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1.
Vaccines ; 10(5):706, 2022.
Article in English | MDPI | ID: covidwho-1820443

ABSTRACT

The administration of COVID-19 vaccines has become increasingly essential to curb the pandemic. However, adverse events of acute kidney injury (AKI) emerge rapidly as the COVID-19 vaccination promotes. To investigate the intervenable risk factors of AKI, we searched the Vaccine Adverse Event Reporting System database and recorded adverse effects after COVID-19 vaccines from Dec 2020 to Jun 2021. We included 1149 AKI cases, of which 627 (54.6%) cases were reported following the Pfizer-BNT COVID-19 vaccine, and 433 (37.7%) were reported after the Moderna vaccine. A univariate analysis revealed that coexisting active illnesses (infections, uncontrolled hypertension, heart failure, etc.) have an unfavorable prognosis, with an increased risk of death (OR 2.35, 95% CI 1.70–3.25, p < 0.001). The other risk factors included older age and past disease histories. An adjusted regression analysis proved that coexisting active illnesses worsen AKI prognosis after COVID-19 vaccination, with a higher mortality risk (OR 2.19, 95% CI 1.48–3.25, p < 0.001). In subgroup analysis, we stratified different variables, and none revealed a significant effect modification on the association between coexisting active illnesses and AKI-associated death after vaccination (p-interaction >0.05). We found that coexisting active illnesses could complicate AKI after vaccines, but the potential causal relationship needed further investigation.

2.
Future Med Chem ; 2022 Apr 07.
Article in English | MEDLINE | ID: covidwho-1780171

ABSTRACT

Background: In the last two decades, the world has witnessed the emergence of zoonotic corona viruses (CoVs), which cause mild to severe respiratory diseases in humans. Human coronaviruses (HCoVs), mainly from the alpha-CoV and beta-CoV genera, have evolved to be highly pathogenic, such as SARS-CoV-2 causing the COVID-19 pandemic. These coronaviruses carry functional enzymes necessary for the virus life cycle, which represent attractive antiviral targets. Methods & Results: We aimed to therapeutically target the main protease (Mpro) of HCoV-NL63 and HCoV-229E (from alpha-CoV genus) and HCoV-OC43 and SARS-CoV-2 (from beta-CoV genus). Through virtual screening, we identified an FDA-approved drug dyphylline, a xanthine derivate, that binds to the catalytic dyad residues; histidine and cystine of the Mpro structures. Importantly, dyphylline dose-dependently inhibited the viral replication in cell culture models infected with the viruses. Conclusion: Our findings support the repurposing of dyphylline as a pan-coronavirus antiviral agent.

3.
Arch Virol ; 167(4): 1125-1130, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1694546

ABSTRACT

Given the structural similarities of the viral enzymes of different coronaviruses (CoVs), we investigated the potency of the anti-SARS-CoV-2 agents boceprevir and GC376 for counteracting seasonal coronavirus infections. In contrast to previous findings that both boceprevir and GC376 are potent inhibitors of the main protease (Mpro) of SARS-CoV-2, we found that GC376 is much more effective than boceprevir in inhibiting SARS-CoV-2 and three seasonal CoVs (NL63, 229E, and OC43) in cell culture models. However, these results are discordant with a molecular docking analysis that suggested comparable affinity of boceprevir and GC376 for the different Mpro enzymes of the four CoVs. Collectively, our results support future development of GC376 but not boceprevir (although it is an FDA-approved antiviral medication) as a pan-coronavirus antiviral agent. Furthermore, we caution against overinterpretation of in silico data when developing antiviral therapies.


