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1.
Mathematics ; 10(17):3046, 2022.
Article in English | MDPI | ID: covidwho-1997702

ABSTRACT

A SEIARN compartment model with the asymptomatic infection and secondary infection is proposed to predict the trend of COVID-19 more accurately. The model is extended according to the propagation characteristics of the novel coronavirus, the concepts of the asymptomatic infected compartment and secondary infection are introduced, and the contact rate parameters of the improved model are updated in real time by using the LSTM trajectory, in order to make accurate predictions. This SEIARN model first builds on the traditional SEIR compartment model, taking into account the asymptomatic infection compartment and secondary infection. Secondly, it considers the disorder of the trajectory and uses the improved LSTM model to predict the future trajectory of the current patients and cross-track with the susceptible patients to obtain the contact rate. Then, we conduct real-time updating of exposure rates in the SEIARN model and simulation of epidemic trends in Tianjin, Xi'an, and Shijiazhuang. Finally, the comparison experiments show that the SEIARN model performs better in prediction accuracy, MSE, and RMSE.

2.
Phys Chem Chem Phys ; 24(31): 18905-18914, 2022 Aug 10.
Article in English | MEDLINE | ID: covidwho-1972673

ABSTRACT

CD147 functions as the receptor of extracellular cyclophilin A (CypA) in various diseases, and CD147-CypA binding ulteriorly underlies the pathological process of various viral infections including HIV-1, SARS, and SARS-CoV-2. Although CyPA has been identified as a key intermediate pro-inflammatory factor, the mechanism by which CD147 cooperates with CypA in the development of the cytokine storm remains largely unknown, and the binding profile of CD147 with CypA remains to be elucidated as well. Here, we prepared three binding models of the CD147-CypA complex, including the active site of CypA severally binding to the groove bound by the Ig1 and Ig2 domains (model-0), P180-G181 (model-1), and P211 (model-2) of CD147, as well as introducing mutations P180A-G181A and P211A individually in each model. All systems were studied using accelerated molecular dynamics simulations and the molecular mechanics generalized Born surface area (MM/GBSA) method. For model-0, CypA bound to the ectodomain of CD147 with the highest binding affinity. Moreover, mutations P180A-G181A of CD147 in model-0 decreased the binding affinity and weakened the dynamic correlation between CD147 and CypA, which resulted in CypA shifting from the initial binding location. Other residue mutations of CD147 did not significantly affect the CD147-CypA binding, as reflected by the energy and structural analyses. Compared with surface plasmon resonance results and nuclear magnetic resonance shift signals, CypA should tend to reciprocally bind to the groove of CD147, and the binding process might be modulated by P180-G181 rather than P211. Besides, residue R201 of CD147 is critical for CD147-CypA binding and needs further experimental verification. These findings further our understanding of the recruitment between CD147 and CypA and its potential role in the development of inflammation and viral infection.


Subject(s)
COVID-19 , Cyclophilin A , Cyclophilin A/chemistry , Cyclophilin A/metabolism , Humans , Molecular Dynamics Simulation , SARS-CoV-2
3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324541

ABSTRACT

Background: Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) that began in Wuhan and rapidly spread globally. The speed and scope of spread of COVID-19 makes urgent of the defining clinical characteristics, serological and radiological changes of the affected patients. Method 7 patients with laboratory-confirmed COVID-19 who admitted to the Third affiliated hospital of Sun Yat-sen university Yuedong hospital from January 2020 to March 2020 were retrospectively enrolled and their clinical features, serological and radiological longitudinal changes were analyzed. Results Among the 7 patients, all (100%) had a clear epidemiological history. The most common symptoms were respiratory symptoms 6 (85.7%), and only 2 (28.6%) of the patients had fever at their first visit. The cohort included 4 (57.1%) common types and 3 (42.9%) severe types. Two (28.6%) common types patients developed to severe type in a short time. All of the 7 patients (100%) had abnormal liver function, normal renal function and normal procalcitonin. The detection time of specific antibody in 7 patients was 5~13d after symptoms. Before the specific antibody could be detected, the absolute value of lymphocytes decreased in 2 (28.6%) common type cases transferred to severe type cases accompanied with obvious progress in pulmonary imaging, and the phenomenon of decreased albumin and elevated globulin occurred in 6 patients (85.7%). The predominant pattern of lung lesions observed was bilateral (71.4%) and mainly near the pleura at the first diagnosis. Bilateral pulmonary involvement occurred in 6 cases (85.7%) during the course of disease. In 4 cases (57.1%) with obvious pulmonary lesions, the absolute value of lymphocytes decreased, albumin decreased and globulin increased during the course of the disease. Conclusion Serum specific antibodies can be detected within 2 weeks of onset. Close observation of the dynamic changes of absolute value of blood lymphocytes, serum albumin and globulin which were related to pulmonary imaging changes in patients will contribute to assessment of COVID-19.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324540

