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1.
Virol Sin ; 2022 Jun 01.
Article in English | MEDLINE | ID: covidwho-1867891

ABSTRACT

SARS-CoV-2 infection is a global public health threat. Vaccines are considered amongst the most important tools to control the SARS-CoV-2 pandemic. As expected, deaths from SARS-CoV-2 infection have dropped dramatically with widespread vaccination. However, there are concerns over the duration of vaccine-induced protection, as well as their effectiveness against emerging variants of concern. Here, we constructed a recombinant chimpanzee adenovirus vectored vaccine expressing the full-length spike of SARS-CoV-2 (AdC68-S). Rapid and high levels of humoral and cellular immune responses were observed after immunization of C57BL/6J mice with one or two doses of AdC68-S. Notably, neutralizing antibodies were observed up to at least six months after vaccination, without substantial decline. Single or double doses AdC68-S immunization resulted in lower viral loads in lungs of mice against SARS-CoV-2 challenge both in the short term (21 days) and long-term (6 months). Histopathological examination of AdC68-S immunized mice lungs showed mild histological abnormalities after SARS-CoV-2 infection. Taken together, this study demonstrates the efficacy and durability of the AdC68-S vaccine and constitutes a promising candidate for clinical evaluation.

2.
Atmosphere ; 13(5):842, 2022.
Article in English | MDPI | ID: covidwho-1857308

ABSTRACT

Mass suspension of anthropogenic activities is extremely rare, the quarantine due to the coronavirus disease 2019 (COVID-19) represents a natural experiment to investigate the impact of anthropogenic activities on air quality. The mitigation of air pollution during the COVID-19 lockdown has been reported from a global perspective;however, the air pollution levels vary in different regions. This study initiated a novel synthesis of multiple-year satellite observations, national ground measurements towards SO2, NO2 and O3 and meteorological conditions to evaluate the impact of the COVID-19 lockdown in Beihai, a specific city in a less developed area in southwest China, to reveal the potential implications of control strategies for air pollution. The levels of the major air pollutants during the COVID-19 lockdown (LP) and during the same period of previous years (SP) were compared and a series of statistical tools were applied to analyze the sources of air pollution in Beihai. The results show that air pollutant levels decreased with substantial diversity during the LP. Satellite-retrieved NO2 and SO2 levels during the LP decreased by 5.26% and 22.06%, while NO2, SO2, PM2.5 and PM10 from ground measurements during the LP were 25.6%, 2.7%, 22.2% and 22.2% lower than during SP, respectively. Ground measured SO2 concentrations during the LP were only 2.7% lower than during the SP, which may be attributed to uninterrupted essential industrial activities, such as power plants. Polar plots analysis shows that NO2 concentrations were strongly associated with local emission sources, such as automobiles and local industry. Additionally, the much lower levels of NO2 concentrations during the LP and the absence of an evening peak may highlight the significant impact of the traffic sector on NO2. The decrease in daily mean O3 concentrations during the LP may be associated with the reduction in NO2 concentrations. Indications in this study could be beneficial for the formulation of atmospheric protection policies.

3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-336878

ABSTRACT

The global emergence of SARS-CoV-2 variants has led to increasing breakthrough infections in vaccinated populations, calling for an urgent need to develop more effective and broad-spectrum vaccines to combat COVID-19. Here we report the preclinical development of RQ3013, an mRNA vaccine candidate intended to bring broad protection against SARS-CoV-2 variants of concern (VOCs). RQ3013, which contains pseudouridine-modified mRNAs formulated in lipid nanoparticles, encodes the spike(S) protein harboring a combination of mutations responsible for immune evasion of VOCs. Here we characterized the expressed S immunogen and evaluated the immunogenicity, efficacy, and safety of RQ3013 in various animal models. RQ3013 elicited robust immune responses in mice, hamsters, and nonhuman primates (NHP). It can induce high titers of antibodies with broad cross-neutralizing ability against the Wild-type, B.1.1.7, B.1.351, B.1.617.2, and the omicron B.1.1.529 variants. In mice and NHP, two doses of RQ3013 protected the upper and lower respiratory tract against infection by SARS-CoV-2 and its variants. We also proved the safety of RQ3013 in NHP models. Our results provided key support for the evaluation of RQ3013 in clinical trials.

