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1.
Journal of Social Work in End-of-Life & Palliative Care ; : 1-16, 2022.
Article in English | Taylor & Francis | ID: covidwho-1819738
2.
Cell Discovery ; 8(1):38-38, 2022.
Article in English | PMC | ID: covidwho-1815520

ABSTRACT

The global COVID-19 epidemic has spread rapidly around the world and caused the death of more than 5 million people. It is urgent to develop effective strategies to treat COVID-19 patients. Here, we revealed that SARS-CoV-2 infection resulted in the dysregulation of genes associated with NAD + metabolism, immune response, and cell death in mice, similar to that in COVID-19 patients. We therefore investigated the effect of treatment with NAD + and its intermediate (NMN) and found that the pneumonia phenotypes, including excessive inflammatory cell infiltration, hemolysis, and embolization in SARS-CoV-2-infected lungs were significantly rescued. Cell death was suppressed substantially by NAD + and NMN supplementation. More strikingly, NMN supplementation can protect 30% of aged mice infected with the lethal mouse-adapted SARS-CoV-2 from death. Mechanically, we found that NAD + or NMN supplementation partially rescued the disturbed gene expression and metabolism caused by SARS-CoV-2 infection. Thus, our in vivo mouse study supports trials for treating COVID-19 patients by targeting the NAD + pathway.

3.
Research on Social Work Practice ; : 1, 2022.
Article in English | Academic Search Complete | ID: covidwho-1808085

ABSTRACT

Objective: This study aimed to test the feasibility and efficacy of a self-guided online cognitive behaviour therapy (iCBT) for university students in Hong Kong during COVID-19. Method: One group pre-post-test design with convenient sampling was adopted in this study, involving 84 university students who received a newly developed iCBT within an 8 week intervention period. The iCBT offered eight online modules for students to learn the skills of CBT at home through an online platform which was accessible any time anywhere anonymously with technical support only. Standardized assessment tools were used for outcomes assessment at the pre- and post-intervention periods. Results: Three quarters of participants completed all iCBT modules. The results of paired t-tests showed that, after completing the iCBT, participants showed reduction in anxiety, depression, and perceived stress. Conclusion: This study provides preliminary evidences to support the feasibility and efficacy of the self-guided iCBT for university students during COVID-19. [ FROM AUTHOR] Copyright of Research on Social Work Practice is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

4.
PloS one ; 17(4), 2022.
Article in English | EuropePMC | ID: covidwho-1800807

ABSTRACT

Objective We aimed to explore factors affecting family health management during home quarantine as well as the effects of variations in family health management (FHM) on individuals’ health status. Methods Using stratified random sampling, 618 families in Wuhan as well as cities within its surrounding provinces were recruited and surveyed online. Latent class variables were extracted from four modules: disinfection, space layout, physical exercise, and food reserves. The analysis was conducted using the poLCA package in R software (v.4.1.0). Chi-squared tests, Fisher’s exact tests, and non-parametric Kruskal–Wallis tests were used to compare groups as appropriate. Results We found an overall questionnaire reliability of 0.77 and a total omega of 0.92, indicating that the survey results were credible. The Bayesian information criterion and Akaike information criterion were used to identified four latent class variables, namely latent non-family health management (18.9%) and latent low, medium, and advanced FHM (30.93%, 29.49%, and 20.59%, respectively). Gender, household income level, body mass index, the presence of a nearby community hospital, and self-rated health status showed statistically significant differences with respect to latent FHM. Moreover, we found a statistically significant difference in emotional reactions when comparing latent advanced and low to mid-level latent FHM. Compared with latent non-family health managers, we detected statistically significant differences in individual energy levels between potential family health managers at latent low and medium levels. Additionally, we found statistically significant differences in individual energy levels between latent advanced and low level family health managers. Conclusions We found that multiple factors, including gender, household income, and body mass index, were correlated with latent FHM during home quarantine. We conclude that FHM can meaningfully improve individuals’ health. Thus, increasing social support for individuals can improve FHM as well as individuals’ health during home quarantine.

5.
Front Microbiol ; 13: 828806, 2022.
Article in English | MEDLINE | ID: covidwho-1793005

ABSTRACT

The coronavirus disease 2019 (COVID-19) vaccines have very successfully decreased the disease risk as we know; some key information remains unknown due to the short development history and the lack of long-term follow-up studies in vaccinated populations. One of the unanswered issues is the protection duration conferred after COVID-19 vaccination, which appears to play a pivotal role in the future impact of pathogens and is critical to inform the public health response and policy decisions. Here, we review current information on the long-term effectiveness of different COVID-19 vaccines, persistence of immunogenicity, and gaps in knowledge. Meanwhile, we also discuss the influencing factors and future study prospects on this topic.