ABSTRACT

Background: Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) that began in Wuhan and rapidly spread globally. The speed and scope of spread of COVID-19 makes urgent of the defining clinical characteristics, serological and radiological changes of the affected patients. Method: 7 patients with laboratory-confirmed COVID-19 who admitted to the Third affiliated hospital of Sun Yat-sen university Yuedong hospital from January 2020 to March 2020 were retrospectively enrolled and their clinical features, serological and radiological longitudinal changes were analyzed . Results: Among the 7 patients, all (100%) had a clear epidemiological history. The most common symptoms were respiratory symptoms 6 (85.7%), and only 2 (28.6%) of the patients had fever at their first visit. The cohort included 4 (57.1%) common types and 3 (42.9%) severe types. Two (28.6%) common types patients developed to severe type in a short time. All of the 7 patients (100%) had abnormal liver function, normal renal function and normal procalcitonin. The detection time of specific antibody in 7 patients was 5~13d after symptoms. Before the specific antibody could be detected, the absolute value of lymphocytes decreased in 2 (28.6%) common type cases transferred to severe type cases accompanied with obvious progress in pulmonary imaging, and the phenomenon of decreased albumin and elevated globulin occurred in 6 patients (85.7%). The predominant pattern of lung lesions observed was bilateral (71.4%) and mainly near the pleura at the first diagnosis. Bilateral pulmonary involvement occurred in 6 cases (85.7%) during the course of disease. In 4 cases (57.1%) with obvious pulmonary lesions, the absolute value of lymphocytes decreased, albumin decreased and globulin increased during the course of the disease. Conclusion: Serum specific antibodies can be detected within 2 weeks of onset. Close observation of the dynamic changes of absolute value of blood lymphocytes, serum albumin and globulin which were related to pulmonary imaging changes in patients will contribute to assessment of COVID-19.

5.
J Cardiovasc Transl Res ; 15(1): 38-48, 2022 02.
Article in English | MEDLINE | ID: covidwho-1594479

ABSTRACT

Angiotensin-converting enzyme 2 (ACE2) is required for the cellular entry of the severe acute respiratory syndrome coronavirus 2. ACE2, via the Ang-(1-7)-Mas-R axis, is part of the antihypertensive and cardioprotective effects of the renin-angiotensin system. We studied hospitalized COVID-19 patients with hypertension and hypertensive human(h) ACE2 transgenic mice to determine the outcome of COVID-19 with or without AT1 receptor (AT1R) blocker treatment. The severity of the illness and the levels of serum cardiac biomarkers (CK, CK-BM, cTnI), as well as the inflammation markers (IL-1, IL-6, CRP), were lesser in hypertensive COVID-19 patients treated with AT1R blockers than those treated with other antihypertensive drugs. Hypertensive hACE2 transgenic mice, pretreated with AT1R blocker, had increased ACE2 expression and SARS-CoV-2 in the kidney and heart, 1 day post-infection. We conclude that those hypertensive patients treated with AT1R blocker may be at higher risk for SARS-CoV-2 infection. However, AT1R blockers had no effect on the severity of the illness but instead may have protected COVID-19 patients from heart injury, via the ACE2-angiotensin1-7-Mas receptor axis.


Subject(s)
COVID-19 , Hypertension , Animals , Humans , Hypertension/complications , Hypertension/drug therapy , Inpatients , Mice , Mice, Transgenic , Renin-Angiotensin System , SARS-CoV-2 , Virulence
6.
Molecules ; 26(23)2021 Dec 05.
Article in English | MEDLINE | ID: covidwho-1555019

ABSTRACT

SARS-CoV-2 is highly homologous to SARS-CoV. To date, the main protease (Mpro) of SARS-CoV-2 is regarded as an important drug target for the treatment of Coronavirus Disease 2019 (COVID-19). Some experiments confirmed that several HIV protease inhibitors present the inhibitory effects on the replication of SARS-CoV-2 by inhibiting Mpro. However, the mechanism of action has still not been studied very clearly. In this work, the interaction mechanism of four HIV protease inhibitors Darunavir (DRV), Lopinavir (LPV), Nelfinavir (NFV), and Ritonavire (RTV) targeting SARS-CoV-2 Mpro was explored by applying docking, molecular dynamics (MD) simulations, and MM-GBSA methods using the broad-spectrum antiviral drug Ribavirin (RBV) as the negative and nonspecific control. Our results revealed that LPV, RTV, and NFV have higher binding affinities with Mpro, and they all interact with catalytic residues His41 and the other two key amino acids Met49 and Met165. Pharmacophore model analysis further revealed that the aromatic ring, hydrogen bond donor, and hydrophobic group are the essential infrastructure of Mpro inhibitors. Overall, this study applied computational simulation methods to study the interaction mechanism of HIV-1 protease inhibitors with SARS-CoV-2 Mpro, and the findings provide useful insights for the development of novel anti-SARS-CoV-2 agents for the treatment of COVID-19.