4.
Biosens Bioelectron ; 209: 114226, 2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1767929

ABSTRACT

Protein sensors based on allosteric enzymes responding to target binding with rapid changes in enzymatic activity are potential tools for homogeneous assays. However, a high signal-to-noise ratio (S/N) is difficult to achieve in their construction. A high S/N is critical to discriminate signals from the background, a phenomenon that might largely vary among serum samples from different individuals. Herein, based on the modularized luciferase NanoLuc, we designed a novel biosensor called NanoSwitch. This sensor allows direct detection of antibodies in 1 µl serum in 45 min without washing steps. In the detection of Flag and HA antibodies, NanoSwitches respond to antibodies with S/N ratios of 33-fold and 42-fold, respectively. Further, we constructed a NanoSwitch for detecting SARS-CoV-2-specific antibodies, which showed over 200-fold S/N in serum samples. High S/N was achieved by a new working model, combining the turn-off of the sensor with human serum albumin and turn-on with a specific antibody. Also, we constructed NanoSwitches for detecting antibodies against the core protein of hepatitis C virus (HCV) and gp41 of the human immunodeficiency virus (HIV). Interestingly, these sensors demonstrated a high S/N and good performance in the assays of clinical samples; this was partly attributed to the combination of off-and-on models. In summary, we provide a novel type of protein sensor and a working model that potentially guides new sensor design with better performance.


Subject(s)
Biosensing Techniques , COVID-19 , Antibodies, Viral , COVID-19/diagnosis , Humans , Luciferases , SARS-CoV-2
6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-311717

ABSTRACT

The Coronavirus Disease of 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health and economy. Therapeutic options such as monoclonal antibodies (mAbs) against SARS-CoV-2 are in urgent need. We have identified potent monoclonal antibodies binding to SARS-CoV-2 Spike protein from COVID-19 convalescent patients and one of these antibodies, P4A1, interacts directly and covers the majority of the Receptor Binding Motif (RBM) of Spike receptor-binding domain (RBD), shown by high-resolution complex structure analysis. We further demonstrated P4A1 binding and neutralizing activities against wild type and mutant spike proteins. P4A1 was subsequently engineered to reduce the potential risk for antibody-dependent enhancement (ADE) of infection and to extend its half-life. The engineered mAb exhibits optimized pharmacokinetic and safety profile, and results in complete viral clearance in a rhesus monkey model of COVID-19 following a single injection.

8.
Cell Discov ; 7(1): 82, 2021 Sep 07.
Article in English | MEDLINE | ID: covidwho-1397862

ABSTRACT

The pandemic of COVID-19 caused by SARS-CoV-2 has raised a new challenges to the scientific and industrious fields after over 1-year spread across different countries. The ultimate approach to end the pandemic is the timely application of vaccines to achieve herd immunity. Here, a novel SARS-CoV-2 receptor-binding domain (RBD) homodimer was developed as a SARS-CoV-2 vaccine candidate. Formulated with aluminum adjuvant, RBD dimer elicited strong immune response in both rodents and non-human primates, and protected mice from SARS-CoV-2 challenge with significantly reducing viral load and alleviating pathological injury in the lung. In the non-human primates, the vaccine could prevent majority of the animals from SARS-CoV-2 infection in the respiratory tract and reduce lung damage. In addition, antibodies elicited by this vaccine candidate showed cross-neutralization activities to SARS-CoV-2 variants. Furthermore, with our expression system, we provided a high-yield RBD homodimer vaccine without additional biosafety or special transport device supports. Thus, it may serve as a safe, effective, and low-cost SARS-CoV-2 vaccine candidate.

9.
MAbs ; 13(1): 1930636, 2021.
Article in English | MEDLINE | ID: covidwho-1258715

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease-2019 (COVID-19), interacts with the host cell receptor angiotensin-converting enzyme 2 (hACE2) via its spike 1 protein during infection. After the virus sequence was published, we identified two potent antibodies against the SARS-CoV-2 receptor binding domain (RBD) from antibody libraries using a phage-to-yeast (PtY) display platform in only 10 days. Our lead antibody JMB2002, now in a Phase 1 clinical trial (ChiCTR2100042150), showed broad-spectrum in vitro blocking activity against hACE2 binding to the RBD of multiple SARS-CoV-2 variants, including B.1.351 that was reportedly much more resistant to neutralization by convalescent plasma, vaccine sera and some clinical-stage neutralizing antibodies. Furthermore, JMB2002 has demonstrated complete prophylactic and potent therapeutic efficacy in a rhesus macaque disease model. Prophylactic and therapeutic countermeasure intervention of SARS-CoV-2 using JMB2002 would likely slow down the transmission of currently emerged SARS-CoV-2 variants and result in more efficient control of the COVID-19 pandemic.


