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1.
Biosensors & bioelectronics ; 2022.
Article in English | EuropePMC | ID: covidwho-1615442

ABSTRACT

The development of reliable, sensitive, and fast devices for the diagnosis of COVID-19 is of great importance in the pandemic of the new coronavirus. Here, we proposed a new principle of analysis based on a combination of reverse transcription and isothermal amplification of a fragment of the gene encoding the S protein of the SARS-CoV-2 and the CRISPR/Cas13a reaction for cleavage of the specific probe. As a result, the destroyed probe cannot be detected on an immunochromatographic strip using quantum fluorescent dots. Besides, the results can be obtained by an available and inexpensive portable device. By detecting SARS-CoV-2 negative (n = 25) and positive (n = 62) clinical samples including throat swabs, sputum and anal swabs, the assay showed good sensitivity and specificity of the method and could be completed within 1 h without complicated operation and expensive equipment. These superiorities showed its potential for fast point-of-care screening of SARS-CoV-2 during the outbreak, especially in remote and underdeveloped areas with limited equipment and resources.

2.
Ann Palliat Med ; 10(12): 12280-12290, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1579500

ABSTRACT

BACKGROUND: The objective of this study was to carry out a retrospective analysis of the progression of electrocardiographic (ECG) findings over time, based on biomarkers for myocardial injuries in patients with coronavirus disease 2019 (COVID-19). Also, the ECG observations were assessed for possible prognostic use. METHODS: Diagnostic criteria provided by the Coronavirus Pneumonia Diagnosis and Treatment Program of the Chinese National Health Commission were used. We conducted a retrospective analysis of 31 COVID-19 cases diagnosed as positive by high-throughput sequencing of nasopharyngeal nucleic acid test and admitted to Sichuan Province Public Health Clinical Medical Center, Sichuan Province, China. Based on changes in biomarkers, the 31 participants were divided into a non-myocardial injury group (A) and a myocardial injury group (B). Our study observed the dynamic changes and new abnormal changes of the ECG during the hospitalization of patients. RESULTS: The results summarized in the 4 following points: (I) the time sequence changes for ST and T indicated that the absolute ST-segment depression and T-wave inversion values in group B were larger. (II) The heart rate (HR) and RV5 values in group B were higher, the QTC value for group B was lower. (III) The sensitivity of ST-segment depression for the diagnosis of myocardial injury was 32.60% and the specificity was 90.50%. The sensitivity of T-wave inversion was 41.30% and the specificity was 85.10%. (IV) Lactate dehydrogenase (LDH) is a major factor affecting patient's death. CONCLUSIONS: If abnormal ST-T, increased heart rate, shortened QTC interval, and high ventricular voltage are observed in a COVID-19 patient, it may infer that myocardial damage has occurred. Using ECG as a point of reference for change can compensate for the time limitation of myocardial enzyme index. Regardless of the stage of disease development, ECG can reflect myocardial damage. Particularly in the 8-12 days after hospitalization, almost all myocardial enzymes cannot be applied. The ST-depression and T-wave inversion had diagnostic significance with relatively high sensitivity and specificity for myocardial injury. Assessment of LDH and biomarkers in combination with ECG can more accurately reflect myocardial injury, and facilitate prompt clinical diagnosis and treatment.


Subject(s)
COVID-19 , Electrocardiography , Humans , Prognosis , Retrospective Studies , SARS-CoV-2
3.
Eur J Med Chem ; 227: 113966, 2022 Jan 05.
Article in English | MEDLINE | ID: covidwho-1487705

ABSTRACT

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unprecedented in human history. As a major structural protein, nucleocapsid protein (NPro) is critical to the replication of SARS-CoV-2. In this work, 17 NPro-targeting phenanthridine derivatives were rationally designed and synthesized, based on the crystal structure of NPro. Most of these compounds can interact with SARS-CoV-2 NPro tightly and inhibit the replication of SARS-CoV-2 in vitro. Compounds 12 and 16 exhibited the most potent anti-viral activities with 50% effective concentration values of 3.69 and 2.18 µM, respectively. Furthermore, site-directed mutagenesis of NPro and Surface Plasmon Resonance (SPR) assays revealed that 12 and 16 target N-terminal domain (NTD) of NPro by binding to Tyr109. This work found two potent anti-SARS-CoV-2 bioactive compounds and also indicated that SARS-CoV-2 NPro-NTD can be a target for new anti-virus agents.


