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1.
Front Microbiol ; 13: 884034, 2022.
Article in English | MEDLINE | ID: covidwho-1847188

ABSTRACT

Since the outbreak of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), public health worldwide has been greatly threatened. The development of an effective treatment for this infection is crucial and urgent but is hampered by the incomplete understanding of the viral infection mechanisms and the lack of specific antiviral agents. We previously reported that teicoplanin, a glycopeptide antibiotic that has been commonly used in the clinic to treat bacterial infection, significantly restrained the cell entry of Ebola virus, SARS-CoV, and MERS-CoV by specifically inhibiting the activity of cathepsin L (CTSL). Here, we found that the cleavage sites of CTSL on the spike proteins of SARS-CoV-2 were highly conserved among all the variants. The treatment with teicoplanin suppressed the proteolytic activity of CTSL on spike and prevented the cellular infection of different pseudotyped SARS-CoV-2 viruses. Teicoplanin potently prevented the entry of SARS-CoV-2 into the cellular cytoplasm with an IC50 of 2.038 µM for the Wuhan-Hu-1 reference strain and an IC50 of 2.116 µM for the SARS-CoV-2 (D614G) variant. The pre-treatment of teicoplanin also prevented SARS-CoV-2 infection in hACE2 mice. In summary, our data reveal that CTSL is required for both SARS-CoV-2 and SARS-CoV infection and demonstrate the therapeutic potential of teicoplanin for universal anti-CoVs intervention.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-334259

ABSTRACT

We found four striking differences in the COVID-19 case fatality rate (CFR) or the ratio of symptomatic COVID-19 cases versus asymptomatic infections. These striking differences all suggest that the risk for China to move away from its zero-COVID policy shall depend on China’s control measures. The CFR of COVID-19 in China can remain less than one tenth of influenza, namely that COVID-19 can be “tiny influenza”in China, if COVID-19 cases shall be well isolated in well disinfected environments (e.g., staying at well-disinfected home) with good maintenance treatment, to minimize their co-infections and maintain their body functions. Otherwise, the CFR of COVID-19 in China can be several times higher than influenza, namely that COVID-19 can be “giant influenza”in China. This analysis is also important to mitigate COVID-19 worldwide.

3.
Signal Transduct Target Ther ; 7(1): 114, 2022 04 05.
Article in English | MEDLINE | ID: covidwho-1778593

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel coronavirus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor-binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo. Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS-CoV-2 vaccine.


Subject(s)
Antibodies, Monoclonal , Antibodies, Viral , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Antibodies, Monoclonal/chemistry , Antibodies, Viral/chemistry , COVID-19 , Cryoelectron Microscopy , Humans , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology
4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315251

ABSTRACT

Background: While great success in the coronavirus disease 2019 (COVID-19) control has been achieved in China, imported cases have become a major challenge. This study aimed to describe the epidemiological and clinical characteristics of imported COVID-19 cases and to assess the effectiveness of screening strategy in Beijing, China. Methods This retrospective study included all imported COVID-19 cases from Beijing Ditan Hospital from 29 February to 20 March 2020, who were screened by both chest computed tomography (CT) and reverse-transcriptase-polymerase chain reaction (RT-PCR) at initial presentation. Demographic, clinical and laboratory data, in addition to chest CT imaging were were collected and analyzed. Results A total of 71 imported cases were finally diagnosed with laboratory-confirmed COVID-19. The cases were mainly acquired from Europe (63 cases, 88.73%). The main clinical manifestations were fever and cough, which accounted for 30 cases (42.25%) and 35 cases (49.30%), respectively. Only 4 cases (5.63%) had lymphocytopenia and 13 (18.31%) cases demonstrated elevated levels of C-reactive protein (CRP). All cases had normal serum levels of procalcitonin (PCT). 35 cases (49.30%) had abnormal CT findings at initial presentation, whereas 36 cases (50.70%) had a normal CT. Using RT-PCR, 59 cases (83.10%) were tested positive at initial presentation. Conclusions The number of overseas imported COVID-19 cases continues to rise in China. The combination of screening tools, particularly CT and RT-PCR, can detect imported COVID-19 cases efficiently.