Subject(s)
Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Antibodies, Neutralizing/pharmacology , Antiviral Agents/pharmacology , COVID-19/drug therapy , COVID-19/prevention & control , SARS-CoV-2/drug effects , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/immunology , Animals , Antibody Specificity , Binding Sites, Antibody , CHO Cells , COVID-19/immunology , COVID-19/metabolism , COVID-19/virology , Chlorocebus aethiops , Cricetulus , Disease Models, Animal , Epitopes , Macaca mulatta , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Vero Cells
10.
Nat Commun ; 12(1): 2623, 2021 05 11.
Article in English | MEDLINE | ID: covidwho-1225506

ABSTRACT

COVID-19 pandemic caused by SARS-CoV-2 constitutes a global public health crisis with enormous economic consequences. Monoclonal antibodies against SARS-CoV-2 can provide an important treatment option to fight COVID-19, especially for the most vulnerable populations. In this work, potent antibodies binding to SARS-CoV-2 Spike protein were identified from COVID-19 convalescent patients. Among them, P4A1 interacts directly with and covers majority of the Receptor Binding Motif of the Spike Receptor-Binding Domain, shown by high-resolution complex structure analysis. We further demonstrate the binding and neutralizing activities of P4A1 against wild type and mutant Spike proteins or pseudoviruses. P4A1 was subsequently engineered to reduce the potential risk for Antibody-Dependent Enhancement of infection and to extend its half-life. The engineered antibody exhibits an optimized pharmacokinetic and safety profile, and it results in complete viral clearance in a rhesus monkey model of COVID-19 following a single injection. These data suggest its potential against SARS-CoV-2 related diseases.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Monoclonal/metabolism , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/chemistry , Antibodies, Neutralizing/metabolism , Antibodies, Viral/metabolism , Antibody Specificity/immunology , COVID-19/drug therapy , COVID-19/epidemiology , Cell Line, Tumor , Cells, Cultured , Chlorocebus aethiops , Female , Humans , Macaca mulatta , Male , Mutation , Pandemics , Protein Binding , Protein Domains , SARS-CoV-2/drug effects , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Treatment Outcome , Vero Cells
11.
Environ Sci Pollut Res Int ; 28(33): 45344-45352, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1188153

ABSTRACT

To control the spread of COVID-19, China has imposed national lockdown policies to restrict the movement of its population since the Chinese New Year of January 2020. In this study, we quantitatively analyzed the changes of pollution sources in Shanghai during the COVID-19 lockdown; a high-resolution emission inventory of typical pollution sources including stationary source, mobile source, and oil and gas storage and transportation source was established based on pollution source data from January to February 2020. The results show that the total emissions of sulfur dioxide (SO2), nitrogen oxides (NOx), particulate matter (PM), and volatile organic compounds (VOCs) were 9520.2, 37,978.6, 2796.7, and 7236.9 tons, respectively, during the study period. Affected by the COVID-19 lockdown, the mobile source experienced the largest decline. The car mileage and oil sales decreased by about 80% during the COVID-19 lockdown (P3) when compared with those during the pre-Spring Festival (P1). The number of aircraft activity decreased by approximately 50%. The impact of the COVID-19 epidemic on industries such as iron and steel and petrochemicals was less significant, while the greater impact was on coatings, chemicals, rubber, and plastic. The emissions of SO2, NOx, PM2.5, and VOCs decreased by 11%, 39%, 37%, and 47%, respectively, during P3 when compared with those during P1. The results show that the measures to control the spread of the COVID-19 epidemic made a significant contribution to emission reductions. This study may provide a reference for other countries to assess the impact of the COVID-19 epidemic on emissions and help establish regulatory actions to improve air quality.


