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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-336200

ABSTRACT

Background: The emergence of the SARS-CoV-2 Omicron variant has been triggering the new wave of COVID-19 globally. However, the risk factors and outcomes for radiological abnormalities in the early convalescent stage (1 month after onset) of Omicron infected patients are still unknown. Methods: : Patients were retrospectively enrolled if they were admitted to the hospital due to COVID-19 and underwent chest CT scans during hospitalization between 8 January and 24 February 2022. The chest CTs and clinical data obtained at admission and 1 month after onset were longitudinally analyzed. Spearman rank correlation analysis was used to investigate the correlation between laboratory markers and CT scores. Uni-/multi-variable logistic regression tests were performed to explore independent risk factors for radiological abnormalities at admission and residual pulmonary abnormalities after 1 month. Results: : We assessed 316 COVID-19 patients, including 47% with radiological abnormalities at admission and 23% with residual pulmonary abnormalities at 1-month follow-up. In a multivariate regression analysis, age ≥ 50 years, body mass index ≥ 23.87, days after vaccination ≥ 81 days, lymphocyte count ≤ 1.21×10 -9 /L, Interleukin-6 ≥ 10.05 pg/mL and IgG ≤ 14.140 S/CO were independent risk factors for CT abnormalities at admission (odds ratio = 2.870, 4.171, 2.360, 2.826, 3.886 and 2.828, respectively;P < 0.05 for each comparison). The presence of interlobular septal thickening and IL-6 ≥ 5.85 pg/mL were the independent risk factors for residual pulmonary abnormalities at 1-month follow-up (odds ratio = 3.619 and 3.197, respectively;P < 0.05 for each comparison). There were no significant changes in the number of involved lung lobes ( P = 0.308) and total CT score ( P = 0.068) during the early convalescent stage. And the level of IL-6 showed positive correlation with CT score at admission (spearman r = 0.202, P = 0.030). Conclusions: : The higher IL-6 level was a common independent risk factor for CT abnormalities at admission and residual pulmonary abnormalities at 1-month follow-up. And there were no obvious radiographic changes during the early convalescent stage in patients with residual pulmonary abnormalities.

2.
Journal of International Students ; 11:1-18, 2021.
Article in English | ProQuest Central | ID: covidwho-1717622

ABSTRACT

Due to uneven and hierarchical global context, the United States has been the world's number one "Educational Hub" (Knight, 2011), leading the internationalization of higher education in multiple forms, the top priority of which lies in international student recruitment and enrollment. However, the COVID-19 pandemic has thoroughly disrupted the traditional mobility experience-a situation that has broader implications for the demographic landscape of US higher education. This article explores how COVID-19 and pandemic-related Sinophobia affect Chinese students' perspectives on their educational decision-making. Based on Zoom interviews of a sample of 21 Chinese undergraduate students, this study demonstrates that despite the leading role of the US in international education, it is gradually losing appeal to Chinese students due to disillusionment with the romanticized imaginary of the US, anxiety about uncertain policies, and safety concerns. The unidirectional student mobility from mainland China to the US may be interrupted with Singapore and Hong Kong as the emerging destinations.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325346

ABSTRACT

Objective: The purpose of this study was to determine the prevalence and differences in etiology, clinical manifestations, and psychological activity of coronavirus disease-19 (COVID-19) among patients. Results We recruited 90 subjects, 30 were healthy controls, 30 were patients with moderate infection, and 30 were patients with severe/critical infections. No significant differences were noted in the sex ratio, mean age, body mass index, or blood type;however, the history of exposure of the patients with COVID-19 compared with healthy controls was noteworthy. The erythrocyte sedimentation rate, as well as the levels of C-reactive protein and serum amyloid A (SAA) were all increased. In terms of mental health, there were significant differences in the worry scores between severely and moderately infected patients and healthy controls. There was a significant difference in depression scores between patients with moderate infection and healthy hypertension, and there was also a significant difference in dream worry scores. Analysis of the Mini-Mental State Examination scores showed that for patients with moderate infection, the depression score was moderately and positively correlated with the dream anxiety score. For patients with severe infection, the anxiety score was positively correlated with the dream anxiety score, and the depression score was moderately and positively correlated with the dream anxiety score. Conclusion Patients with severe infection showed increased pain and sputum in the pharyngeal area compared with patients with moderate infection. Patients with blood type A may be more susceptible to COVID-19, and lymphopenia may indicate worsening of COVID-19.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325171

