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1.
Economic Geography ; : 1-27, 2022.
Article in English | Academic Search Complete | ID: covidwho-1921885

ABSTRACT

Breakthroughs in biotechnology, globalizing intellectual property rights legislations, and growing venture capital in the past thirty years have given rise to new forms of capitalist accumulation that scholars called biocapitalism. Bioscientific knowledge under biocapitalism is increasingly parceled out from a global common to private enclosures for biotech and pharmaceutical companies, contributing to vast inequalities and fractures of global access to innovation evident in the COVID-19 pandemic. The assetization and financialization of knowledge have shifted the ground of innovation from competitive commodity production and exchanges to generating, managing, and commercializing patents and associated monopoly rights, thus raising the challenges of innovation for those developing countries specialized in production. Many Asian countries have invested heavily in biomedical sciences to enhance their knowledge assets but had limited success in translating the scientific development to a globally significant biomedical industry. This article discusses the evolution of China’s biomedical industry from a technological laggard to a recent innovation boom after a regulatory overhaul in 2015. Analyzing the patent collaborative networks of China’s biomedical industry since 2003, we found the central roles of domestic public research institutions, in contrast to multinational corporations, as cutting-edge knowledge providers. We argue that China’s path of the biomedical industry is distinct from its other technology industries that rely on multinational corporations for core knowledge. It represents a national articulation in response to global biocapitalism by situating the domestic research institutions and biomedical firms at the center of knowledge assets production and engaging globally in the science and drug regulatory systems. [ FROM AUTHOR] Copyright of Economic Geography is the property of Taylor & Francis Ltd 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.)

2.
Sci China Life Sci ; 65(7): 1285-1324, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1899275

ABSTRACT

RNA structures are essential to support RNA functions and regulation in various biological processes. Recently, a range of novel technologies have been developed to decode genome-wide RNA structures and novel modes of functionality across a wide range of species. In this review, we summarize key strategies for probing the RNA structurome and discuss the pros and cons of representative technologies. In particular, these new technologies have been applied to dissect the structural landscape of the SARS-CoV-2 RNA genome. We also summarize the functionalities of RNA structures discovered in different regulatory layers-including RNA processing, transport, localization, and mRNA translation-across viruses, bacteria, animals, and plants. We review many versatile RNA structural elements in the context of different physiological and pathological processes (e.g., cell differentiation, stress response, and viral replication). Finally, we discuss future prospects for RNA structural studies to map the RNA structurome at higher resolution and at the single-molecule and single-cell level, and to decipher novel modes of RNA structures and functions for innovative applications.


Subject(s)
COVID-19 , RNA , Animals , Nucleic Acid Conformation , RNA/chemistry , RNA/genetics , RNA, Viral/genetics , SARS-CoV-2/genetics , Sequence Analysis, RNA
3.
Inorganica Chimica Acta ; 539:121027, 2022.
Article in English | ScienceDirect | ID: covidwho-1851180

ABSTRACT

HIV-1 reverse transcriptase (RT) inhibitors play essential role in anti-HIV therapy. The vast majority of them target the enzymes, while very few are able to bind to the viral RNA. Here we designed and synthesized two new terpyridyl Ru(II) complexes with HIV-1 TAR RNA binding groups. The complex RuTz2 exhibited a remarkable selectivity for poly(A) RNA over calf thymus DNA, total RNA and yeast transfer RNA, generated significant visible spectral response and inhibited the reverse transcription of poly(A) RNA to poly(dT) cDNA by M-MuLV RT. Moreover, RuTz2 was found to target the HIV-1 TAR RNA tightly and selectively by molecular recognition of hydrogen bonds, further stabilize the Ru(II)-RNA binding complex by electrostatic attraction, and efficiently inhibit the HIV-1 RT. These terpyridyl Ru(II) complexes also showed low toxicity to normal cells, which would greatly reduce its harmful side-effect on normal cells in drug application. This work also provides valuable drug design strategies for AIDS and other RT related diseases researches, such as HCV, EBOV and SARS-CoV-2.