Subject(s)
Antiviral Agents , COVID-19 , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , COVID-19/drug therapy , Humans , Molecular Docking Simulation , Proline/analogs & derivatives , Protease Inhibitors/pharmacology , Pyrrolidines , SARS-CoV-2 , Sulfonic Acids
5.
Sci Rep ; 11(1): 23465, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1556248

ABSTRACT

Human coronavirus NL63 (HCoV-NL63) mainly affects young children and immunocompromised patients, causing morbidity and mortality in a subset of patients. Since no specific treatment is available, this study aims to explore the anti-SARS-CoV-2 agents including favipiravir and remdesivir for treating HCoV-NL63 infection. We first successfully modelled the 3D structure of HCoV-NL63 RNA-dependent RNA polymerase (RdRp) based on the experimentally solved SARS-CoV-2 RdRp structure. Molecular docking indicated that favipiravir has similar binding affinities to SARS-CoV-2 and HCoV-NL63 RdRp with LibDock scores of 75 and 74, respectively. The LibDock scores of remdesivir to SARS-CoV-2 and HCoV-NL63 were 135 and 151, suggesting that remdesivir may have a higher affinity to HCoV-NL63 compared to SARS-CoV-2 RdRp. In cell culture models infected with HCoV-NL63, both favipiravir and remdesivir significantly inhibited viral replication and production of infectious viruses. Overall, remdesivir compared to favipiravir is more potent in inhibiting HCoV-NL63 in cell culture. Importantly, there is no evidence of resistance development upon long-term exposure to remdesivir. Furthermore, combining favipiravir or remdesivir with the clinically used antiviral cytokine interferon-alpha resulted in synergistic effects. These findings provided a proof-of-concept that anti-SARS-CoV-2 drugs, in particular remdesivir, have the potential to be repurposed for treating HCoV-NL63 infection.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Amides/chemistry , Antiviral Agents/chemistry , Coronavirus NL63, Human/enzymology , Pyrazines/chemistry , RNA-Dependent RNA Polymerase/chemistry , Adenosine Monophosphate/chemistry , Adenosine Monophosphate/metabolism , Adenosine Monophosphate/pharmacology , Alanine/chemistry , Alanine/metabolism , Alanine/pharmacology , Amides/metabolism , Amides/pharmacology , Animals , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Binding Sites , Cell Culture Techniques , Cell Line , Coronavirus NL63, Human/physiology , Haplorhini , Humans , Molecular Docking Simulation , Pyrazines/metabolism , Pyrazines/pharmacology , RNA-Dependent RNA Polymerase/metabolism , Virus Replication/drug effects
6.
Virology ; 564: 33-38, 2021 12.
Article in English | MEDLINE | ID: covidwho-1447220

ABSTRACT

Endemic seasonal coronaviruses cause morbidity and mortality in a subset of patients, but no specific treatment is available. Molnupiravir is a promising pipeline antiviral drug for treating SARS-CoV-2 infection potentially by targeting RNA-dependent RNA polymerase (RdRp). This study aims to evaluate the potential of repurposing molnupiravir for treating seasonal human coronavirus (HCoV) infections. Molecular docking revealed that the active form of molnupiravir, ß-D-N4-hydroxycytidine (NHC), has similar binding affinity to RdRp of SARS-CoV-2 and seasonal HCoV-NL63, HCoV-OC43 and HCoV-229E. In cell culture models, treatment of molnupiravir effectively inhibited viral replication and production of infectious viruses of the three seasonal coronaviruses. A time-of-drug-addition experiment indicates the specificity of molnupiravir in inhibiting viral components. Furthermore, combining molnupiravir with the protease inhibitor GC376 resulted in enhanced antiviral activity. Our findings highlight that the great potential of repurposing molnupiravir for treating seasonal coronavirus infected patients.