ABSTRACT

The diagnosis and disease course monitoring of COVID-19 are mainly based on RT-PCR analysis of RNAs extracted from pharyngeal or nasopharyngeal swabs with potential live virus, posing a high risk to medical practitioners. Here, we investigated the feasibility of applying serum proteomics to classify COVID-19 patients in the nucleic acid positive (NCP) and negative (NCN) stages. We analyzed the proteome of 320 inactivated serum samples from 144 COVID-19 patients, and 45 controls and shortlisted 42 regulated proteins in the severe group and 12 regulated proteins in the non-severe group. Together with several key clinical indexes including days after symptom onset, platelet counts and magnesium, we developed machine learning models to classify NCP and NCN with an AUC of 0.94 for the severe cases and 0.89 for the non-severe cases. This study suggests the feasibility of utilizing quantitative serum proteomics for NCP-NCN classification.Funding: This work was supported by grants from the National Key R&D Program of China(No. 2020YFE0202200), National Natural Science Foundation of China (81672086), Zhejiang Province Analysis Test Project (2018C37032), the National Natural Science Foundation of China (81972492, 21904107), Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholars (LR19C050001), Zhejiang Medical and Health Science and Technology Plan (2021KY394), Hangzhou Agriculture andSociety Advancement Program (20190101A04), and Westlake Education Foundation, Tencent Foundation.Conflict of Interest: Tiannan Guo is shareholder of Westlake Omics Inc. W.G. and N.X. are employees of Westlake Omics Inc. The remaining authors declare no competing interests.Ethical Approval: This study has been approved by both the Ethical/Institutional Review Boards of Taizhou Hospital and Westlake University. Informed contents from patients were waived by the boards.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324776

ABSTRACT

Background: Bacterial co-infection in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a critical factor that increases the complexity and treatment of coronavirus disease 2019 (COVID-19). Methods: We collected the clinical laboratory data of 1799 patients with confirmed COVID-19 who were admitted to Jinyintan Hospital in Wuhan, China, between January 1 to April 26, 2020. The bacterial co-infection along with disease progression was analyzed. Other inflammatory markers, including C-reactive protein (CRP), white blood cells (WBC), lymphocytes (L), neutrocytes (N), interleukin-6 (IL-6), and procalcitonin (PCT), were assessed to estimate the progression of COVID-19. Results: We found that 191 of the 1799 (10.62%) patients had bacterial co-infection. The most prevalent causative agents for bacterial co-infection were Klebsiella pneumoniae (91 cases, 5.06%) and Acinetobacter baumannii (66 cases, 3.67%). The most patients with bacterial co-infection showed extensive drug-resistance. The outcomes of patients with bacterial co-infection were worse than those of patients without bacterial co-infection. Conclusions: Secondary bacterial pneumonia during virus infection is a major risk factor for high mortality resulting from severe pneumonia caused by COVID-19.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-317899

ABSTRACT

COVID-19 pandemic lockdowns and mobility restrictions have forced many individuals to work from home, leading to diverse isolation-induced mental health consequences. Using the granularity of foot traffic data, we show that prolonged work from home during the COVID-19 outbreak dampens managerial sentiment. This baseline result is robust to the identification strategy exploiting the staggered implementation of stay-at-home orders across the United States. Further analyses indicate that the induced negative sentiment elevates managers' perceived risk, driving them to accumulate more cash in response to the unprecedented COVID-19 cash-flow shock. But this increase in cash destroys shareholder value.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-312749