6.
BMC Psychol ; 10(1): 87, 2022 Apr 04.
Article in English | MEDLINE | ID: covidwho-1775351

ABSTRACT

BACKGROUND: The sudden outbreak of COVID-19 had a great impact on the physical and mental health of people all over the world, especially for students whose physical and mental development was not yet mature. In order to understand the physical and mental conditions of students during the epidemic period and provide a theoretical basis for coping with psychological problems in public health emergencies, this study explored the mediating role of sleep disorders in the effect of the psychological stress response (PSR) on non-suicidal self-injury (NSSI), along with the moderating role of emotional management ability (EMA). METHODS: The SRQ-20, Pittsburgh Sleep Quality Index, NSSI Behavior Questionnaire, and Emotional Management Questionnaire were used to investigate the mental health of Chinese students in April 10-20 (Time point 1, T1) and May 20-30 (Time point 2, T2), 2020. A total of 1,955 students (Mage = 19.64 years, 51.4% male) were examined at T1 and 342 students (Mage = 20.06 years, 48.2% male) were reassessed at T2. RESULTS: Overall, the detection rate of PSR and NSSI were 17.60% (n = 344) and 24.90% (n = 486) respectively in the T1 sample, and were 16.37% (n = 56) and 25.44% (n = 87), in the T2 sample. We also found that sleep disorders played a mediating role in the effect of PSR on NSSI in the T1 and T2 samples. In addition, EMA was shown to regulate the effect of PSR on sleep disorders and the effect of sleep disorders on NSSI in the T1 samples. CONCLUSION: We found that PSR resulting from public health emergency might lead to NSSI behaviors in individuals. PSR may also cause sleep disorders, which can bring about NSSI. However, these effects were also moderated by the EMA. This research expands our understanding of PSR and NSSI in students during the pandemic.


Subject(s)
COVID-19 , Self-Injurious Behavior , Sleep Wake Disorders , COVID-19/epidemiology , China/epidemiology , Female , Humans , Male , Self-Injurious Behavior/epidemiology , Self-Injurious Behavior/etiology , Self-Injurious Behavior/psychology , Sleep Wake Disorders/epidemiology , Stress, Psychological/epidemiology , Students/psychology
7.
Emerg Microbes Infect ; 11(1): 793-803, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1758587

ABSTRACT

The specific antibodies induced by SARS-CoV-2 infection may provide protection against a subsequent infection. However, the efficacy and duration of protection provided by naturally acquired immunity against subsequent SARS-CoV-2 infection remain controversial. We systematically searched for the literature describing COVID-19 reinfection published before 07 February 2022. The outcomes were the pooled incidence rate ratio (IRR) for estimating the risk of subsequent infection. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included studies. Statistical analyses were conducted using the R programming language 4.0.2. We identified 19 eligible studies including more than 3.5 million individuals without the history of COVID-19 vaccination. The efficacy of naturally acquired antibodies against reinfection was estimated at 84% (pooled IRR = 0.16, 95% CI: 0.14-0.18), with higher efficacy against symptomatic COVID-19 cases (pooled IRR = 0.09, 95% CI = 0.07-0.12) than asymptomatic infection (pooled IRR = 0.28, 95% CI = 0.14-0.54). In the subgroup analyses, the pooled IRRs of COVID-19 infection in health care workers (HCWs) and the general population were 0.22 (95% CI = 0.16-0.31) and 0.14 (95% CI = 0.12-0.17), respectively, with a significant difference (P = 0.02), and those in older (over 60 years) and younger (under 60 years) populations were 0.26 (95% CI = 0.15-0.48) and 0.16 (95% CI = 0.14-0.19), respectively. The risk of subsequent infection in the seropositive population appeared to increase slowly over time. In conclusion, naturally acquired antibodies against SARS-CoV-2 can significantly reduce the risk of subsequent infection, with a protection efficacy of 84%.Registration number: CRD42021286222.