Subject(s)
Antiviral Agents/chemistry , Coronavirus Nucleocapsid Proteins/antagonists & inhibitors , Phenanthridines/chemistry , SARS-CoV-2/metabolism , Animals , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Binding Sites , COVID-19/drug therapy , COVID-19/virology , Cell Survival/drug effects , Chlorocebus aethiops , Coronavirus Nucleocapsid Proteins/metabolism , Drug Design , Humans , Kinetics , Molecular Docking Simulation , Phenanthridines/metabolism , Phenanthridines/pharmacology , Phenanthridines/therapeutic use , Phosphoproteins/antagonists & inhibitors , Phosphoproteins/metabolism , Protein Binding , Protein Structure, Tertiary , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Vero Cells
4.
Traditional Medicine Research ; 5(3):160-166, 2020.
Article in English | CAB Abstracts | ID: covidwho-1366019

ABSTRACT

Huajuhong (Exocarpium Citri grandis, ECG) is a traditional Chinese herbal medicine and has been used for the treatment of respiratory diseases for hundreds of years. Recently, ECG has been listed in a traditional Chinese medicine formula in the Guidelines for the Diagnosis and Treatment of Coronavirus Disease 2019 (sixth edition) in China. To date, the effect and mechanism of ECG against respiratory diseases have not been systematically reviewed. In this paper, the researchers summarized the effects of ECG and its pharmacologically active compound naringin in functioning as an antitussive and expectorant, improving lung function, alleviating acute lung injury, attenuating pulmonary fibrosis, and enhancing antiviral immune response, so as to provide a reference for its clinical application in the prevention and treatment of multiple respiratory diseases, including coronavirus disease 2019.

5.
Nat Commun ; 12(1): 5000, 2021 08 17.
Article in English | MEDLINE | ID: covidwho-1361637

ABSTRACT

The successive emergences and accelerating spread of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages and evolved resistance to some ongoing clinical therapeutics increase the risks associated with the coronavirus disease 2019 (COVID-19) pandemic. An urgent intervention for broadly effective therapies to limit the morbidity and mortality of COVID-19 and future transmission events from SARS-related coronaviruses (SARSr-CoVs) is needed. Here, we isolate and humanize an angiotensin-converting enzyme-2 (ACE2)-blocking monoclonal antibody (MAb), named h11B11, which exhibits potent inhibitory activity against SARS-CoV and circulating global SARS-CoV-2 lineages. When administered therapeutically or prophylactically in the hACE2 mouse model, h11B11 alleviates and prevents SARS-CoV-2 replication and virus-induced pathological syndromes. No significant changes in blood pressure and hematology chemistry toxicology were observed after injections of multiple high dosages of h11B11 in cynomolgus monkeys. Analysis of the structures of the h11B11/ACE2 and receptor-binding domain (RBD)/ACE2 complexes shows hindrance and epitope competition of the MAb and RBD for the receptor. Together, these results suggest h11B11 as a potential therapeutic countermeasure against SARS-CoV, SARS-CoV-2, and escape variants.


Subject(s)
Angiotensin-Converting Enzyme 2/drug effects , Angiotensin-Converting Enzyme 2/immunology , Antibodies, Neutralizing/administration & dosage , COVID-19/drug therapy , SARS-CoV-2/drug effects , Animals , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , COVID-19/immunology , COVID-19/mortality , COVID-19/virology , Chlorocebus aethiops , Disease Models, Animal , Epitopes , Female , HEK293 Cells , Haplorhini , Humans , Macaca fascicularis , Male , Mice , Mice, Inbred BALB C , Pandemics , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Vero Cells , Virus Activation
6.
Front Vet Sci ; 8: 687079, 2021.
Article in English | MEDLINE | ID: covidwho-1347366