ABSTRACT

Cancer patients are more susceptible to SARS-CoV-2 infection and generally have higher mortality rate. Anti-SARS-CoV-2 IgG is an important consideration for the patients in this COVID-19 pandemic. Recent researches suggested the rapid decay of anti-SARS-CoV-2 antibodies in the general population, but the decline rate of the antibodies in cancer patients was unknown. In this observational study, we reported the clinical features of the 53 cancer patients infected by SARS-CoV-2 from two hospitals in Wuhan, China and tracked the presence of anti-SARS-CoV-2 antibodies in the patients for more than 12 months. We found the duration (days) of anti-SARS-CoV-2 IgG in the patients was significant longer in chemotherapy (mean: 175;range: 75 to 315) and radiotherapy groups (mean: 168;range: 85 to 265) than in non-chemo- or radio-therapy group (mean: 58;range:21 to 123) after their recovery from COVID-19. We also used single-cell RNA sequencing to track the immunologic changes in a representative patient infected by COVID-19 for more than one year, and found that CD8 + effective T cells, memory B cells and plasma cells were persistently activated in the patient undergoing chemotherapy. Together, our findings show that chemotherapy and radiotherapy might be beneficial to extend the duration of anti-SARS-CoV-2 IgG.

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-310725

ABSTRACT

Background: In December 2019, COVID-19 emerged in Wuhan, China. By 8 July 2020, the cumulative number of infected people worldwide had exceeded 11.50 million. It has been reported that a variety of indicators, including lymphocytes, can predict the progression of COVID-19 disease, but the clinical application value of eosinophils has not received widespread attention. It’s specific changes in the course of the disease, as well as the relationship with severity and prognosis of COVID-19 patients, need to be further studied.Method: In this multicenter, retrospective study, we collected data on laboratory-confirmed 482 COVID-19 patients from three hospitals in Wuhan, China, who died or were discharged between February 1, 2020, and February 20, 2020. By collecting the clinical data and laboratory examination results of the patients, we analyzed the changes of eosinophil and lymphocyte count in patients with different severity and outcomes, so as to study their relationship with the severity and prognosis, to compare the diagnostic effects of lymphocytes and eosinophils on severe COVID-2019 patients.Result: A total of 482 patients were enrolled in this study. Of those, 39.0% were severe patients and 13.3% were nonsurvivors. All the nonsurvivors were from the severe group. The count of eosinophil remained relatively lower levels during hospitalization in the severe and nonsurvival groups compared with the nonsevere and survival groups (all P < 0.05). Patients with the lowest eosinophil count during hospitalization reduced to <0.02×10⁹/L and =0.00×10⁹/L had higher rates of severity and fatality (all P < 0.05). The lowest counts of lymphocyte and eosinophil during hospitalization were used to analyze the diagnostic efficacy of severe COVID-19, and their diagnostic effects were similar. The cutoff values were ≤0.72×10⁹/L and =0.00×10⁹/L, and the areas under the curve were 0.768 and 0.740, respectively. Multivariate Cox regression model showed that the older age, the emergence of dyspnea, the increase of the white blood cell count on admission, the decrease of lymphocyte count on admission, and eosinophil count reduced to =0.00×10⁹/L on admission were associated with fatal outcome.Conclusion: Eosinophil and lymphocyte count remained relatively lower levels during hospitalization in the severe and nonsurvival COVID-19 patients, and patients with eosinophil decline had higher rates of severity and fatality. Eosinophils = 0.00×10⁹/L and lymphocytes ≤0.72×10⁹/L had the similar efficacy to diagnosis the severe COVID-19 patients. Compared with lymphocytes, eosinophils could also be used to diagnose severe COVID-19 patients and predict prognosis.Funding Statement: This study is funded by grants from the Natural Science Foundation of China (81974383 and 81772607 to W.Y.;81770554 and 81570501 to Y.F.)Declaration of Interests: None.Ethics Approval Statement: The study was approved by the Ethics Commission of Wuhan Tongji Hospital, Union Hospital, and Jin Yin-tan Hospital, and written informed consent was waived.