4.
Acta Psychol (Amst) ; 226: 103571, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1813997

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is profoundly affecting lives around the globe. Previous studies on COVID-19 mainly focused on epidemiological, clinical, and radiological features of patients with confirmed infection. Little attention has been paid to the follow-up of recovered patients. As a vulnerable population to adverse events, the health status of the COVID-19 recovered pediatric patients is of great concern. We aimed to investigate the prevalence of behavioral problems among pediatric patients recovered from the COVID-19 in Wuhan, China. METHODS: A total of 122 children who were suspected or confirmed COVID-19 cases and hospitalized for treatment were enrolled in the study between April 2020 and May 2020 in Wuhan, China. We collected related information about hospitalization and discharge of the children and emotional symptoms of their parents through electronic medical records and questionnaire. The behavioral problems of children were examined by applying the parent-reported the Strengths and Difficulties Questionnaire (SDQ). RESULTS: The participant children were discharged from hospital after about two months. Among them, 76 (62%) were boys, and the mean age was 6.71 years old. The highest prevalence of behavioral problems among pediatric children with COVID-19 was for prosocial behavior (15%), followed by total difficulties (13%), emotional symptoms (11%), hyperactivity (10%), conduct problems (9%), and peer problems (1%). With regarding to their parents, 26% reported having symptoms of anxiety and 23% as having symptoms of depression. The scores of SDQ were higher in those children whose parents have emotional problems compared to parents without. CONCLUSION: Long-term follow up studies on the psychological and behavioral problems of COVID-19 recovered children and their parents are warranted.


Subject(s)
COVID-19 , Problem Behavior , Anxiety/epidemiology , Child , China/epidemiology , Female , Humans , Male , Problem Behavior/psychology , Surveys and Questionnaires
5.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-332344

ABSTRACT

Background: Care patterns and TCM constitution affects systemic scleroderma (SSc) patients’ emotion and health while the prevalence of covid-19 may aggravate this situation. Thus, we investigated depression and anxiety level in SSc patients during the COVID-19 pandemic to identify the correlation between care patterns, TCM constitution and patients' emotion. Methods: : This was a cross-sectional study. SSc patients and healthy individuals were surveyed through the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, the Constitution in Chinese Medicine Questionnaire and a modified care pattern questionnaire. Factors correlated with depression and anxiety were screened by univariate and multivariate logistic regression. Results: : A total of 273 SSc patients and 111 healthy individuals were included. The median age was 45 years in both patient and healthy groups. 74.36% of SSc patients were in depression and 51.65% were in anxiety. 69.60% worked remotely and 50.92% experienced a decrease in income, which were both higher than in the healthy group (38.74%, 29.73%). The proportion of income reduction in the online group (56.19%) was higher than that in the hospital group (33.33%) (P = 0.001). 36.99% of SSc patients had disease progression during the pandemic. Yang-deficiency constitution (82.05%) was the TCM constitution characteristic of SSc patients, while Qi-deficiency(73.63%) and Blood-stasis constitution (57.14%) were also more common. TCM constitution of patients from different sources distributed roughly similar. Qi-deficiency (adjusted OR=2.250) and Qi-stagnation (adjusted OR= 3.824) constitution were significantly associated with depression. The major constitution of dampness-heat was associated with a decrease in depression (adjusted OR=0.160). Remote work during the outbreak (adjusted OR= 1.920), decreasing in income (adjusted OR=3.556), and disease progression (P=0.030) were associated with the occurrence of depression. Conclusion: Chinese SSc patients have a high prevalence of depression and anxiety. The COVID-19 pandemic has changed the care patterns of Chinese SSc patients in terms of work, income, and ways of getting medical support. Within the care patterns, work, income, disease and change of medications were correlates of depression or anxiety in SSc patients. Qi-stagnation and Qi-deficiency constitution were associated with depression, and Qi-stagnation constitution was associated with anxiety in SSc patients. Further research is needed. Trial registration: ChiCTR, ChiCTR2000038796, Registered 02 October 2020, http://www.chictr.org.cn/showproj.aspx?proj=62301