ABSTRACT

Swine acute diarrhea syndrome (SADS) is a highly contagious infectious disease characterized by acute vomiting and watery diarrhea in neonatal piglets. The causative agent for SADS is the swine acute diarrhea syndrome coronavirus (SADS-CoV), an alphacoronavirus in the family Coronaviridae. Currently, SADS-CoV was identified only in Guangdong and Fujian provinces of China, not in any other regions or countries in the world. To explore the genetic diversity of SADS-CoV isolates, herein we comparatively analyzed 44 full-length genomes of viruses isolated in Guangdong and Fujian provinces during 2017-2019. The spike glycoprotein gene of SADS-CoV strain CH/FJWT/2018 isolated in Fujian province is distinct from that of other viral isolates in either spike glycoprotein gene-based phylogenetic analysis or whole genome-based gene similarity analysis. Moreover, at least 7 predicted linear B cell epitopes in the spike glycoprotein of CH/FJWT/2018 would be affected by amino acid variations when compared with a representative virus isolated in Guangdong province. The spike glycoprotein of coronaviruses determines viral host range and tissue tropism during virus infection via specific interactions with the cellular receptor and also plays critical roles in eliciting the production of neutralizing antibodies. Since SADS-CoVs have a broad cell tropism, the results in this report further emphasize that the spike glycoprotein gene is a pivotal target in the surveillance of SADS-CoV.

7.
Crit Care ; 25(1): 186, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1255959

ABSTRACT

BACKGROUND: In acute respiratory distress syndrome (ARDS), extravascular lung water index (EVLWi) and pulmonary vascular permeability index (PVPI) measured by transpulmonary thermodilution reflect the degree of lung injury. Whether EVLWi and PVPI are different between non-COVID-19 ARDS and the ARDS due to COVID-19 has never been reported. We aimed at comparing EVLWi, PVPI, respiratory mechanics and hemodynamics in patients with COVID-19 ARDS vs. ARDS of other origin. METHODS: Between March and October 2020, in an observational study conducted in intensive care units from three university hospitals, 60 patients with COVID-19-related ARDS monitored by transpulmonary thermodilution were compared to the 60 consecutive non-COVID-19 ARDS admitted immediately before the COVID-19 outbreak between December 2018 and February 2020. RESULTS: Driving pressure was similar between patients with COVID-19 and non-COVID-19 ARDS, at baseline as well as during the study period. Compared to patients without COVID-19, those with COVID-19 exhibited higher EVLWi, both at the baseline (17 (14-21) vs. 15 (11-19) mL/kg, respectively, p = 0.03) and at the time of its maximal value (24 (18-27) vs. 21 (15-24) mL/kg, respectively, p = 0.01). Similar results were observed for PVPI. In COVID-19 patients, the worst ratio between arterial oxygen partial pressure over oxygen inspired fraction was lower (81 (70-109) vs. 100 (80-124) mmHg, respectively, p = 0.02) and prone positioning and extracorporeal membrane oxygenation (ECMO) were more frequently used than in patients without COVID-19. COVID-19 patients had lower maximal lactate level and maximal norepinephrine dose than patients without COVID-19. Day-60 mortality was similar between groups (57% vs. 65%, respectively, p = 0.45). The maximal value of EVLWi and PVPI remained independently associated with outcome in the whole cohort. CONCLUSION: Compared to ARDS patients without COVID-19, patients with COVID-19 had similar lung mechanics, but higher EVLWi and PVPI values from the beginning of the disease. This was associated with worse oxygenation and with more requirement of prone positioning and ECMO. This is compatible with the specific lung inflammation and severe diffuse alveolar damage related to COVID-19. By contrast, patients with COVID-19 had fewer hemodynamic derangement. Eventually, mortality was similar between groups. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: ClinicalTrials.gov (NCT04337983). Registered 30 March 2020-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04337983 .