Subject(s)
COVID-19 , Aged , Asymptomatic Infections , COVID-19/prevention & control , COVID-19 Vaccines , Health Personnel , Humans , SARS-CoV-2
8.
J Med Virol ; 2022 Mar 23.
Article in English | MEDLINE | ID: covidwho-1756617

ABSTRACT

SARS-CoV-2 has evolved into a panel of variants of concern (VOCs) and constituted a sustained threat to global health. The wildtype (WT) SARS-CoV-2 isolates fail to infect mice, while the Beta variant, one of the VOCs, has acquired the capability to infect standard laboratory mice, raising a spreading risk of SARS-CoV-2 from humans to mice. However, the infectivity and pathogenicity of other VOCs in mice remain not fully understood. In this study, we systematically investigated the infectivity and pathogenicity of three VOCs, Alpha, Beta, and Delta, in mice in comparison with two well-understood SARS-CoV-2 mouse-adapted strains, MASCp6 and MASCp36, sharing key mutations in the receptor-binding domain (RBD) with Alpha or Beta, respectively. Our results showed that the Beta variant had the strongest infectivity and pathogenicity among the three VOCs, while the Delta variant only caused limited replication and mild pathogenic changes in the mouse lung, which is much weaker than what the Alpha variant did. Meanwhile, Alpha showed comparable infectivity in lungs in comparison with MASCp6, and Beta only showed slightly lower infectivity in lungs when compared with MASCp36. These results indicated that all three VOCs have acquired the capability to infect mice, highlighting the ongoing spillover risk of SARS-CoV-2 from humans to mice during the continued evolution of SARS-CoV-2, and that the key amino acid mutations in the RBD of mouse-adapted strains may be referenced as an early-warning indicator for predicting the spillover risk of newly emerging SARS-CoV-2 variants.

9.
Frontiers in microbiology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1733475

ABSTRACT

The coronavirus disease 2019 (COVID-19) vaccines have very successfully decreased the disease risk as we know;some key information remains unknown due to the short development history and the lack of long-term follow-up studies in vaccinated populations. One of the unanswered issues is the protection duration conferred after COVID-19 vaccination, which appears to play a pivotal role in the future impact of pathogens and is critical to inform the public health response and policy decisions. Here, we review current information on the long-term effectiveness of different COVID-19 vaccines, persistence of immunogenicity, and gaps in knowledge. Meanwhile, we also discuss the influencing factors and future study prospects on this topic.

10.
Life (Basel) ; 12(3)2022 Feb 24.
Article in English | MEDLINE | ID: covidwho-1732111

ABSTRACT

BACKGROUND: Related to the SARS-CoV-2 pandemic leading to COVID-19 illness, patients with cancer comorbidity are known to have a higher risk of developing severe viral-related events, including death. To date, there are few treatments with proven efficacy for COVID-19. Vitamin C administered intravenously (IVC) has been extensively investigated in cancer treatment with a known safety profile and has been proposed to play a role in managing COVID-19. IVC was used to treat COVID-19 patients in hospitals in China, USA, and Europe with reported benefits. We report here unexpected beneficial results from the use of IVC in two severely ill oncology patients with documented COVID-19 lung disease. CASE REPORT: two oncology patients were diagnosed with SARS-CoV-2 infection. Prior to receiving IVC, lung infiltrates and systemic inflammation in both patients were progressing despite multiple anti-viral, antibiotic, and anti-inflammatory treatments with intensive supportive care. Both patients subsequently received 12 g of IVC delivered intravenously over 30 min, given 2 times daily for 7 days. Serial SARS-CoV-2 nucleic acid tests showed that the viral load was negative only after the 7-day IVC treatment. In both patients after receiving IVC infusions, imaging by chest CT or X-ray showed improving lung infiltrates. There were reductions in systematic inflammation by high-sensitivity C-reactive protein (hsCRP), and Interleukin-6 (IL-6) testing. No adverse events were observed related to IVC treatment. CONCLUSION: the use of high-dose IVC demonstrated unexpected clinical benefits in treating COVID-19 in two cancer patients presenting with complicated severe comorbidities where an unfavorable prognosis was anticipated.