6.
Front Public Health ; 9: 734370, 2021.
Article in English | MEDLINE | ID: covidwho-1775872

ABSTRACT

Neurophysiological effect of human exposure to radiofrequency signals has attracted considerable attention, which was claimed to have an association with a series of clinical symptoms. A few investigations have been conducted on alteration of brain functions, yet no known research focused on intrinsic connectivity networks, an attribute that may relate to some behavioral functions. To investigate the exposure effect on functional connectivity between intrinsic connectivity networks, we conducted experiments with seventeen participants experiencing localized head exposure to real and sham time-division long-term evolution signal for 30 min. The resting-state functional magnetic resonance imaging data were collected before and after exposure, respectively. Group-level independent component analysis was used to decompose networks of interest. Three states were clustered, which can reflect different cognitive conditions. Dynamic connectivity as well as conventional connectivity between networks per state were computed and followed by paired sample t-tests. Results showed that there was no statistical difference in static or dynamic functional network connectivity in both real and sham exposure conditions, and pointed out that the impact of short-term electromagnetic exposure was undetected at the ICNs level. The specific brain parcellations and metrics used in the study may lead to different results on brain modulation.


Subject(s)
Brain Mapping , Brain/diagnostic imaging , Brain/physiology , Communication , Humans , Magnetic Resonance Imaging/methods , Pilot Projects
7.
Front Pharmacol ; 13: 833679, 2022.
Article in English | MEDLINE | ID: covidwho-1775747

ABSTRACT

Background: The information is relatively scarce regarding the occurrence of drug-induced acute kidney injury (AKI) when anti-coronavirus disease 2019 (COVID-19) drugs are prescribed for patients with diabetes mellitus (DM). Objective: The objective of this study was to evaluate a pharmacovigilance signal for AKI upon the use of common drugs prescribed for COVID-19 treatment, especially in patients with DM. Methods: The FDA Adverse Event Reporting System (FAERS) database were used, and data from the first quarter of 2020 to the third quarter of 2021 were retrieved. A disproportionality analysis was performed to determine whether AKI was more frequently reported with anti-COVID-19 drugs compared to that with other drugs in different populations. Further, reporting odds ratios (RORs) and their 95% confidence intervals (CIs) were used to calculate disproportionality. Results: We identified 33,488 COVID-19 patients and 2397 COVID-19 patients with DM. AKI was the most frequent adverse drug reaction (ADR) reported in this patient population. The primary suspected drugs related to AKI in more than half of the reports (75.60%, 127/168) were four common anti-COVID-19 drugs (remdesivir, tocilizumab, hydroxychloroquine, and lopinavir/ritonavir). Compared with other drugs in the same time window, remdesivir and lopinavir/ritonavir were associated with an increased risk of AKI in all COVID-19 patients (ROR: 3.97, 95% CI: 3.51-4.50; ROR: 4.02, 95% CI: 3.11-5.19, respectively). In COVID-19 patients with DM, remdesivir was significantly associated with AKI (ROR: 5.65, 95% CI: 4.06-7.87); meanwhile, there was a new AKI signal associated with tocilizumab (ROR: 2.37, 95% CI: 1.19-4.72). After sensitivity analyses in COVID-19 patients with DM, consistent results for remdesivir were observed; however, the AKI signals for tocilizumab were unstable. Conclusion: Our study confirmed the association of AKI with the usage of common anti-COVID-19 drugs (especially remdesivir and tocilizumab) in DM patients. These safety signals suggested more individualized treatments for COVID-19 patients with comorbidities. Cross-disciplinary collaborative is needed to improve current strategy of clinical treatment and develop new approaches to management.

8.
Signal Transduct Target Ther ; 7(1): 112, 2022 04 02.
Article in English | MEDLINE | ID: covidwho-1773956

ABSTRACT

Critical coronavirus disease 2019 (COVID-19) is associated with high mortality and potential genetic factors have been reported to be involved in the development of critical COVID-19. We performed a genome-wide association study to identify the genetic factors responsible for developing critical COVID-19. 632 critical patients with COVID-19 and 3021 healthy controls from the Chinese population were recruited. First, we identified a genome-wide significant difference of IL-6 rs2069837 (p = 9.73 × 10-15, OR = 0.41) between 437 critical patients with COVID-19 and 2551 normal controls in the discovery cohort. When replicated these findings in a set of 195 patients with critical COVID-19 and 470 healthy controls, we detected significant association of rs2069837 with COVID-19 (p = 8.89 × 10-3, OR = 0.67). This variant surpassed the formal threshold for genome-wide significance (combined p = 4.64 × 10-16, OR = 0.49). Further analysis revealed that there was a significantly stronger expression of IL-6 in the serum from patients with critical COVID-19 than in that from patients with asymptomatic COVID-19. An in vitro assay showed that the A to G allele changes in rs2069837 within IL-6 obviously decreased the luciferase expression activity. When analyzing the effect of this variant on the IL-6 in the serum based on the rs2069837 genotype, we found that the A to G variation in rs2069837 decreased the expression of IL-6, especially in the male. Overall, we identified a genetic variant in IL-6 that protects against critical conditions with COVID-19 though decreasing IL-6 expression in the serum.