Subject(s)
Coronavirus 229E, Human/genetics , Coronavirus Infections/drug therapy , Coronavirus NL63, Human/genetics , Coronavirus OC43, Human/genetics , Cytidine/analogs & derivatives , Hydroxylamines/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Common Cold/drug therapy , Coronavirus 229E, Human/drug effects , Coronavirus 229E, Human/physiology , Coronavirus NL63, Human/drug effects , Coronavirus NL63, Human/physiology , Coronavirus OC43, Human/drug effects , Coronavirus OC43, Human/physiology , Cytidine/pharmacology , Humans , Molecular Docking Simulation , Protein Binding/drug effects , Pyrrolidines/pharmacology , RNA-Dependent RNA Polymerase/chemistry , RNA-Dependent RNA Polymerase/genetics , RNA-Dependent RNA Polymerase/metabolism , Seasons , Sulfonic Acids/pharmacology , Virus Replication/drug effects , Virus Replication/genetics
7.
Int J Psychol ; 56(4): 512-521, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1141315

ABSTRACT

Using data collected from two provinces in China through an online survey, the current study aimed to investigate left-behind children's emotional and academic adjustment during the COVID-19 pandemic in China. The participants included 1780 left-behind (960 boys) and 1500 non-left-behind (811 boys) children in elementary and junior high school with a mean age of 11.23. Self-reported questionnaires concerning children's depression, loneliness, anxiety, and academic adjustment, and parents' coping with children's negative emotions were completed. The results suggested that compared with non-left-behind children, left-behind children's depression and anxiety symptoms were more severe and their academic adjustment was poorer. However, left-behind children had lower levels of loneliness than non-left-behind children. Additionally, supportive coping types, especially emotion-focused and problem-focused reactions, were significantly negatively correlated with children's depression and anxiety. Unsupportive coping types, especially distress and punitive reactions, were significantly positively correlated with children's depression and anxiety symptoms. Moreover, the relationships between punitive reactions and depression, ignoring and loneliness and problem-focused reactions and academic adjustment were significantly stronger in left-behind children. Hence, during the pandemic, left-behind children were still at a disadvantage even with their parents' company. However, parents' coping style towards left-behind children's negative emotions played a significant role in their adjustment.


Subject(s)
Adaptation, Psychological/physiology , COVID-19/psychology , Emotions/physiology , Parent-Child Relations , Parents/psychology , Social Adjustment , Anxiety/epidemiology , Anxiety/psychology , COVID-19/epidemiology , Child , Child, Preschool , China/epidemiology , Female , Humans , Loneliness/psychology , Male , Pandemics , Surveys and Questionnaires
8.
Int J Infect Dis ; 102: 375-380, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1060138

ABSTRACT

OBJECTIVES: This study aimed to comprehensively compare the clinical features of hospitalized COVID-19 patients with hospitalized 2009 influenza pandemic patients. METHODS: Medline, Embase, Web of Science, Cochrane CENTRAL, and Google scholar were systematically searched to identify studies related to COVID-19 and the 2009 influenza pandemic. The pooled incidence rates of clinical features were estimated using the DerSimonian-Laird random-effects model with the Freeman-Tukey double arcsine transformation method. RESULTS: The incidence rates of fever, cough, shortness of breath, sore throat, rhinorrhea, myalgia/muscle pain, or vomiting were found to be significantly higher in influenza patients when compared with COVID-19 patients. The incidence rates of comorbidities, including cardiovascular disease/hypertension and diabetes, were significantly higher in COVID-19 compared with influenza patients. In contrast, comorbidities such as asthma, chronic obstructive pulmonary disease, and immunocompromised conditions were significantly more common in influenza compared with COVID-19 patients. Unexpectedly, the estimated rates of intensive care unit admission, treatment with extracorporeal membrane oxygenation, treatment with antibiotics, and fatality were comparable between hospitalized COVID-19 and 2009 influenza pandemic patients. CONCLUSIONS: This study comprehensively estimated the differences and similarities of the clinical features and burdens of hospitalized COVID-19 and 2009 influenza pandemic patients. This information will be important to better understand the current COVID-19 pandemic.


Subject(s)
COVID-19/therapy , Influenza, Human/therapy , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Child , Child, Preschool , Female , Hospitalization , Humans , Infant , Influenza, Human/diagnosis , Influenza, Human/epidemiology , Influenza, Human/virology , Male , Middle Aged , Orthomyxoviridae/physiology , Pandemics , SARS-CoV-2/physiology , Young Adult
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