11.
Innovation (N Y) ; 3(2): 100221, 2022 Mar 29.
Article in English | MEDLINE | ID: covidwho-1713028

ABSTRACT

The highly pathogenic and readily transmissible SARS-CoV-2 has caused a global coronavirus pandemic, urgently requiring effective countermeasures against its rapid expansion. All available vaccine platforms are being used to generate safe and effective COVID-19 vaccines. Here, we generated a live-attenuated candidate vaccine strain by serial passaging of a SARS-CoV-2 clinical isolate in Vero cells. Deep sequencing revealed the dynamic adaptation of SARS-CoV-2 in Vero cells, resulting in a stable clone with a deletion of seven amino acids (N679SPRRAR685) at the S1/S2 junction of the S protein (named VAS5). VAS5 showed significant attenuation of replication in multiple human cell lines, human airway epithelium organoids, and hACE2 mice. Viral fitness competition assays demonstrated that VAS5 showed specific tropism to Vero cells but decreased fitness in human cells compared with the parental virus. More importantly, a single intranasal injection of VAS5 elicited a high level of neutralizing antibodies and prevented SARS-CoV-2 infection in mice as well as close-contact transmission in golden Syrian hamsters. Structural and biochemical analysis revealed a stable and locked prefusion conformation of the S trimer of VAS5, which most resembles SARS-CoV-2-3Q-2P, an advanced vaccine immunogen (NVAX-CoV2373). Further systematic antigenic profiling and immunogenicity validation confirmed that the VAS5 S trimer presents an enhanced antigenic mimic of the wild-type S trimer. Our results not only provide a potent live-attenuated vaccine candidate against COVID-19 but also clarify the molecular and structural basis for the highly attenuated and super immunogenic phenotype of VAS5.

12.
Cell Res ; 32(4): 375-382, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1707327

ABSTRACT

Monoclonal antibodies represent important weapons in our arsenal to against the COVID-19 pandemic. However, this potential is severely limited by the time-consuming process of developing effective antibodies and the relative high cost of manufacturing. Herein, we present a rapid and cost-effective lipid nanoparticle (LNP) encapsulated-mRNA platform for in vivo delivery of SARS-CoV-2 neutralization antibodies. Two mRNAs encoding the light and heavy chains of a potent SARS-CoV-2 neutralizing antibody HB27, which is currently being evaluated in clinical trials, were encapsulated into clinical grade LNP formulations (named as mRNA-HB27-LNP). In vivo characterization demonstrated that intravenous administration of mRNA-HB27-LNP in mice resulted in a longer circulating half-life compared with the original HB27 antibody in protein format. More importantly, a single prophylactic administration of mRNA-HB27-LNP provided protection against SARS-CoV-2 challenge in mice at 1, 7 and even 63 days post administration. In a close contact transmission model, prophylactic administration of mRNA-HB27-LNP prevented SARS-CoV-2 infection between hamsters in a dose-dependent manner. Overall, our results demonstrate a superior long-term protection against SARS-CoV-2 conferred by a single administration of this unique mRNA antibody, highlighting the potential of this universal platform for antibody-based disease prevention and therapy against COVID-19 as well as a variety of other infectious diseases.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/therapeutic use , COVID-19/prevention & control , Cricetinae , Humans , Liposomes , Mice , Nanoparticles , Pandemics/prevention & control , RNA, Messenger/genetics , Spike Glycoprotein, Coronavirus
13.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325078

ABSTRACT

The epidemic of Coronavirus Disease 2019 (Covid-19) has brought many changes to people's life. This study aims to analysis Chinese people's psychological change and life after quarantining Wuhan and explore the influencing factors. Based on data from a web-survey after quarantining Wuhan (N=3268), the principal-component-analysis (PCA), multiple-linear-regression (MLR), propensity-score-matching (PSM) were used to explore the psychological change of people in China and the influencing factors. 83.3% of the respondents said that the impact of the epidemic on their life had increased after quarantining Wuhan. A considerable proportion of people's anxiety increased, being reflected in negative emotion, behavioral response and physiological response. The proportion of people who said their anxiety had increased in Wuhan was higher than that in other regions (p <0.05). The anxiety of people who were in medical isolation increased less than those who were not (p <0.05). All three aspects of people’s anxiety were positively related with time of medical isolation and degree of the attention on the epidemic (p<0.05) except the effect of attention degree on the physiological response (p=0.06). The measure of medical isolation at home should be advocated. Yet people should reduce the concern for the epidemic while paying attention to self-protection.