Subject(s)
COVID-19 , Interleukin-6/genetics , COVID-19/genetics , Genetic Predisposition to Disease/genetics , Genome-Wide Association Study , Humans , Male , Polymorphism, Single Nucleotide/genetics
9.
Acta psychologica ; 2022.
Article in English | EuropePMC | ID: covidwho-1749830

ABSTRACT

Background Coronavirus disease 2019 (COVID-19) is profoundly affecting lives around the globe. Previous studies on COVID-19 mainly focused on epidemiological, clinical, and radiological features of patients with confirmed infection. Little attention has been paid to the follow-up of recovered patients. As a vulnerable population to adverse events, the health status of the COVID-19 recovered pediatric patients is of great concern. We aimed to investigate the prevalence of behavioral problems among pediatric patients recovered from the COVID-19 in Wuhan, China. Methods A total of 122 children who were suspected or confirmed COVID-19 cases and hospitalized for treatment were enrolled in the study between April 2020 and May 2020 in Wuhan, China. We collected related information about hospitalization and discharge of the children and emotional symptoms of their parents through electronic medical records and questionnaire. The behavioral problems of children were examined by applying the parent-reported the Strengths and Difficulties Questionnaire (SDQ). Results The participant children were discharged from hospital after about two months. Among them, 76 (62%) were boys, and the mean age was 6.71 years old. The highest prevalence of behavioral problems among pediatric children with COVID-19 was for prosocial behavior (15%), followed by total difficulties (13%), emotional symptoms (11%), hyperactivity (10%), conduct problems (9%), and peer problems (1%). With regarding to their parents, 26% reported having symptoms of anxiety and 23% as having symptoms of depression. The scores of SDQ were higher in those children whose parents have emotional problems compared to parents without. Conclusion Long-term follow up studies on the psychological and behavioral problems of COVID-19 recovered children and their parents are warranted.

10.
mBio ; : e0366221, 2022 Jan 25.
Article in English | MEDLINE | ID: covidwho-1741579

ABSTRACT

The ongoing coronavirus (CoV) disease 2019 (COVID-19) pandemic caused by infection with severe acute respiratory syndrome CoV 2 (SARS-CoV-2) is associated with substantial morbidity and mortality. Understanding the immunological and pathological processes of coronavirus diseases is crucial for the rational design of effective vaccines and therapies for COVID-19. Previous studies showed that 2'-O-methylation of the viral RNA cap structure is required to prevent the recognition of viral RNAs by intracellular innate sensors. Here, we demonstrate that the guanine N7-methylation of the 5' cap mediated by coronavirus nonstructural protein 14 (nsp14) contributes to viral evasion of the type I interferon (IFN-I)-mediated immune response and pathogenesis in mice. A Y414A substitution in nsp14 of the coronavirus mouse hepatitis virus (MHV) significantly decreased N7-methyltransferase activity and reduced guanine N7-methylation of the 5' cap in vitro. Infection of myeloid cells with recombinant MHV harboring the nsp14-Y414A mutation (rMHVnsp14-Y414A) resulted in upregulated expression of IFN-I and ISG15 mainly via MDA5 signaling and in reduced viral replication compared to that of wild-type rMHV. rMHVnsp14-Y414A replicated to lower titers in livers and brains and exhibited an attenuated phenotype in mice. This attenuated phenotype was IFN-I dependent because the virulence of the rMHVnsp14-Y414A mutant was restored in Ifnar-/- mice. We further found that the comparable mutation (Y420A) in SARS-CoV-2 nsp14 (rSARS-CoV-2nsp14-Y420A) also significantly decreased N7-methyltransferase activity in vitro, and the mutant virus was attenuated in K18-human ACE2 transgenic mice. Moreover, infection with rSARS-CoV-2nsp14-Y420A conferred complete protection against subsequent and otherwise lethal SARS-CoV-2 infection in mice, indicating the vaccine potential of this mutant. IMPORTANCE Coronaviruses (CoVs), including SARS-CoV-2, the cause of COVID-19, use several strategies to evade the host innate immune responses. While the cap structure of RNA, including CoV RNA, is important for translation, previous studies indicate that the cap also contributes to viral evasion from the host immune response. In this study, we demonstrate that the N7-methylated cap structure of CoV RNA is pivotal for virus immunoevasion. Using recombinant MHV and SARS-CoV-2 encoding an inactive N7-methyltransferase, we demonstrate that these mutant viruses are highly attenuated in vivo and that attenuation is apparent at very early times after infection. Virulence is restored in mice lacking interferon signaling. Further, we show that infection with virus defective in N7-methylation protects mice from lethal SARS-CoV-2, suggesting that the N7-methylase might be a useful target in drug and vaccine development.