Subject(s)
Air Pollutants , Air Pollution , COVID-19 , Air Pollutants/analysis , Air Pollution/analysis , China , Communicable Disease Control , Environmental Monitoring , Humans , Particulate Matter/analysis , SARS-CoV-2
12.
Virol Sin ; 36(5): 879-889, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1174014

ABSTRACT

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused more than 96 million infections and over 2 million deaths worldwide so far. However, there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the disease causative agent. Vaccine is the most effective approach to eradicate a pathogen. The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations. Here we evaluated the safety, immunogenicity, and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates. Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates, and subsequently provided partial (in low dose) or full (in high dose) protection of challenge in the tested animals. In addition, passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice. These results warranted positive outcomes in future clinical trials in humans.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19 , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/prevention & control , Mice , Mice, Transgenic , Primates , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccines, Inactivated/immunology
13.
J Environ Sci (China) ; 106: 26-38, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1046321

ABSTRACT

To investigate the air quality change during the COVID-19 pandemic, we analyzed spatiotemporal variations of six criteria pollutants in nine typical urban agglomerations in China using ground-based data and examined meteorological influences through correlation analysis and backward trajectory analysis under different responses. Concentrations of PM2.5, PM10, NO2, SO2 and CO in urban agglomerations respectively decreased by 18%-45% (30%-62%), 17%-53% (22%-39%), 47%-64% (14%-41%), 9%-34% (0%-53%) and 16%-52% (23%-56%) during Lockdown (Post-lockdown) period relative to Pre-lockdown period. PM2.5 pollution events occurred during Lockdown in Beijing-Tianjin-Hebe (BTH) and Middle and South Liaoning (MSL), and daily O3 concentration rose to grade Ⅱ standard in Post-lockdown period. Distinct from the nationwide slump of NO2 during Lockdown period, a rebound (∼40%) in Post-lockdown period was observed in Cheng-Yu (CY), Yangtze River Middle-Reach (YRMR), Yangtze River Delta (YRD) and Pearl River Delta (PRD). With slightly higher wind speed compared with 2019, the reduction of PM2.5 (51%-62%) in Post-lockdown period is more than 2019 (15%-46%) in HC (Harbin-Changchun), MSL, BTH, CP (Central Plain) and SP (Shandong-Peninsula), suggesting lockdown measures are effective to PM2.5 alleviation. Although O3 concentrations generally increased during the lockdown, its increment rate declined compared with 2019 under similar sunlight duration and temperature. Additionally, unlike HC, MSL and BTH, which suffered from additional (> 30%) air masses from surrounding areas after the lockdown, the polluted air masses reaching YRD and PRD mostly originated from the long-distance transport, highlighting the importance of joint regional governance.


Subject(s)
Air Pollutants , Air Pollution , COVID-19 , Air Pollutants/analysis , Air Pollution/analysis , Beijing , China , Cities , Communicable Disease Control , Environmental Monitoring , Humans , Pandemics , Particulate Matter/analysis , SARS-CoV-2
14.
Nat Commun ; 11(1): 5752, 2020 11 13.
Article in English | MEDLINE | ID: covidwho-926678

ABSTRACT

Efficacious interventions are urgently needed for the treatment of COVID-19. Here, we report a monoclonal antibody (mAb), MW05, with SARS-CoV-2 neutralizing activity by disrupting the interaction of receptor binding domain (RBD) with angiotensin-converting enzyme 2 (ACE2) receptor. Crosslinking of Fc with FcγRIIB mediates antibody-dependent enhancement (ADE) activity by MW05. This activity is eliminated by introducing the LALA mutation to the Fc region (MW05/LALA). Potent prophylactic and therapeutic effects against SARS-CoV-2 are observed in rhesus monkeys. A single dose of MW05/LALA blocks infection of SARS-CoV-2 in prophylactic treatment and clears SARS-CoV-2 in three days in a therapeutic treatment setting. These results pave the way for the development of MW05/LALA as an antiviral strategy for COVID-19.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antiviral Agents/pharmacology , Betacoronavirus/immunology , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Spike Glycoprotein, Coronavirus/immunology , Angiotensin-Converting Enzyme 2 , Animals , Antibodies, Viral/immunology , COVID-19 , Cell Line , Chlorocebus aethiops , Coronavirus Infections/prevention & control , Female , HEK293 Cells , Humans , Macaca mulatta , Male , Pandemics/prevention & control , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/prevention & control , Receptors, IgG/genetics , Receptors, IgG/immunology , Receptors, Virus/metabolism , SARS-CoV-2 , Vero Cells , Virus Attachment
15.
Environ Pollut ; 267: 115612, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-753608