5.
Chem Commun (Camb) ; 58(11): 1804-1807, 2022 Feb 03.
Article in English | MEDLINE | ID: covidwho-1639537

ABSTRACT

We present the finding of a dimeric ACE2 peptide mimetic designed through side chain cross-linking and covalent dimerization. It has a binding affinity of 16 nM for the SARS-CoV-2 spike RBD, and effectively inhibits the SARS-CoV-2 pseudovirus in Huh7-hACE2 cells with an IC50 of 190 nM and neutralizes the authentic SARS-CoV-2 in Caco2 cells with an IC50 of 2.4 µM. Our study should provide a new insight for the optimization of peptide-based anti-SARS-CoV-2 inhibitors.


Subject(s)
Antiviral Agents/pharmacology , Peptide Fragments/pharmacology , Peptidomimetics/pharmacology , SARS-CoV-2/drug effects , Amino Acid Sequence , Angiotensin-Converting Enzyme 2/chemistry , Antiviral Agents/chemical synthesis , Antiviral Agents/metabolism , Cell Line, Tumor , Humans , Microbial Sensitivity Tests , Peptide Fragments/chemical synthesis , Peptide Fragments/metabolism , Peptidomimetics/chemical synthesis , Peptidomimetics/metabolism , Protein Binding , Protein Domains , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism
6.
BMC Infect Dis ; 22(1): 59, 2022 Jan 17.
Article in English | MEDLINE | ID: covidwho-1634635

ABSTRACT

BACKGROUND: In March 2020, the WHO declared the novel coronavirus outbreak a global pandemic. While great success in coronavirus disease 2019 (COVID-19) control has been achieved in China, imported cases have become a major challenge. This study aimed to describe the epidemiological and clinical characteristics of imported COVID-19 cases and to assess the effectiveness of screening strategies in Beijing, China. METHODS: This retrospective study included all imported cases transferred to Beijing Ditan Hospital from 29 February to 20 March 2020 who were screened by both chest computed tomography (CT) and reverse-transcriptase-polymerase chain reaction (RT-PCR) at the initial presentation. Demographic, clinical and laboratory data, in addition to chest CT imaging, were collected and analysed. RESULTS: In total, 2545 cases were included, among which 71 (2.8%) were finally diagnosed with laboratory-confirmed COVID-19. The majority 63 (88.7%) were from Europe. The most common initial symptoms were cough and fever, which accounted for 49.3% and 42.3%, respectively. Only four cases (5.6%) had lymphocytopenia, and thirteen cases (18.3%) demonstrated elevated levels of C-reactive protein (CRP). All cases had normal serum levels of procalcitonin (PCT). At initial presentation, among the 71 confirmed cases, 59 (83.1%) had a positive RT-PCR assay, and 35 (49.3%) had a positive chest CT. Twelve (16.9%) had a negative RT-PCR assay but a positive chest CT. CONCLUSIONS: A combination of RT-PCR and chest CT is an effective strategy for the screening of imported COVID-19 cases. Our findings provide important information and clinical evidence about the infection control of imported COVID-19 cases.


Subject(s)
COVID-19 , Beijing/epidemiology , China/epidemiology , Humans , Pandemics , Retrospective Studies , SARS-CoV-2
7.
Curr Opin Virol ; 53: 101199, 2022 04.
Article in English | MEDLINE | ID: covidwho-1588012

ABSTRACT

The pandemic of Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome 2 coronavirus (SARS-CoV-2) is a continuing worldwide threat to human health and social economy. Historically, SARS-CoV-2 follows SARS and MERS as the third coronavirus spreading across borders and continents, but far more dangerous with long-lasting symptomatic consequences. The current situation is strong evidence that coronaviruses will continue to be pathogens of consequence in the future, thus calling for the development of neutralizing antibody-based prophylactics and therapeutics for prevention and treatment of COVID-19 and other human coronavirus diseases. This review summarized the progresses of developing neutralizing monoclonal antibodies against infection of SARS-CoV-2, SARS-CoV, and MERS-CoV, and discussed their potential applications in prevention and treatment of COVID-19 and other human coronavirus diseases.