Subject(s)
COVID-19/drug therapy , Coronavirus 3C Proteases/chemistry , Drug Design , HIV Protease Inhibitors/chemistry , Humans , Protein Binding
7.
Comb Chem High Throughput Screen ; 24(7): 1005-1006, 2021.
Article in English | MEDLINE | ID: covidwho-1328033
8.
Phys Chem Chem Phys ; 23(24): 13752-13759, 2021 Jun 28.
Article in English | MEDLINE | ID: covidwho-1270680

ABSTRACT

SARS-CoV-2 has recently caused an epidemic in humans and poses a huge threat to global public health. As a primary receptor of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2) exists in different hosts that are in close contact with humans, especially cats and dogs. However, the underlying mechanism of how the spike receptor binding domain (RBD) of SARS-CoV-2 cooperates with human ACE2 (hACE2), cat ACE2 (cACE2) and dog ACE2 (dACE2) and the variation in binding remains largely unsolved. Therefore, we explored the binding behavior of the spike RBD with cACE2, dACE2 and hACE2 via all-atom molecular dynamics simulations. In accordance with the binding free energies and residue interactions, the spike RBD has respective binding specificities with cACE2, dACE2 and hACE2, and the binding affinities decrease in the order of hACE2, cACE2, dACE2, mainly due to changes in the amino acids Q24L, H34Y, and M82T in cACE2 or dACE2. Furthermore, alanine scanning analysis results validated some key residues of the spike RBD interact with ACE2 and provided clues to the variation of amino acid that could influence the transmissibility or immune responses of SARS-CoV-2. Decreasing dynamic correlations strengths of ACE2 with the RBD were found in all hACE2-RBD, cACE2-RBD and dACE2-RBD systems. The ACE2 protein shows variable motion modes across the zinc metallopeptidase domain, which induces different interactions between ACE2 and the RBD. Our studies reveal that the motion pattern of the zinc metallopeptidase domain is critical to the binding behavior of RBD with ACE2. These findings could aid our understanding of selective recognition involving various ACE2 with the SARS-CoV-2 spike and shed further light on the binding mechanisms.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , SARS-CoV-2/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Angiotensin-Converting Enzyme 2/genetics , Animals , Cats , Dogs , Humans , Molecular Dynamics Simulation , Mutation , Principal Component Analysis , Protein Binding/genetics , Protein Domains/genetics , Spike Glycoprotein, Coronavirus/genetics , Thermodynamics
9.
Clin Lab ; 67(4)2021 Apr 01.
Article in English | MEDLINE | ID: covidwho-1190626

ABSTRACT

BACKGROUND: Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) began in Wuhan and rapidly spread globally. The speed and scope of the spread of COVID-19 makes it urgent to define clinical characteristics, serological and radiological changes of the affected patients. METHODS: Seven patients with laboratory-confirmed COVID-19 who were admitted to the Third Affiliated Hospital of Sun Yat-Sen University Yuedong Hospital from January 2020 to March 2020 were retrospectively enrolled and their clinical features, serological and radiological longitudinal changes were analyzed. RESULTS: Among the 7 patients, all (100%) had a clear epidemiological history. The most common symptoms were respiratory symptoms 6 (85.7%), and only 2 (28.6%) of the patients had fever at their first visit. The cohort included 4 (57.1%) common types and 3 (42.9%) severe types. Two (28.6%) common type patients developed to severe type in a short time. All of the 7 patients (100%) had abnormal liver function, normal renal function, and normal procalcitonin. The detection time of specific antibody in 7 patients was 5 - 13 days after symptoms. Before the specific antibody could be detected, the absolute value of lymphocytes decreased in 2 (28.6%) common type cases transferred to severe type cases accompanied with obvious progress in pulmonary imaging. The phenomenon of decreased albumin and elevated globulin occurred in 6 patients (85.7%). The predominant pattern of lung lesions observed was bilateral (71.4%) and mainly near the pleura at the first diagnosis. Bilateral pulmonary involvement occurred in 6 cases (85.7%) during the course of disease. In 4 cases (57.1%) with obvious pulmonary lesions, the absolute value of lymphocytes decreased, albumin decreased, and globulin increased during the course of the disease. CONCLUSIONS: Serum specific antibodies can be detected within 2 weeks of onset. Close observation of the dynamic changes of absolute value of blood lymphocytes, serum albumin, and globulin which were related to pulmonary imaging changes in patients will contribute to assessment of COVID-19.