Subject(s)
COVID-19/metabolism , Capillary Permeability , Extravascular Lung Water/metabolism , Respiratory Distress Syndrome/metabolism , Severity of Illness Index , COVID-19/complications , Hemodynamics , Humans , Lung/blood supply , Male , Middle Aged , Monitoring, Physiologic/methods , Prognosis , Pulmonary Edema/metabolism , Thermodilution
8.
Echocardiography ; 38(8): 1245-1253, 2021 08.
Article in English | MEDLINE | ID: covidwho-1247170

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the clinical significance of remote consultation over bedside transthoracic echocardiography (RC-B-TTE) for patients with coronavirus disease 2019 (COVID-19). METHODS: Five frontline echocardiographers performed and interpreted B-TTE for 30 patients with COVID-19 in the isolation wards, and the on-site B-TTE reports (OSR) were generated. Then remote consultation over the 30 B-TTE studies was conducted by two experienced echocardiographic consultants while blinded to the OSR, and the corresponding remote consultation reports (RCR) were generated. Subsequently, the five frontline echocardiographers were convened together to discuss the difference between the OSR and RCR, and to confirm the correct interpretation and the misdiagnosis using a "majority-vote" consensus as the diagnostic "gold standard". Afterwards the reasons for the misdiagnosis were given by the frontline echocardiographers themselves. The inter-rater agreement between the OSR and the "gold standard" was assessed using Kappa coefficient and percent agreement. RESULTS: Complete correctness of the 30 copies of the RCR were determined by the 5 frontline echocardiographers. The reliability of the OSR in the findings of cardiac chamber dilation, left ventricular hypertrophy and pulmonary hypertension were weak (Kappa <0.6). The reliability of the OSR in the recognition of major cardiac abnormalities was very weak (Kappa =0.304, percent agreement =63.3%). Misdiagnosis of major abnormalities was found in 11 copies of OSR (11/30, 36.7%). CONCLUSIONS: The protocol of RC-B-TTE has shown noticeable superiority in ameliorating diagnostic accuracy of echocardiography, which should be generalized to clinical practice during the COVID-19 or similar pandemic.


Subject(s)
COVID-19 , Remote Consultation , Echocardiography , Humans , Pandemics , Reproducibility of Results , SARS-CoV-2
9.
Cell Res ; 31(7): 732-741, 2021 07.
Article in English | MEDLINE | ID: covidwho-1237995

ABSTRACT

SARS-CoV-2 variants could induce immune escape by mutations on the receptor-binding domain (RBD) and N-terminal domain (NTD). Here we report the humoral immune response to circulating SARS-CoV-2 variants, such as 501Y.V2 (B.1.351), of the plasma and neutralizing antibodies (NAbs) elicited by CoronaVac (inactivated vaccine), ZF2001 (RBD-subunit vaccine) and natural infection. Among 86 potent NAbs identified by high-throughput single-cell VDJ sequencing of peripheral blood mononuclear cells from vaccinees and convalescents, near half anti-RBD NAbs showed major neutralization reductions against the K417N/E484K/N501Y mutation combination, with E484K being the dominant cause. VH3-53/VH3-66 recurrent antibodies respond differently to RBD variants, and K417N compromises the majority of neutralizing activity through reduced polar contacts with complementarity determining regions. In contrast, the 242-244 deletion (242-244Δ) would abolish most neutralization activity of anti-NTD NAbs by interrupting the conformation of NTD antigenic supersite, indicating a much less diversity of anti-NTD NAbs than anti-RBD NAbs. Plasma of convalescents and CoronaVac vaccinees displayed comparable neutralization reductions against pseudo- and authentic 501Y.V2 variants, mainly caused by E484K/N501Y and 242-244Δ, with the effects being additive. Importantly, RBD-subunit vaccinees exhibit markedly higher tolerance to 501Y.V2 than convalescents, since the elicited anti-RBD NAbs display a high diversity and are unaffected by NTD mutations. Moreover, an extended gap between the third and second doses of ZF2001 leads to better neutralizing activity and tolerance to 501Y.V2 than the standard three-dose administration. Together, these results suggest that the deployment of RBD-vaccines, through a third-dose boost, may be ideal for combating SARS-CoV-2 variants when necessary, especially for those carrying mutations that disrupt the NTD supersite.