Subject(s)
COVID-19 , Middle East Respiratory Syndrome Coronavirus , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/therapeutic use , Humans , SARS-CoV-2
8.
Signal Transduct Target Ther ; 6(1): 420, 2021 12 14.
Article in English | MEDLINE | ID: covidwho-1585885

ABSTRACT

COVID-19 is identified as a zoonotic disease caused by SARS-CoV-2, which also can cross-transmit to many animals but not mice. Genetic modifications of SARS-CoV-2 or mice enable the mice susceptible to viral infection. Although neither is the natural situation, they are currently utilized to establish mouse infection models. Here we report a direct contact transmission of SARS-CoV-2 variant B.1.351 in wild-type mice. The SARS-CoV-2 (B.1.351) replicated efficiently and induced significant pathological changes in lungs and tracheas, accompanied by elevated proinflammatory cytokines in the lungs and sera. Mechanistically, the receptor-binding domain (RBD) of SARS-CoV-2 (B.1.351) spike protein turned to a high binding affinity to mouse angiotensin-converting enzyme 2 (mACE2), allowing the mice highly susceptible to SARS-CoV-2 (B.1.351) infection. Our work suggests that SARS-CoV-2 (B.1.351) expands the host range and therefore increases its transmission route without adapted mutation. As the wild house mice live with human populations quite closely, this possible transmission route could be potentially risky. In addition, because SARS-CoV-2 (B.1.351) is one of the major epidemic strains and the mACE2 in laboratory-used mice is naturally expressed and regulated, the SARS-CoV-2 (B.1.351)/mice could be a much convenient animal model system to study COVID-19 pathogenesis and evaluate antiviral inhibitors and vaccines.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , COVID-19/transmission , Host-Pathogen Interactions/genetics , Receptors, Virus/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Angiotensin-Converting Enzyme 2/immunology , Animals , COVID-19/immunology , COVID-19/virology , Cytokines/genetics , Cytokines/immunology , Disease Models, Animal , Gene Expression , HEK293 Cells , Host-Pathogen Interactions/immunology , Humans , Lung/pathology , Lung/virology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Protein Binding , Protein Domains , Receptors, Virus/immunology , SARS-CoV-2/classification , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/immunology , Virus Replication
9.
Clin Chim Acta ; 524: 132-138, 2022 Jan 01.
Article in English | MEDLINE | ID: covidwho-1576025

ABSTRACT

BACKGROUND: Severe disease of COVID-19 and mortality occur more frequently in male patients than that in female patients may be related to testosterone level. However, the diagnostic value of changes in the level of testosterone in predicting severe disease of male COVID-19 patients has not been determined yet. METHODS: Sixty-one male COVID-19 patients admitted to the First Affiliated Hospital of Zhejiang University School of Medicine were enrolled. Serum samples at different stages of the patients after admission were collected and testosterone levels were detected to analyze the correlation between testosterone level and disease severity. Transcriptome analysis of PBMC was performed in 34 patients. RESULTS: Testosterone levels at admission in male non-ICU COVID-19 patients (3.7 nmol/L, IQR: 1.5 âˆ¼ 4.7) were significantly lower than those in male ICU COVID-19 patients (6.7 nmol/L, IQR: 4.2 âˆ¼ 8.7). Testosterone levels in the non-ICU group increased gradually during the progression of the disease, while those in the ICU group remained low. In addition, testosterone level of enrolled patients in the second week after onset was significantly correlated with the severity of pneumonia, and ROC curve showed that testosterone level in the second week after onset was highly effective in predicting the severity of COVID-19. Transcriptome studies have found that testosterone levels of COVID-19 patients were associated with immune response, including T cell activation and regulation of lymphocyte activation. In addition, CD28 and Inositol Polyphosphate-4-Phosphatase Type II B (INPP4B) were found positively correlated with testosterone. CONCLUSIONS: Serum testosterone is an independent risk factor for predicting the severity of COVID-19 in male patients, and the level of serum testosterone in the second week after onset is valuable for evaluating the severity of COVID-19. Testosterone level is associated with T cell immune activation. The monitoring of serum testosterone should be highlighted in clinical treatment and the related mechanism should be further studied.


Subject(s)
COVID-19 , Testosterone , Female , Gene Expression Profiling , Humans , Immunity , Leukocytes, Mononuclear , Male , SARS-CoV-2 , Severity of Illness Index , T-Lymphocytes
10.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-293463

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel corona virus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo . Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS-CoV-2 vaccine.