11.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329378

ABSTRACT

Objective: To clarify the accuracy of clusters of regularly spaced short palindrome repeats (CRISPR) technology and chest CT in the diagnosis of Corona Virus Disease2019(COVID-19). Methods: The term "Corona Virus Disease " "clustered regularly spaced short palindromic repeats" "CRISPR", "chest CT", "sensitivity and specificity" as the subject words or keywords were searched in databases such as Pubmed, Embase, Cochrane Library, Wiley and Scopus and Chinese academic databases (such as CNKI, Wanfang and Chongqing VIP data) for relevant literature on the use of CRISPR technology and chest CT for the diagnosis of COVID-19. Meta-analysis was performed after literature screening, quality assessment and data extraction . Results: A total of 418 articles were retrieved, and 17 articles were finally included. The results showed that the combined sensitivity of CRISPR technology for diagnosing new coronary pneumonia infection was 0.96 [95% CI (0.93, 0.98)], and the combined specificity was 1.00 [95% CI (0.92, 1.00)], the combined positive likelihood ratio is 458.69 [95%CI (11.51, 18280.8)], the combined negative likelihood ratio is 0.04 [95% CI (0.02, 0.07)], the area under the SROC curve is 0.99 [95%CI(0.97,0.99)]. The combined sensitivity of chest CT in diagnosing new coronary pneumonia infection was 0.94 [95%CI (0.83, 0.98)], combined specificity was 0.55 [95% CI (0.22, 0.83)], combined diagnostic odds ratio was 19.90 [95% CI (7.88, 50.25)], the combined positive likelihood ratio is 2.08 [95%CI (1.00, 4.32)], the combined negative likelihood ratio is 0.10 [95% CI (0.05, 0.23)], the area under the SROC curve is 0.91 [95% CI (0.88, 0.93)]. The Deek funnel chart indicates that there is no potential publication bias among the included studies (PCRISPR = 0.03, P chest CT = 0.55). Conclusion: CRISPR technology has a better ability to detect infections in patients with COVID-19, and is better than chest CT in disease diagnosis. CRISPR technology, especially non-SHERLOCK type and multi-target gene detection, can be used to diagnose COVID-19 with higher accuracy ,and can be used for large-scale population screening.

12.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325028

ABSTRACT

Background: Due to the emergency pandemic threat, the COVID-19 has attracted widespread attention around the world. Common symptoms of infection were fever, cough, and myalgia fatigue. On January 31, 2020, the World Health Organization (WHO) declares this outbreak a Public Health Emergency of International Concern (PHEIC). Methods: In order to study the spread of the novel coronavirus pneumonia, this paper proposed an improved SEIR model to simulate the spread of the virus, which includes the effect factor of government intervention. The model parameters are determined based on the daily reported statistical data (up to February 8) of confirmed, suspected, cured, and death. According to utilize the spread rate, the probability of infection of the suspected, the probability of the suspected becoming a confirmed one, the cure rate, the mortality rate, and the quarantine ratio, we performed simulations and parameter calibrations at three region levels, i.e., China, Hubei and non-Hubei respectively. In addition, considering that the government initiated effective prevention and control measures after the outbreak, this paper dynamically estimates all the parameters of the proposed model. Results: The simulation reveals that the parameters of non-Hubei region are not significantly different from Hubei’s. Hubei Province has a high transmission rate, low cure rate, high probability of infection, low effective quarantine rate. since January 31, with the continuous strengthening of epidemic prevention and control measures, all parameters of the model have changed significantly. The parameters of Hubei and non-Hubei regions have the same trend. The trend of all parameters is now moving in a direction that is conducive to reducing the number of confirmed, suspected and fatal cases. Conclusions: The number of infections of the virus initially showed a rapid increase in the trend, and the number of infectious case showed a clear downward shape. With the government to take a variety of prevention and control measures and the efforts of the general medical staff, the number of infection curve on February 22 appeared in the top of the arc pattern, indicating that the inflection point began to appear, but the decline in the number of infections slowly.