Subject(s)
Antibodies, Neutralizing/immunology , COVID-19 Vaccines/pharmacology , COVID-19/immunology , COVID-19/prevention & control , Immunity, Humoral , SARS-CoV-2/immunology , Vaccines, Inactivated/pharmacology , Animals , Antibodies, Neutralizing/blood , COVID-19/blood , COVID-19 Vaccines/immunology , Cell Line , HEK293 Cells , Humans , Models, Molecular , Mutation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Vaccines, Inactivated/immunology , Vaccines, Subunit/immunology , Vaccines, Subunit/pharmacology
10.
Vaccine ; 39(28): 3724-3730, 2021 06 23.
Article in English | MEDLINE | ID: covidwho-1233631

ABSTRACT

In order to meet the domestic urgent needs of evaluating the immunogenicity of vaccines and the potency testing of therapeutic antibody products against coronavirus disease 2019 (COVID-19), the first Chinese national standards for SARS-CoV-2 neutralizing antibody were established. The potency and stability of the candidate standards were determined by neutralization assay and accelerated degradation study. The stability studies showed that the standards were stable in the short-term. The collaborative study showed that the candidate standards could reduce the variations in neutralization titers between labs and thus improve comparability of neutralizing antibody measurements. Sample 22 has been approved by the Biological Product Reference Standards Sub-Committee of the National Drug Reference Standards Committee as the first Chinese National Standard for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) neutralizing antibody, with an assigned potency of 1,000 units per milliliter (U/ml). This standard will contribute to the standardized assessment of the quality and efficacy of vaccines and therapeutics for COVID-19 in China.


Subject(s)
Antibodies, Neutralizing , COVID-19 , Antibodies, Viral , China , Humans , Neutralization Tests , Reference Standards , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
12.
Neuropsychiatr Dis Treat ; 16: 2669-2675, 2020.
Article in English | MEDLINE | ID: covidwho-952562

ABSTRACT

Virtual reality exposure therapy (VRET) is becoming popular for treating phobia and anxiety disorder. The recent pandemic of COVID-19 not only causes infection per se but also has an impact on mental health. This case series aimed to explore the role of VRET in the intervention of psychiatric illnesses with chief complaints of fear of COVID-19 infection. In vivo exposure therapy for fear of COVID-19 infection is not possible due to the risk of virus infection; in this scenario, the VRET provides an immersive experience and can act as adjunctive therapy for treating phobias and anxiety disorders arising due to novel coronavirus pandemic. Clinical presentation and findings as well as management and procedures of VRET are discussed. Medical record of three patients (two male and one female) at the Shenzhen Mental Health Center (Shenzhen Kangning Hospital), China, was included in the present case series. Patients were assessed with the Hamilton Anxiety Rating Scale and Fear of COVID-19 Scale to measure anxiety and fear, respectively. Throughout VRET sessions, we gradually and systematically exposed the patient to virtual COVID-19 scenarios (for example, touching stained door handle which may have viruses, watching pandemic news, watching frontline health care workers, etc.). In our study, VRET intervention significantly reduced the related symptoms caused by fear of COVID-19 infection. Furthermore, virtual reality can provide relevant theoretical and practical support for exploring the remote psychological counseling of patients in isolation wards.