14.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308248

ABSTRACT

Background: The aim of this study was to survey the general public in China to better understand their levels of psychological state and its influencing factors after the Wuhan shutdown on 23 Jan. Methods: : A survey was conducted on Feb 20-24, using an online self-administrated questionnaire among 4071 participants. Data on subjective indicators of daily-life change was collected, and individual scores on changes in anxiety, depression, and stress were generated by 8-item, 11-item, and 6-item questions. After bivariate analyses, multiple linear regression analyses were conducted to investigate independent associations between socio-demographic variables, subjective indicators of changes in daily life, and summary scores including anxiety, depression, and stress scores. Results: : Information from 3803 participants was available for analysis. Multivariable regression analyses showed that the anxiety (B=-1.27, 95%CI=-1.71 to -0.82), depression (B=-1.47, 95%CI=-2.06 to -0.88), and stress (B=-0.79, 95%CI=-1.13 to -0.46) scores of people in rural areas are lower than those in urban areas. People living in the other regions except Hubei, higher education were independent correlates of less negative emotions, while people with relatively high incomes had poor psychological status in anxiety (B=0.73, 95%CI=0.08 to 1.38),depression (B=1.45, 95%CI=0.60 to 2.30) and stress (B=0.65, 95%CI=0.17 to 1.13). Married people were less anxious (B=-0.67, 95%CI=-1.30 to -0.05), depressed (B=-1.14, 95%CI=-1.96 to -0.33), and stressed (B=-0.47, 95%CI=-0.93 to 0.00) than single people. The level of attention, self-assessed infection risk, impact of the daily life and mental-health help-seeking tended to be positively associated with the scores of anxiety, depression, and stress (p<0.001). Conclusions: : Usual residence, education, marital status, monthly income, the level of attention, self-assessed infection risk, impact of the daily life and mental-health help-seeking are important correlates of the scores of anxiety, depression, and stress. Awareness of these relevant factors could help the government and related personnel to prevent more severe psychological trauma in the later period.

15.
Epidemiology and infection ; 149, 2021.
Article in English | EuropePMC | ID: covidwho-1609638

ABSTRACT

The article aims to estimate and forecast the transmissibility of shigellosis and explore the association of meteorological factors with shigellosis. The mathematical model named Susceptible–Exposed–Symptomatic/Asymptomatic–Recovered–Water/Food (SEIARW) was used to explore the feature of shigellosis transmission based on the data of Wuhan City, China, from 2005 to 2017. The study applied effective reproduction number (Reff) to estimate the transmissibility. Daily meteorological data from 2008 to 2017 were used to determine Spearman's correlation with reported new cases and Reff. The SEIARW model fit the data well (χ2 = 0.00046, p > 0.999). The simulation results showed that the reservoir-to-person transmission of the shigellosis route has been interrupted. The Reff would be reduced to a transmission threshold of 1.00 (95% confidence interval (CI) 0.82–1.19) in 2035. Reducing the infectious period to 11.25 days would also decrease the value of Reff to 0.99. There was a significant correlation between new cases of shigellosis and atmospheric pressure, temperature, wind speed and sun hours per day. The correlation coefficients, although statistically significant, were very low (<0.3). In Wuhan, China, the main transmission pattern of shigellosis is person-to-person. Meteorological factors, especially daily atmospheric pressure and temperature, may influence the epidemic of shigellosis.

16.
J Virol ; 96(1): e0125321, 2022 01 12.
Article in English | MEDLINE | ID: covidwho-1639525

ABSTRACT

Over the past 20 years, the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV), and SARS-CoV-2 emerged, causing severe human respiratory diseases throughout the globe. Developing broad-spectrum drugs would be invaluable in responding to new, emerging coronaviruses and to address unmet urgent clinical needs. Main protease (Mpro; also known as 3CLpro) has a major role in the coronavirus life cycle and is one of the most important targets for anti-coronavirus agents. We show that a natural product, noncovalent inhibitor, shikonin, is a pan-main protease inhibitor of SARS-CoV-2, SARS-CoV, MERS-CoV, human coronavirus (HCoV)-HKU1, HCoV-NL63, and HCoV-229E with micromolar half maximal inhibitory concentration (IC50) values. Structures of the main protease of different coronavirus genus, SARS-CoV from the betacoronavirus genus and HCoV-NL63 from the alphacoronavirus genus, were determined by X-ray crystallography and revealed that the inhibitor interacts with key active site residues in a unique mode. The structure of the main protease inhibitor complex presents an opportunity to discover a novel series of broad-spectrum inhibitors. These data provide substantial evidence that shikonin and its derivatives may be effective against most coronaviruses as well as emerging coronaviruses of the future. Given the importance of the main protease for coronavirus therapeutic indication, insights from these studies should accelerate the development and design of safer and more effective antiviral agents. IMPORTANCE The current pandemic has created an urgent need for broad-spectrum inhibitors of SARS-CoV-2. The main protease is relatively conservative compared to the spike protein and, thus, is one of the most promising targets in developing anti-coronavirus agents. We solved the crystal structures of the main protease of SARS-CoV and HCoV-NL63 that bound to shikonin. The structures provide important insights, have broad implications for understanding the structural basis underlying enzyme activity, and can facilitate rational design of broad-spectrum anti-coronavirus ligands as new therapeutic agents.