9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-305437

ABSTRACT

In response to the recent elevated corporate credit risk environment in China’s credit market, we develop a probability of default (PD) measure for Chinese companies using actual corporate bond defaults by applying the Least Absolute Shrinkage and Selection Operator (LASSO) machine learning model. Our PD measure is applicable to publicly listed and also, importantly, to unlisted companies. Our measure’s bond default prediction accuracy outperforms models generated by alternative machine learning techniques and other prominent credit risk measures. Further analysis documents a large pricing effect of corporate default risk using our PD measure in primary and secondary bond markets. The pricing effect of default risk became more pronounced following two crucial market events in 2014 that raised market awareness of credit risk and is stronger for bonds likely traded by retail and foreign investors. In the cross section of bond and stock returns, we observe a positive distress risk premium after controlling for common risk factors. Finally, stocks of low PD firms outperformed those of high PD firms during the COVID-19 pandemic.

10.
Journal of Multivariate Analysis ; : 104956, 2022.
Article in English | ScienceDirect | ID: covidwho-1665206

ABSTRACT

In the process of modeling longitudinal data, we focus on the case that the studied population is comprised of different groups of individuals and individuals within the same group share the similar kind of mean progression trajectories, where finite mixture models (FMM) are often used to address this kind of unobserved heterogeneity in terms of mean. Existing methods, such as parametric and semiparametric mixture regression, usually model the mean in each subpopulation with assumption that observations sharing a common trajectory are independent or their covariance structure is pre-specified, but less research considers modeling of covariance structures while accounting for heterogeneity. In this paper, we introduce a joint model which models the mean and covariance structures simultaneously in a finite normal mixture regression, demonstrating how important the within-subject correlation is in clustering longitudinal data. Model parameters are estimated with an iteratively re-weighted least squares EM algorithm (IRLS-EM). Our estimators are shown to be consistent and asymptotically normal. We can identify different mean trajectories and covariance structures in all clusters. Simulations show that the proposed method performs well and gives more accurate clustering results by introducing covariance modeling. Real data analysis is also used to illustrate the usefulness of the proposed method, and it presents good performance in clustering COVID-19 deaths for European countries in terms of progression trajectory.

11.
Hypertens Res ; 45(5): 856-865, 2022 05.
Article in English | MEDLINE | ID: covidwho-1641956

ABSTRACT

The global coronavirus disease 2019 (COVID-19) pandemic has led to a health crisis. It remains unclear how anxiety affects blood pressure (BP) and cardiovascular risk among older patients with hypertension. In this study, we extracted longitudinal data on home BP monitored via a smartphone-based application in 3724 elderly patients with hypertension from a clinical trial (60-80 years; 240 in Wuhan and 3484 in non-Wuhan areas) to examine changes in morning BP during the COVID-19 outbreak in China. Anxiety was evaluated using Generalized Anxiety Disorder-7 item scores. Changes in morning systolic BP (SBP) were analyzed for five 30-day periods during the pandemic (October 21, 2019 to March 21, 2020), including the pre-epidemic, incubation, developing, outbreak, and plateau periods. Data on cardiovascular events were prospectively collected for one year. A total of 262 individuals (7.0%) reported an increased level of anxiety, and 3462 individuals (93.0%) did not. Patients with anxiety showed higher morning SBP than patients without anxiety, and the between-group differences in SBP change were +1.2 mmHg and +1.7 mmHg during the outbreak and plateau periods (P < 0.05), respectively. The seasonal BP variation in winter among patients with anxiety was suppressed during the pandemic. Anxious patients had higher rates of uncontrolled BP. During the 1-year follow-up period, patients with anxiety had an increased risk of cardiovascular events with a hazard ratio of 2.47 (95% confidence interval, 1.10-5.58; P = 0.03). In summary, COVID-19-related anxiety was associated with a short-term increase in morning SBP among older patients and led to a greater risk of cardiovascular events. (ClinicalTrials. gov number, NCT03015311).


