result All forward MR analyses demonstrated that UC has a significant susceptibility and severity to COVID-19, 1. COVID-19 vs population: IVW (OR = 1.053; CI, 1.012–1.096; P = 0.009) and MR Egger (OR = 1.015; CI, 0.946–1.089; P = 0.672). 2.hospitalized vs population: IVW (OR = 1.080; CI, 1.004–1.162; P = 0.037) and MR Egger (OR = 1.009; CI, 0.882–1.153; P = 0.898). 3. very severe respiratory confirmed vs population: IVW (OR = 1.187; CI, 1.018–1.384; P = 0.027) and MR Egger (OR = 1.104; CI, 0.801–1.521; P = 0.554). In the bidirectional MR study, the P values (P > 0.05) obtained by several methods were not statistically significant.Conclusion There is significant evidence that UC is both a risk factor for COVID-19 and may increase the risk of COVID-19. However, there is no reverse causal relationship between the two diseases.

MVIP: multi-omics portal of viral infection.

Virus infections are huge threats to living organisms and cause many diseases, such as COVID-19 caused by SARS-CoV-2, which has led to millions of deaths. To develop effective strategies to control viral infection, we need to understand its molecular events in host cells. Virus related functional genomic datasets are growing rapidly, however, an integrative platform for systematically investigating host responses to viruses is missing. Here, we developed a user-friendly multi-omics portal of viral infection named as MVIP (https://mvip.whu.edu.cn/). We manually collected available high-throughput sequencing data under viral infection, and unified their detailed metadata including virus, host species, infection time, assay, and target, etc. We processed multi-layered omics data of more than 4900 viral infected samples from 77 viruses and 33 host species with standard pipelines, including RNA-seq, ChIP-seq, and CLIP-seq, etc. In addition, we integrated these genome-wide signals into customized genome browsers, and developed multiple dynamic charts to exhibit the information, such as time-course dynamic and differential gene expression profiles, alternative splicing changes and enriched GO/KEGG terms. Furthermore, we implemented several tools for efficiently mining the virus-host interactions by virus, host and genes. MVIP would help users to retrieve large-scale functional information and promote the understanding of virus-host interactions.

VThunter: a database for single-cell screening of virus target cells in the animal kingdom.

Viral infectious diseases are a devastating and continuing threat to human and animal health. Receptor binding is the key step for viral entry into host cells. Therefore, recognizing viral receptors is fundamental for understanding the potential tissue tropism or host range of these pathogens. The rapid advancement of single-cell RNA sequencing (scRNA-seq) technology has paved the way for studying the expression of viral receptors in different tissues of animal species at single-cell resolution, resulting in huge scRNA-seq datasets. However, effectively integrating or sharing these datasets among the research community is challenging, especially for laboratory scientists. In this study, we manually curated up-to-date datasets generated in animal scRNA-seq studies, analyzed them using a unified processing pipeline, and comprehensively annotated 107 viral receptors in 142 viruses and obtained accurate expression signatures in 2 100 962 cells from 47 animal species. Thus, the VThunter database provides a user-friendly interface for the research community to explore the expression signatures of viral receptors. VThunter offers an informative and convenient resource for scientists to better understand the interactions between viral receptors and animal viruses and to assess viral pathogenesis and transmission in species. Database URL: https://db.cngb.org/VThunter/.