13.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324233

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) is profoundly affecting lives around the globe, and up to now, a large of patients have clinically recovered from their initial illness. As the vulnerable population to adverse events, the effect of the COVID-19 outbreak on pediatric recovered patients are of great concern, but relevant researches are limited. We aimed to investigate the prevalence of behavioral problems among pediatric patients with COVID-19 infection after discharge. Methods: : A total of 122 children who were suspected or confirmed COVID-19 cases and hospitalized for treatment were enrolled in the study between April 2020 and May 2020 in Wuhan, China. We collected related information about hospitalization and discharge for the children and emotional symptoms for their parents through electronic medical records and questionnaire. The behavioral problems for children were examined applying the parent-reported the Strengths and Difficulties Questionnaire (SDQ). Results: The participant children were discharged from hospital for about two months. Among them, 76 (62%) were boys, and the mean age were 6.71 years old. The highest prevalence of behavioral problems among pediatric children with COVID-19 was 15% (prosocial behavior), followed by 13% (total difficulties), 11% (emotional symptoms), 10% (hyperactivity), 9% (conduct problems), and 1% (peer problems). With regarding to their parents, 26% of them reported having anxiety symptoms and 23% having depression symptoms. Compared with children without anxious or depressive parents, the scores of SDQ were higher in children whose parents have emotional problems. Conclusions: : The long-term follow up studies on the psychological and behavioral problems of children infected with COVID-19 and their parents are warranted.

14.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-310982

ABSTRACT

This paper investigates the role of job characteristics on an individual's decisions to self-isolate, work, and apply for unemployment insurance in the US during the COVID-19 pandemic. We use data that track millions of mobile devices and their daily movements across physical locations to measure whether the mobile devices leave their homes, or part-time or full-time at work that day, and we also collect data on weekly unemployment insurance claims. We find that the presence of jobs with high work-from-home capacity in a region increases the ability of people to self-isolate and decreases their unemployment risk, whereas the presence of jobs with high physical proximity decreases the incidences of self-isolation and unemployment and increases the incidence of work during the pandemic. These heterogeneous responses based on local job characteristics persist even conditional on a broad set of demographic and socioeconomic variables.

15.
Signal Transduct Target Ther ; 6(1): 438, 2021 12 24.
Article in English | MEDLINE | ID: covidwho-1585880

ABSTRACT

Messenger RNA (mRNA) vaccine technology has shown its power in preventing the ongoing COVID-19 pandemic. Two mRNA vaccines targeting the full-length S protein of SARS-CoV-2 have been authorized for emergency use. Recently, we have developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor-binding domain (RBD) of SARS-CoV-2 (termed ARCoV), which confers complete protection in mouse model. Herein, we further characterized the protection efficacy of ARCoV in nonhuman primates and the long-term stability under normal refrigerator temperature. Intramuscular immunization of two doses of ARCoV elicited robust neutralizing antibodies as well as cellular response against SARS-CoV-2 in cynomolgus macaques. More importantly, ARCoV vaccination in macaques significantly protected animals from acute lung lesions caused by SARS-CoV-2, and viral replication in lungs and secretion in nasal swabs were completely cleared in all animals immunized with low or high doses of ARCoV. No evidence of antibody-dependent enhancement of infection was observed throughout the study. Finally, extensive stability assays showed that ARCoV can be stored at 2-8 °C for at least 6 months without decrease of immunogenicity. All these promising results strongly support the ongoing clinical trial.