11.
Vaccines (Basel) ; 9(12)2021 Nov 25.
Article in English | MEDLINE | ID: covidwho-1542820

ABSTRACT

The global Coronavirus Disease 2019 (COVID-19) pandemic has accelerated vaccine development at an unprecedented rate. A large population of people have received COVID-19 vaccines, while the vaccine safety data are limited. Here, we reported two cases of herpetic keratitis that occurred soon after receiving the inactivated COVID-19 vaccines. Case 1 was a 60-year-old woman who underwent penetrating keratoplasty (PKP) one year ago for corneal scarring caused by herpes simplex keratitis (HSK), and case 2 was a 51-year-old man with an unremarkable medical history. Both patients developed herpetic keratitis (HSK and varicella-zoster virus corneal endotheliitis, respectively) soon after receiving the inactivated COVID-19 vaccines (Sinovac). Herpetic keratitis was treated successfully with topical or plus oral antiviral ganciclovir. The short latency time in these two cases suggested that an inactivated COVID-19 vaccine may have a risk of triggering ocular herpes virus reactivation. Both clinicians and patients should be aware of this phenomenon. However, a causal relationship awaits confirmation.

12.
Biochem Genet ; 2021 Nov 17.
Article in English | MEDLINE | ID: covidwho-1520387

ABSTRACT

COVID-19 is a serious infectious disease that has recently swept the world, and research on its causative virus, SARS-CoV-2, remains insufficient. Therefore, this study uses bioinformatics analysis techniques to explore the human digestive tract diseases that may be caused by SARS-CoV-2 infection. The gene expression profile data set, numbered GSE149312, is from the Gene Expression Omnibus (GEO) database and is divided into a 24-h group and a 60-h group. R software is used to analyze and screen out differentially expressed genes (DEGs) and then gene ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses are performed. In KEGG, the pathway of non-alcoholic fatty liver disease exists in both the 24-h group and 60-h group. STRING is used to establish a protein-protein interaction (PPI) network, and Cytoscape is then used to visualize the PPI and define the top 12 genes of the node as the hub genes. Through verification, nine statistically significant hub genes are identified: AKT1, TIMP1, NOTCH, CCNA2, RRM2, TTK, BUB1B, KIF20A, and PLK1. In conclusion, the results of this study can provide a certain direction and basis for follow-up studies of SARS-CoV-2 infection of the human digestive tract and provide new insights for the prevention and treatment of diseases caused by SARS-CoV-2.

13.
J Med Libr Assoc ; 109(3): 422-431, 2021 Jul 01.
Article in English | MEDLINE | ID: covidwho-1463960

ABSTRACT

OBJECTIVE: The COVID-19 pandemic highlights the public's need for quality health information that is understandable. This study aimed to identify (1) the extent to which COVID-19 messaging by state public health departments is understandable, actionable, and clear; (2) whether materials produced by public health departments are easily readable; (3) relationships between material type and understandability, actionability, clarity, and reading grade level; and (4) potential strategies to improve public health messaging around COVID-19. METHODS: Based on US Centers for Disease Control and Prevention statistics from June 30, 2020, we identified the ten states with the most COVID-19 cases and selected forty-two materials (i.e., webpages, infographics, and videos) related to COVID-19 prevention according to predefined eligibility criteria. We applied three validated health literacy tools (i.e., Patient Education Materials Assessment Tool, CDC Clear Communication Index, and Flesch-Kincaid Grade Level) to assess material understandability, actionability, clarity, and readability. We also analyzed correlations between scores on the three health literacy tools and material types. RESULTS: Overall, COVID-19 materials had high understandability and actionability but could be improved in terms of clarity and readability. Material type was significantly correlated with understandability, actionability, and clarity. Infographics and videos received higher scores on all tools. CONCLUSIONS: Based on our findings, we recommend public health entities apply a combination of these tools when developing health information materials to improve their understandability, actionability, and clarity. We also recommend using infographics and videos when possible, taking a human-centered approach to information design, and providing multiple modes and platforms for information delivery.


Subject(s)
COVID-19 , Health Education/methods , Health Literacy , Health Promotion/methods , Information Dissemination/methods , Public Health/education , Humans , Pandemics , SARS-CoV-2 , State Government , United States
14.
Front Med (Lausanne) ; 8: 730441, 2021.
Article in English | MEDLINE | ID: covidwho-1450819