13.
Biosens Bioelectron ; 173: 112817, 2020 Nov 13.
Article in English | MEDLINE | ID: covidwho-935459

ABSTRACT

COVID-19 has evolved into a global pandemic. Early and rapid detection is crucial to control of the SARS-CoV-2 transmission. While representing the gold standard for early diagnosis, nucleic acid tests for SARS-CoV-2 are often complicated and time-consuming. Serological rapid antibody tests are characterized by high rates of false-negative diagnoses, especially during early infection. Here, we developed a novel nanozyme-based chemiluminescence paper assay for rapid and sensitive detection of SARS-CoV-2 spike antigen, which integrates nanozyme and enzymatic chemiluminescence immunoassay with the lateral flow strip. The core of our paper test is a robust Co-Fe@hemin-peroxidase nanozyme that catalyzes chemiluminescence comparable with natural peroxidase HRP and thus amplifies immune reaction signal. The detection limit for recombinant spike antigen of SARS-CoV-2 was 0.1 ng/mL, with a linear range of 0.2-100 ng/mL. Moreover, the sensitivity of test for pseudovirus could reach 360 TCID50/mL, which was comparable with ELISA method. The strip recognized SARS-CoV-2 antigen specifically, and there was no cross reaction with other coronaviruses or influenza A subtypes. This testing can be completed within 16 min, much shorter compared to the usual 1-2 h required for currently used nucleic acid tests. Furthermore, signal detection is feasible using the camera of a standard smartphone. Ingredients for nanozyme synthesis are simple and readily available, considerably lowering the overall cost. In conclusion, our paper test provides a high-sensitive point-of-care testing (POCT) approach for SARS-CoV-2 antigen detection, which should greatly facilitate early screening of SARS-CoV-2 infections, and considerably lower the financial burden on national healthcare resources.

15.
Dig Endosc ; 32(7): 1105-1110, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-780816

ABSTRACT

Endoscopy is widely used as a clinical diagnosis and treatment method for certain hepatobiliary and pancreatic diseases. However, due to the distinctive epidemiological characteristics of severe acute respiratory syndrome coronavirus 2, the virus causing coronavirus disease-2019 (COVID-19), healthcare providers are exposed to the patient's respiratory and gastrointestinal fluids, rendering endoscopy a high risk for transmitting a nosocomial infection. This article introduces preventive measures for endoscopic treatment enacted in our medical center during COVID-19, including the adjustment of indications, the application of endoscope protective equipment, the design and application of endoscopic masks and splash-proof films, and novel recommendations for bedside endoscope pre-sterilization.


Subject(s)
Coronavirus Infections/prevention & control , Cross Infection/prevention & control , Disease Transmission, Infectious/prevention & control , Endoscopes/standards , Endoscopy, Gastrointestinal/standards , Infection Control/standards , Masks , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Air Microbiology , Betacoronavirus , COVID-19 , China/epidemiology , Coronavirus Infections/epidemiology , Equipment Contamination/prevention & control , Hospital Units/standards , Humans , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Sterilization
18.
Nature ; 584(7819): 120-124, 2020 08.
Article in English | MEDLINE | ID: covidwho-381744

ABSTRACT

An outbreak of coronavirus disease 2019 (COVID-19)1-3, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)4, has spread globally. Countermeasures are needed to treat and prevent further dissemination of the virus. Here we report the isolation of two specific human monoclonal antibodies (termed CA1 and CB6) from a patient convalescing from COVID-19. CA1 and CB6 demonstrated potent SARS-CoV-2-specific neutralization activity in vitro. In addition, CB6 inhibited infection with SARS-CoV-2 in rhesus monkeys in both prophylactic and treatment settings. We also performed structural studies, which revealed that CB6 recognizes an epitope that overlaps with angiotensin-converting enzyme 2 (ACE2)-binding sites in the SARS-CoV-2 receptor-binding domain, and thereby interferes with virus-receptor interactions by both steric hindrance and direct competition for interface residues. Our results suggest that CB6 deserves further study as a candidate for translation to the clinic.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Angiotensin-Converting Enzyme 2 , Animals , Antibodies, Neutralizing/chemistry , Antibodies, Neutralizing/pharmacology , Antibodies, Viral/chemistry , Antibodies, Viral/pharmacology , Betacoronavirus/chemistry , Binding, Competitive , COVID-19 , Cell Line , Chlorocebus aethiops , Crystallization , Crystallography, X-Ray , Female , Humans , In Vitro Techniques , Macaca mulatta/immunology , Macaca mulatta/virology , Male , Models, Molecular , Neutralization Tests , Pandemics , Peptidyl-Dipeptidase A/chemistry , Peptidyl-Dipeptidase A/metabolism , Protein Binding/drug effects , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Spike Glycoprotein, Coronavirus/metabolism , Vero Cells , Viral Load/immunology
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