Subject(s)
COVID-19 Vaccines/pharmacology , COVID-19/immunology , Immunogenicity, Vaccine , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , /pharmacology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Chlorocebus aethiops , Humans , Macaca fascicularis , Vero Cells , /immunology
16.
Emerg Microbes Infect ; 11(1): 351-367, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1585238

ABSTRACT

The emergence of multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern threatens the efficacy of currently approved vaccines and authorized therapeutic monoclonal antibodies (MAbs). It is hence important to continue searching for SARS-CoV-2 broadly neutralizing MAbs and defining their epitopes. Here, we isolate 9 neutralizing mouse MAbs raised against the spike protein of a SARS-CoV-2 prototype strain and evaluate their neutralizing potency towards a panel of variants, including B.1.1.7, B.1.351, B.1.617.1, and B.1.617.2. By using a combination of biochemical, virological, and cryo-EM structural analyses, we identify three types of cross-variant neutralizing MAbs, represented by S5D2, S5G2, and S3H3, respectively, and further define their epitopes. S5D2 binds the top lateral edge of the receptor-binding motif within the receptor-binding domain (RBD) with a binding footprint centred around the loop477-489, and efficiently neutralizes all variant pseudoviruses, but the potency against B.1.617.2 was observed to decrease significantly. S5G2 targets the highly conserved RBD core region and exhibits comparable neutralization towards the variant panel. S3H3 binds a previously unreported epitope located within the evolutionarily stable SD1 region and is able to near equally neutralize all of the variants tested. Our work thus defines three distinct cross-variant neutralizing sites on the SARS-CoV-2 spike protein, providing guidance for design and development of broadly effective vaccines and MAb-based therapies.


Subject(s)
COVID-19/virology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Epitope Mapping , Female , Humans , Mice , Mice, Inbred BALB C , Neutralization Tests , SARS-CoV-2/chemistry , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
17.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-296266

ABSTRACT

5-Methylcytosine (m 5 C) is a widespread post-transcriptional RNA modification and is reported to be involved in manifold cellular responses and biological processes through regulating RNA metabolism. However, its regulatory role in antiviral innate immunity has not yet been elucidated. Here, we report that NSUN2, a typical m 5 C methyltransferase, can negatively regulate type I interferon responses during viral infection. NSUN2 specifically mediates m 5 C methylation of IRF3 mRNA and accelerates its degradation, resulting in low levels of IRF3 and downstream IFN-β production. Knockout or knockdown of NSUN2 could enhance type I interferon responses and downstream ISG expression after viral infection in vitro . And in vivo , the antiviral innate responses is more dramatically enhanced in Nsun2 +/− mice than in Nsun2 +/+ mice. Four highly m 5 C methylated cytosines in IRF3 mRNA were identified, and their mutation could enhance the cellular IRF3 mRNA levels. Moreover, infection with Sendai virus (SeV), vesicular stomatitis virus (VSV), herpes simplex virus 1 (HSV-1), Zika virus (ZIKV), or especially SARS-CoV-2 resulted in a reduction in endogenous levels of NSUN2. Together, our findings reveal that NSUN2 serves as a negative regulator of interferon response by accelerating the fast turnover of IRF3 mRNA, while endogenous NSUN2 levels decrease after viral infection to boost antiviral responses for the effective elimination of viruses. Our results suggest a paradigm of innate antiviral immune responses ingeniously involving NSUN2-mediated m 5 C modification.

18.
World J Pediatr ; 17(6): 590-596, 2021 12.
Article in English | MEDLINE | ID: covidwho-1491418

ABSTRACT

BACKGROUND: A series of public health preventive measures has been widely implemented in Beijing to control the coronavirus disease-19 (COVID-19) pandemic since January 2020. An evaluation of the effects of these preventive measures on the spread of other respiratory viruses is necessary. METHODS: Respiratory specimens collected from children with acute respiratory infections were tested by NxTAG™ respiratory pathogen panel assays during January 2017 and December 2020. Specimens characterized as rhinoviruses (RVs) were sequenced to identify the RV species and types. Then, the epidemiology results of respiratory pathogens in 2020 were compared with those from 2017 to 2019 using SPSS statistics 22.0. RESULTS: The positive rates of adenovirus (ADV), influenza virus (flu), RVs, and respiratory syncytial virus (RSV) dropped abruptly by 86.31%, 94.67%, 94.59%, and 92.17%, respectively, from February to May 2020, compared with the average level in the same period during 2017-2019. Positive rates of RVs then steeply increased from June 2020 (13.77%), to an apex (37.25%) in August 2020, significantly higher than the average rates (22.51%) in August 2017-2019 (P = 0.005). The increase, especially in group ≥ 3 years, was accompanied by the reopening of schools and kindergartens after the 23rd and 24th week of 2020 in Beijing. CONCLUSIONS: Whereas the abrupt drop in viral pathogen positive rates from February to May 2020 revealed the remarkable effects of the COVID-19 preventive measures, the sharp increase in positive rates of RVs from the 23rd week of 2020 might be explained by the reopening of schools and kindergartens in Beijing.