ABSTRACT

To investigate chemical characteristics, abatement mechanisms and regional transport of atmospheric pollutants during the COVID-19 outbreak control period in the Yangtze River Delta (YRD) region, China, the measurements of air pollutants including fine particulate matter (PM2.5) and volatile organic compounds (VOCs) on non-control period (NCP, 24 December 2019-23 January 2020) and control period (CP, 24 January-23 February 2020) were analyzed at the urban Pudong Supersite (PD) and the regional Dianshan Lake Supersite (DSL). Due to the stricter outbreak control, the levels of PM2.5 and VOCs, and the occurrence frequencies of haze-fog episodes decreased substantially from NCP to CP, with average reduction rates of 31.6%, 38.9% and 35.1% at PD, and 34.5%, 50.7% and 37.9% at DSL, respectively. The major source for PM2.5 was secondary sulfate & nitrate in both periods, and the emission control of primary sources such as coal burning and vehicle exhaust decreased the levels of precursors gas sulfur dioxide and nitrogen oxide, which highly contributed to the abatement of PM2.5 from NCP to CP. The higher levels of ozone at both PD and DSL on CP might be due to the weak nitrogen monoxide titration, low relative humidity and high visibility compared with NCP. Vehicle exhaust and fugitive emission from petrochemical industry were the major contributors of ambient VOCs and their decreasing activities mainly accounted for VOCs abatement. Moreover, the high frequency of haze-fog events was closely impacted by medium-scale regional transport within Anhui and Jiangsu provinces. Therefore, the decreasing regional transported air pollutants coincided with the emission control of local sources to cause the abatement of haze-fog events in YRD region on CP. This study could improve the understanding of the change of atmospheric pollutants during the outbreak control period, and provide scientific base for haze-fog pollution control in YRD region, China.


Subject(s)
Air Pollutants , Air Pollution , COVID-19 , Environmental Pollutants , China , Disease Outbreaks , Environmental Monitoring , Humans , Pandemics , Particulate Matter , Seasons
16.
Cell Res ; 30(8): 670-677, 2020 08.
Article in English | MEDLINE | ID: covidwho-637104

ABSTRACT

The 2019 novel coronavirus (SARS-CoV-2) outbreak is a major challenge for public health. SARS-CoV-2 infection in human has a broad clinical spectrum ranging from mild to severe cases, with a mortality rate of ~6.4% worldwide (based on World Health Organization daily situation report). However, the dynamics of viral infection, replication and shedding are poorly understood. Here, we show that Rhesus macaques are susceptible to the infection by SARS-CoV-2. After intratracheal inoculation, the first peak of viral RNA was observed in oropharyngeal swabs one day post infection (1 d.p.i.), mainly from the input of the inoculation, while the second peak occurred at 5 d.p.i., which reflected on-site replication in the respiratory tract. Histopathological observation shows that SARS-CoV-2 infection can cause interstitial pneumonia in animals, characterized by hyperemia and edema, and infiltration of monocytes and lymphocytes in alveoli. We also identified SARS-CoV-2 RNA in respiratory tract tissues, including trachea, bronchus and lung; and viruses were also re-isolated from oropharyngeal swabs, bronchus and lung, respectively. Furthermore, we demonstrated that neutralizing antibodies generated from the primary infection could protect the Rhesus macaques from a second-round challenge by SARS-CoV-2. The non-human primate model that we established here provides a valuable platform to study SARS-CoV-2 pathogenesis and to evaluate candidate vaccines and therapeutics.


Subject(s)
Betacoronavirus/genetics , Betacoronavirus/immunology , Coronavirus Infections/pathology , Disease Models, Animal , Macaca mulatta/virology , Pneumonia, Viral/pathology , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/virology , Female , Immunohistochemistry , Male , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/virology , RNA, Viral/genetics , Radiography, Thoracic , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , Viral Load , Virus Replication
17.
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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