Subject(s)
COVID-19 , Hypertension , Aged , Aged, 80 and over , Anxiety/epidemiology , Anxiety Disorders/epidemiology , Blood Pressure/physiology , Blood Pressure Monitoring, Ambulatory , Humans , Hypertension/complications , Hypertension/epidemiology , Middle Aged , Pandemics
12.
J Proteome Res ; 21(1): 90-100, 2022 01 07.
Article in English | MEDLINE | ID: covidwho-1531980

ABSTRACT

RT-PCR is the primary method to diagnose COVID-19 and is also used to monitor the disease course. This approach, however, suffers from false negatives due to RNA instability and poses a high risk to medical practitioners. Here, we investigated the potential of using serum proteomics to predict viral nucleic acid positivity during COVID-19. We analyzed the proteome of 275 inactivated serum samples from 54 out of 144 COVID-19 patients and shortlisted 42 regulated proteins in the severe group and 12 in the non-severe group. Using these regulated proteins and several key clinical indexes, including days after symptoms onset, platelet counts, and magnesium, we developed two machine learning models to predict nucleic acid positivity, with an AUC of 0.94 in severe cases and 0.89 in non-severe cases, respectively. Our data suggest the potential of using a serum protein-based machine learning model to monitor COVID-19 progression, thus complementing swab RT-PCR tests. More efforts are required to promote this approach into clinical practice since mass spectrometry-based protein measurement is not currently widely accessible in clinic.


Subject(s)
COVID-19 , Humans , Proteomics , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Specimen Handling
13.
Int J Biol Sci ; 17(4): 1079-1087, 2021.
Article in English | MEDLINE | ID: covidwho-1524445

ABSTRACT

Fibrinogen-associated protein (FREP) family is a family of proteins with a fibrin domain at the carboxyl terminus. Recent investigations illustrated that two members of FREP family, fibrinogen-like protein-1 (FGL1) and fibrinogen-like protein-2 (FGL2), play crucial roles in cancer by regulating the proliferation, invasion, and migration of tumor cells, or regulating the functions of immune cells in tumor microenvironment. Meanwhile, they are potential targets for medical intervention of tumor development. In this review, we discussed the structure, and the roles of FGL1 and FGL2 in tumors, especially the roles in regulating immune cell functions.


Subject(s)
Fibrinogen/metabolism , Neoplasms/metabolism , Tumor Microenvironment/immunology , Animals , Humans , Immunotherapy , Molecular Targeted Therapy , Neoplasms/immunology , Neoplasms/therapy , Signal Transduction
14.
Vaccines (Basel) ; 9(9)2021 Sep 04.
Article in English | MEDLINE | ID: covidwho-1390815

ABSTRACT

This systematic review and meta-analysis was conducted to compare the safety and efficacy of 2019 novel coronavirus disease (COVID-19) vaccines according to vaccine platform and severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection severity. Articles published between 24 January 2020 and 30 May 2021 were retrieved via a PubMed and EMBASE search. A total of 12 reports on phase-3 clinical trials and observational studies of COVID-19 vaccines were included in the review. In terms of vaccine safety, mRNA vaccines showed more relevance to serious adverse events than viral vector and inactivated vaccines, but no solid evidence indicated that COVID-19 vaccines directly caused serious adverse events. Serious metabolic, musculoskeletal, immune-system, and renal disorders were more common among inactivated vaccine recipients, and serious gastrointestinal complications and infections were more common among viral vector and inactivated vaccine recipients. The occurrence of serious vessel disorders was more frequent in mRNA vaccines. In terms of efficacy, two mRNA vaccine doses conferred a lesser risk of SARS-COV-2 infection (odds ratio: 0.05; 95% confidence interval: 0.02-0.13) than did vaccination with viral vector and inactivated vaccines. All vaccines protected more against symptomatic than asymptomatic cases (risk ratio, 0.11 vs. 0.34), but reduced the risk of severe SARS-COV-2 infection. The COVID-19 vaccines assessed in this study are sufficiently safe and effective. The results indicate that two mRNA vaccine doses prevent SARS-COV-2 infection most effectively, but further research is needed due to the high degree of heterogeneity among studies in this sample. Interventions should be implemented continuously to reduce the risks of infection after one vaccine dose and asymptomatic infection.