Subject(s)
COVID-19 , Respiratory Tract Infections , Beijing/epidemiology , Child , China/epidemiology , Hospitals , Humans , Infant , Pandemics , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/prevention & control , Rhinovirus , SARS-CoV-2
19.
Nucleic Acids Res ; 50(D1): D817-D827, 2022 01 07.
Article in English | MEDLINE | ID: covidwho-1493884

ABSTRACT

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.


Subject(s)
Databases, Factual , Host Microbial Interactions , Virus Diseases , Animals , Chromatin Immunoprecipitation Sequencing , Gene Ontology , Genome, Viral , High-Throughput Nucleotide Sequencing , Host Microbial Interactions/genetics , Humans , Metadata , Sequence Analysis, RNA , Software , Transcriptome , User-Computer Interface , Virus Diseases/genetics , Virus Diseases/metabolism , Web Browser
20.
BMJ ; 369: m2195, 2020 06 10.
Article in English | MEDLINE | ID: covidwho-1430181

ABSTRACT

OBJECTIVE: To examine the protective effects of appropriate personal protective equipment for frontline healthcare professionals who provided care for patients with coronavirus disease 2019 (covid-19). DESIGN: Cross sectional study. SETTING: Four hospitals in Wuhan, China. PARTICIPANTS: 420 healthcare professionals (116 doctors and 304 nurses) who were deployed to Wuhan by two affiliated hospitals of Sun Yat-sen University and Nanfang Hospital of Southern Medical University for 6-8 weeks from 24 January to 7 April 2020. These study participants were provided with appropriate personal protective equipment to deliver healthcare to patients admitted to hospital with covid-19 and were involved in aerosol generating procedures. 77 healthcare professionals with no exposure history to covid-19 and 80 patients who had recovered from covid-19 were recruited to verify the accuracy of antibody testing. MAIN OUTCOME MEASURES: Covid-19 related symptoms (fever, cough, and dyspnoea) and evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, defined as a positive test for virus specific nucleic acids in nasopharyngeal swabs, or a positive test for IgM or IgG antibodies in the serum samples. RESULTS: The average age of study participants was 35.8 years and 68.1% (286/420) were women. These study participants worked 4-6 hour shifts for an average of 5.4 days a week; they worked an average of 16.2 hours each week in intensive care units. All 420 study participants had direct contact with patients with covid-19 and performed at least one aerosol generating procedure. During the deployment period in Wuhan, none of the study participants reported covid-19 related symptoms. When the participants returned home, they all tested negative for SARS-CoV-2 specific nucleic acids and IgM or IgG antibodies (95% confidence interval 0.0 to 0.7%). CONCLUSION: Before a safe and effective vaccine becomes available, healthcare professionals remain susceptible to covid-19. Despite being at high risk of exposure, study participants were appropriately protected and did not contract infection or develop protective immunity against SARS-CoV-2. Healthcare systems must give priority to the procurement and distribution of personal protective equipment, and provide adequate training to healthcare professionals in its use.


Subject(s)
Coronavirus Infections/prevention & control , Health Personnel , Infection Control/instrumentation , Pandemics/prevention & control , Personal Protective Equipment/supply & distribution , Pneumonia, Viral/prevention & control , Adult , Betacoronavirus , COVID-19 , China , Coronavirus Infections/diagnosis , Cross-Sectional Studies , Female , Humans , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Intensive Care Units , Male , Middle Aged , Occupational Exposure/prevention & control , Pneumonia, Viral/diagnosis , SARS-CoV-2
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