ABSTRACT

Objective: A considerable part of COVID-19 patients were found to be re-positive in the SARS-CoV-2 RT-PCR test after discharge. Early prediction of re-positive COVID-19 cases is of critical importance in determining the isolation period and developing clinical protocols. Materials and Methods: Ninety-one patients discharged from Wanzhou Three Gorges Central Hospital, Chongqing, China, from February 10, 2020 to March 3, 2020 were administered nasopharyngeal swab SARS-CoV-2 tests within 12-14 days, and 50 eligible patients (32 male and 18 female) with completed data were enrolled. Average age was 48 ± 11.5 years. All patients underwent non-enhanced chest CT on admission. A total of 568 radiomics features were extracted from the CT images, and 17 clinical factors were collected based on the medical record. Student's t-test and support vector machine-based recursive feature elimination (SVM-RFE) method were used to determine an optimal subset of features for the discriminative model development. Results: After Student's t-test, 62 radiomics features showed significant inter-group differences (p < 0.05) between the re-positive and negative cases, and none of the clinical features showed significant differences. These significant features were further selected by SVM-RFE algorithm, and a more compact feature subset containing only two radiomics features was finally determined, achieving the best predictive performance with the accuracy and area under the curve of 72.6% and 0.773 for the identification of the re-positive case. Conclusion: The proposed radiomics method has preliminarily shown potential in identifying the re-positive cases among the recovered COVID-19 patients after discharge. More strategies are to be integrated into the current pipeline to improve its precision, and a larger database with multi-clinical enrollment is required to extensively verify its performance.

15.
Clin Chim Acta ; 511: 177-180, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1385202

ABSTRACT

To clarify the effect of different respiratory sample types on SARS-CoV-2 detection, we collected throat swabs, nasal swabs and hock-a-loogie saliva or sputum, and compared their detection rates and viral loads. The detection rates of sputum (95.65%, 22/23) and hock-a-loogie saliva (88.09%, 37/42) were significantly higher than those in throat swabs (41.54%, 27/65) and nasal swabs (72.31%, 47/65) (P < 0.001). The Ct Values of sputum, hock-a-loogie saliva and nasal swabs were significantly higher than that in throat swabs, whereas no significant difference was observed between sputum and saliva samples. Hock-a-loogie saliva are reliable sample types that can be used to detect SARS-CoV-2, and worthy of clinical promotion.


Subject(s)
COVID-19/diagnosis , COVID-19/genetics , Polymerase Chain Reaction/standards , SARS-CoV-2/genetics , Saliva/virology , Specimen Handling/standards , Adult , Female , Humans , Male , Middle Aged , Nasopharynx/virology , Polymerase Chain Reaction/methods , Prospective Studies , SARS-CoV-2/isolation & purification , Specimen Handling/methods , Sputum/virology , Viral Load/methods , Viral Load/standards
16.
Medicine (Baltimore) ; 100(34): e26933, 2021 Aug 27.
Article in English | MEDLINE | ID: covidwho-1376350

ABSTRACT

ABSTRACT: It is presently unknown whether imported cases of the 2019 coronavirus disease (COVID-19) have different characteristics when compared with local cases. To compare the clinical characteristics of local cases of COVID-19 in China compared with those imported from abroad.This was a retrospective study of confirmed cases of COVID-19 admitted at the Beijing Ditan Fever Emergency Department between February 29th, 2020, and March 27th, 2020. The clinical characteristics of the patients were compared between local and imported cases.Compared with local cases, the imported cases were younger (27.3 ±â€Š11.7 vs. 43.6 ±â€Š22.2 years, P < .001), had a shorter interval from disease onset to admission (1.0 (0.0-2.0) vs 4.0 (2.0-7.0) days, P < .001), lower frequencies of case contact (17.4% vs 94.1%, P < .001), fever (39.1% vs 82.4%, P < .001), cough (33.3% vs 51.0%, P = .03), dyspnea (1.9% vs 11.8%, P = .01), fatigue (7.5% vs. 27.5%, P = 0.001), muscle ache (4.7% vs. 25.5%, P < 0.001), and comorbidities (P < .05). The imported cases were less severe than the local cases, with 40.4% versus 5.9% mild cases, 2.8% versus 15.7% severe cases, and no critical cases (P < .001). The length of hospital stay was longer in imported cases than in local cases (32.3 ±â€Š14.5 vs 21.7 ±â€Š11.2 days, P < .001). The imported cases showed smaller biochemical perturbations than the local cases. More imported cases had no sign of pneumonia at computed tomography (45.0% vs 14.9%, P = .001), and none had pleural effusion (0% vs 14.9%, P < .001).Compared with local cases, the imported cases of COVID-19 presented with milder disease and less extensive symptoms and signs.