Subject(s)
COVID-19/blood , COVID-19/diagnostic imaging , Antibodies, Viral/blood , China , Fever , Humans , Lung/diagnostic imaging , Lung/pathology , Lymphocyte Count , Retrospective Studies , Serum Albumin, Human/analysis , Serum Globulins/analysis
10.
Clin Lab ; 66(12)2020 Dec 01.
Article in English | MEDLINE | ID: covidwho-994192

ABSTRACT

BACKGROUND: Coronavirus disease (COVID-19) has affected more than 100 countries worldwide and the discharge criteria of patients with COVID-19 vary across different countries. In China, patients with two negative respiratory viral RNA tests taken at least one day apart can be discharged with no further quarantine required. Currently, PCR testing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in fecal sample is not routinely performed. METHODS: We present a patient with COVID-19, whose respiratory swabs became negative but fecal sample remained positive for SARS-CoV-2 RNA. RESULTS: Stool sample collected on 27th of February was still positive for SARS-CoV-2 RNA, 24 days after the first negative respiratory swab. CONCLUSIONS: Based on the experience from the 2003 SARS epidemic, we recommend that fecal RNA testing of SARS-CoV-2 should be incorporated into the discharge criteria to minimize the risk of transmission from the gastrointestinal tract.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19/virology , Convalescence , Feces/virology , Patient Discharge/standards , RNA, Viral/isolation & purification , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/isolation & purification , Adult , Antibodies, Viral/blood , Antiviral Agents/therapeutic use , Asymptomatic Infections , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/prevention & control , COVID-19 Serological Testing , Drug Therapy, Combination , False Negative Reactions , Female , Humans , Nasopharynx/virology , Pharynx/virology , Physical Distancing , SARS-CoV-2/immunology , Thymalfasin/therapeutic use
11.
Signal Transduct Target Ther ; 5(1): 283, 2020 12 04.
Article in English | MEDLINE | ID: covidwho-957563

ABSTRACT

In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2, no specific and effective drugs for treating this disease have been reported until today. Angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2, mediates the virus infection by binding to spike protein. Although ACE2 is expressed in the lung, kidney, and intestine, its expressing levels are rather low, especially in the lung. Considering the great infectivity of COVID-19, we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection. Here, we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein. The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody, Meplazumab, inhibits SARS-CoV-2 amplification. Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells, which can be neutralized by CD147 extracellular fragment. Viral loads are detectable in the lungs of human CD147 (hCD147) mice infected with SARS-CoV-2, but not in those of virus-infected wild type mice. Interestingly, virions are observed in lymphocytes of lung tissue from a COVID-19 patient. Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dose-dependent manner, which is specifically inhibited by Meplazumab. Furthermore, CD147 mediates virus entering host cells by endocytosis. Together, our study reveals a novel virus entry route, CD147-spike protein, which provides an important target for developing specific and effective drug against COVID-19.


Subject(s)
Basigin/genetics , COVID-19/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Basigin/immunology , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , Host-Pathogen Interactions/immunology , Humans , Lung/immunology , Lung/pathology , Lung/virology , Mice , Pandemics , Protein Binding/immunology , Protein Domains/genetics , Protein Domains/immunology , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/genetics , Virus Internalization
12.
Chin. Phys. Lett. ; 5(37)20200501.
Article in English | WHO COVID, ELSEVIER | ID: covidwho-679720

ABSTRACT

Coronavirus Disease 2019 (COVID-19), caused by the novel coronavirus, has spread rapidly across China. Consequently, there is an urgent need to sort and develop novel agents for the prevention and treatment of viral infections. A rapid structure-based virtual screening is used for the evaluation of current commercial drugs, with structures of human angiotensin converting enzyme II (ACE2), and viral main protease, spike, envelope, membrane and nucleocapsid proteins. Our results reveal that the reported drugs Arbidol, Chloroquine and Remdesivir may hinder the entry and release of virions through the bindings with ACE2, spike and envelope proteins. Due to the similar binding patterns, NHC (β-d-N4-hydroxycytidine) and Triazavirin are also in prospects for clinical use. Main protease (3CLpro) is likely to be a feasible target of drug design. The screening results to target 3CL-pro reveal that Mitoguazone, Metformin, Biguanide Hydrochloride, Gallic acid, Caffeic acid, Sulfaguanidine and Acetylcysteine seem be possible inhibitors and have potential application in the clinical therapy of COVID-19.

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