Subject(s)
Antiviral Agents/chemistry , Coronavirus 3C Proteases/antagonists & inhibitors , Protease Inhibitors/chemistry , Catalytic Domain , Coronavirus/classification , Coronavirus/enzymology , Coronavirus 3C Proteases/chemistry , Crystallography, X-Ray , Molecular Docking Simulation , Naphthoquinones/chemistry , Protein Binding
17.
Nat Metab ; 4(1): 29-43, 2022 01.
Article in English | MEDLINE | ID: covidwho-1612214

ABSTRACT

Severe cases of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with elevated blood glucose levels and metabolic complications. However, the molecular mechanisms for how SARS-CoV-2 infection alters glycometabolic control are incompletely understood. Here, we connect the circulating protein GP73 with enhanced hepatic gluconeogenesis during SARS-CoV-2 infection. We first demonstrate that GP73 secretion is induced in multiple tissues upon fasting and that GP73 stimulates hepatic gluconeogenesis through the cAMP/PKA signaling pathway. We further show that GP73 secretion is increased in cultured cells infected with SARS-CoV-2, after overexpression of SARS-CoV-2 nucleocapsid and spike proteins and in lungs and livers of mice infected with a mouse-adapted SARS-CoV-2 strain. GP73 blockade with an antibody inhibits excessive glucogenesis stimulated by SARS-CoV-2 in vitro and lowers elevated fasting blood glucose levels in infected mice. In patients with COVID-19, plasma GP73 levels are elevated and positively correlate with blood glucose levels. Our data suggest that GP73 is a glucogenic hormone that likely contributes to SARS-CoV-2-induced abnormalities in systemic glucose metabolism.


Subject(s)
COVID-19/complications , COVID-19/virology , Glucose/metabolism , Hyperglycemia/etiology , Hyperglycemia/metabolism , Membrane Proteins/metabolism , SARS-CoV-2 , Animals , Biomarkers , Cyclic AMP-Dependent Protein Kinases/metabolism , Diet, High-Fat , Disease Models, Animal , Fasting , Gene Expression , Gluconeogenesis/drug effects , Gluconeogenesis/genetics , Host-Pathogen Interactions , Humans , Hyperglycemia/blood , Liver/metabolism , Liver/pathology , Membrane Proteins/antagonists & inhibitors , Membrane Proteins/blood , Membrane Proteins/genetics , Mice , Mice, Knockout , Organ Specificity/genetics
20.
Preprint in English | bioRxiv | ID: ppbiorxiv-471198

ABSTRACT

Viral vaccines can lose their efficacy as the genomes of targeted viruses rapidly evolve, resulting in new variants that may evade vaccine-induced immunity. This process is apparent in the emergence of new SARS-CoV-2 variants which have the potential to undermine vaccination efforts and cause further outbreaks. Predictive vaccinology points to a future of pandemic preparedness in which vaccines can be developed preemptively based in part on predictive models of viral evolution. Thus, modeling the trajectory of SARS-CoV-2 spike protein evolution could have value for mRNA vaccine development. Traditionally, in silico sequence evolution has been modeled discretely, while there has been limited investigation into continuous models. Here we present the Viral Predictor for mRNA Evolution (VPRE), an open-source software tool which learns from mutational patterns in viral proteins and models their most statistically likely evolutionary trajectories. We trained a variational autoencoder with real-time and simulated SARS-CoV-2 genome data from Australia to encode discrete spike protein sequences into continuous numerical variables. To simulate evolution along a phylogenetic path, we trained a Gaussian process model with the numerical variables to project spike protein evolution up to five months in advance. Our predictions mapped primarily to a sequence that differed by a single amino acid from the most reported spike protein in Australia within the prediction timeframe, indicating the utility of deep learning and continuous latent spaces for modeling viral protein evolution. VPRE can be readily adapted to investigate and predict the evolution of viruses other than SARS-CoV-2 in temporal, geographic, and lineage-specific pathways.

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