17.
Sci Rep ; 11(1): 17381, 2021 08 30.
Article in English | MEDLINE | ID: covidwho-1379332

ABSTRACT

Cancer patients are more susceptible to SARS-CoV-2 infection and generally have higher mortality rate. Anti-SARS-CoV-2 IgG is an important consideration for the patients in this COVID-19 pandemic. Recent researches suggested the rapid decay of anti-SARS-CoV-2 antibodies in the general population, but the decline rate of the antibodies in cancer patients was unknown. In this observational study, we reported the clinical features of the 53 cancer patients infected by SARS-CoV-2 from Wuhan, China and tracked the presence of anti-SARS-CoV-2 antibodies in the patients for more than 12 months. We found the duration (days) of anti-SARS-CoV-2 IgG in the patients was significant longer in chemotherapy (mean: 175; range: 75 to 315) and radiotherapy groups (mean: 168; range: 85 to 265) than in non-chemo- or radio-therapy group (mean: 58; range: 21 to 123) after their recovery from COVID-19. We also used single-cell RNA sequencing to track the immunologic changes in a representative patient recovered  from COVID-19 and found that CD8 + effective T cells, memory B cells and plasma cells were persistently activated in the patient undergoing chemotherapy. Together, our findings show that chemotherapy and radiotherapy might be beneficial to extend the duration of anti-SARS-CoV-2 IgG.


Subject(s)
COVID-19/blood , Immunoglobulin G/analysis , Neoplasms/immunology , Neoplasms/virology , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Viral/analysis , B-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/metabolism , COVID-19/immunology , China , Drug Therapy , Female , Humans , Male , Middle Aged , Neoplasms/drug therapy , Neoplasms/radiotherapy , Plasma Cells/metabolism , Radiotherapy , SARS-CoV-2/genetics , Sequence Analysis, RNA , Single-Cell Analysis , Time Factors
18.
Journal of Modern Laboratory Medicine ; 35(6):132-134, 2020.
Article in Chinese | GIM | ID: covidwho-1264600

ABSTRACT

Objective: To study the stability of the novel coronavirus pneumonia (COVID-19) throat swab and the extracted nucleic acid after heat inactivation at 56 degrees Celsius for 30 min at 4 degrees Celsius.

20.
Protein Cell ; 12(11): 877-888, 2021 11.
Article in English | MEDLINE | ID: covidwho-1188202

ABSTRACT

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (Mpro), PLpro is responsible for processing the viral replicase polyprotein into functional units. Therefore, it is an attractive target for antiviral drug development. Here we discovered four compounds, YM155, cryptotanshinone, tanshinone I and GRL0617 that inhibit SARS-CoV-2 PLpro with IC50 values ranging from 1.39 to 5.63 µmol/L. These compounds also exhibit strong antiviral activities in cell-based assays. YM155, an anticancer drug candidate in clinical trials, has the most potent antiviral activity with an EC50 value of 170 nmol/L. In addition, we have determined the crystal structures of this enzyme and its complex with YM155, revealing a unique binding mode. YM155 simultaneously targets three "hot" spots on PLpro, including the substrate-binding pocket, the interferon stimulating gene product 15 (ISG15) binding site and zinc finger motif. Our results demonstrate the efficacy of this screening and repurposing strategy, which has led to the discovery of new drug leads with clinical potential for COVID-19 treatments.


Subject(s)
Coronavirus Papain-Like Proteases/chemistry , High-Throughput Screening Assays/methods , Protease Inhibitors/chemistry , Antiviral Agents/chemistry , Antiviral Agents/metabolism , Antiviral Agents/therapeutic use , Binding Sites , COVID-19/drug therapy , COVID-19/virology , Coronavirus Papain-Like Proteases/genetics , Coronavirus Papain-Like Proteases/metabolism , Crystallography, X-Ray , Drug Evaluation, Preclinical , Drug Repositioning , Humans , Imidazoles/chemistry , Imidazoles/metabolism , Imidazoles/therapeutic use , Inhibitory Concentration 50 , Molecular Dynamics Simulation , Mutagenesis, Site-Directed , Naphthoquinones/chemistry , Naphthoquinones/metabolism , Naphthoquinones/therapeutic use , Protease Inhibitors/metabolism , Protease Inhibitors/therapeutic use , Protein Structure, Tertiary , Recombinant Proteins/biosynthesis , Recombinant Proteins/chemistry , Recombinant Proteins/isolation & purification , SARS-CoV-2/isolation & purification
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