Subject(s)
COVID-19/epidemiology , COVID-19/pathology , Adult , Age Factors , Aged , COVID-19/complications , China/epidemiology , Comorbidity , Female , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Sex Factors , Time-to-Treatment
18.
Acta Pharm Sin B ; 12(4): 1591-1623, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1293568

ABSTRACT

The COVID-19 pandemic caused by the novel SARS-CoV-2 virus has caused havoc across the entire world. Even though several COVID-19 vaccines are currently in distribution worldwide, with others in the pipeline, treatment modalities lag behind. Accordingly, researchers have been working hard to understand the nature of the virus, its mutant strains, and the pathogenesis of the disease in order to uncover possible drug targets and effective therapeutic agents. As the research continues, we now know the genome structure, epidemiological and clinical features, and pathogenic mechanism of SARS-CoV-2. Here, we summarized the potential therapeutic targets involved in the life cycle of the virus. On the basis of these targets, small-molecule prophylactic and therapeutic agents have been or are being developed for prevention and treatment of SARS-CoV-2 infection.

19.
Front Cell Infect Microbiol ; 11: 685640, 2021.
Article in English | MEDLINE | ID: covidwho-1282378

ABSTRACT

Background: Viral nucleic acid detection is considered the gold standard for the diagnosis of coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2 infection. However, unsuitable sample types and laboratory detection kits/methods lead to misdiagnosis, which delays the prevention and control of the pandemic. Methods: We compared four nucleic acid detection methods [two kinds of reverse transcription polymerase chain reactions (RT-PCR A: ORF1ab and N testing; RT-PCRB: only ORF1ab testing), reverse transcription recombinase aided amplification (RT-RAA) and droplet digital RT-PCR (dd-RT-PCR)] using 404 samples of 72 hospitalized COVID-19 patients, including oropharyngeal swab (OPS), nasopharyngeal swabs (NPS) and saliva after deep cough, to evaluate the best sample type and method for SARS-CoV-2 detection. Results: Among the four methods, dd-RT-PCR exhibited the highest positivity rate (93.0%), followed by RT-PCR B (91.2%) and RT-RAA (91.2%), while the positivity rate of RT-PCR A was only 71.9%. The viral load in OPS [24.90 copies/test (IQR 15.58-129.85)] was significantly lower than that in saliva [292.30 copies/test (IQR 20.20-8628.55)] and NPS [274.40 copies/test (IQR 33.10-2836.45)]. In addition, if OPS samples were tested alone by RT-PCR A, only 21.4% of the COVID-19 patients would be considered positive. The accuracy of all methods reached nearly 100% when saliva and NPS samples from the same patient were tested simultaneously. Conclusions: SARS-CoV-2 nucleic acid detection methods should be fully evaluated before use. High-positivity rate methods such as RT-RAA and dd-RT-PCR should be considered when possible. Furthermore, saliva after deep cough and NPS can greatly improve the accuracy of the diagnosis, and testing OPS alone is not recommended.


Subject(s)
COVID-19 Testing/methods , COVID-19 , COVID-19/diagnosis , COVID-19 Nucleic Acid Testing , Humans , Nasopharynx , Pandemics , RNA, Viral/genetics , SARS-CoV-2 , Saliva , Specimen Handling
20.
Signal Transduct Target Ther ; 6(1): 233, 2021 06 11.
Article in English | MEDLINE | ID: covidwho-1265943

ABSTRACT

The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in an unprecedented setback for global economy and health. SARS-CoV-2 has an exceptionally high level of transmissibility and extremely broad tissue tropism. However, the underlying molecular mechanism responsible for sustaining this degree of virulence remains largely unexplored. In this article, we review the current knowledge and crucial information about how SARS-CoV-2 attaches on the surface of host cells through a variety of receptors, such as ACE2, neuropilin-1, AXL, and antibody-FcγR complexes. We further explain how its spike (S) protein undergoes conformational transition from prefusion to postfusion with the help of proteases like furin, TMPRSS2, and cathepsins. We then review the ongoing experimental studies and clinical trials of antibodies, peptides, or small-molecule compounds with anti-SARS-CoV-2 activity, and discuss how these antiviral therapies targeting host-pathogen interaction could potentially suppress viral attachment, reduce the exposure of fusion peptide to curtail membrane fusion and block the formation of six-helix bundle (6-HB) fusion core. Finally, the specter of rapidly emerging SARS-CoV-2 variants deserves a serious review of broad-spectrum drugs or vaccines for long-term prevention and control of COVID-19 in the future.


Subject(s)
COVID-19/metabolism , COVID-19/therapy , Host-Pathogen Interactions , SARS-CoV-2/physiology , Virus Attachment , Virus Internalization , COVID-19/epidemiology , COVID-19/pathology , Humans
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