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The Journal of infection ; 2023.
Article in English | EuropePMC | ID: covidwho-2295937
Gene ; 808: 145963, 2022 Jan 15.
Article in English | MEDLINE | ID: covidwho-1415409


As of July 2021, the outbreak of coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has led to more than 200 million infections and more than 4.2 million deaths globally. Complications of severe COVID-19 include acute kidney injury, liver dysfunction, cardiomyopathy, and coagulation dysfunction. Thus, there is an urgent need to identify proteins and genetic factors associated with COVID-19 susceptibility and outcome. We comprehensively reviewed recent findings of host-SARS-CoV-2 interactome analyses. To identify genetic variants associated with COVID-19, we focused on the findings from genome and transcriptome wide association studies (GWAS and TWAS) and bioinformatics analysis. We described established human proteins including ACE2, TMPRSS2, 40S ribosomal subunit, ApoA1, TOM70, HLA-A, and PALS1 interacting with SARS-CoV-2 based on cryo-electron microscopy results. Furthermore, we described approximately 1000 human proteins showing evidence of interaction with SARS-CoV-2 and highlighted host cellular processes such as innate immune pathways affected by infection. We summarized the evidence on more than 20 identified candidate genes in COVID-19 severity. Predicted deleterious and disruptive genetic variants with possible effects on COVID-19 infectivity have been also summarized. These findings provide novel insights into SARS-CoV-2 biology and infection as well as potential strategies for development of novel COVID therapeutic targets and drug repurposing.

COVID-19/metabolism , Host Microbial Interactions/genetics , SARS-CoV-2/metabolism , COVID-19/physiopathology , Computational Biology/methods , Cryoelectron Microscopy/methods , Crystallography, X-Ray/methods , Genome-Wide Association Study , Host Microbial Interactions/physiology , Host-Pathogen Interactions/genetics , Humans , Proteins/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity
Front Med (Lausanne) ; 8: 667623, 2021.
Article in English | MEDLINE | ID: covidwho-1337648


Background: The Coronavirus disease 2019 (COVID-19) pandemic has been a major threat to global health. Regional differences in epidemiological and clinical characteristics, treatment and outcomes of patients have not yet been investigated. This study was conducted to investigate these differences amongCOVID-19 patients in Hubei Province, China. Methods: This retrospective cross-sectional study analyzed data on 289 COVID-19 patients from designated hospitals in three regions:Urban (Wuhan Union West Hospital), Suburban areas of Wuhan (Hannan Hospital) and Enshi city, between February 8 and 20, 2020. The final date of follow-up was December 14th, 2020. The outcomes were case fatality rate and epidemiological and clinical data. Results: Urban Wuhan experienced a significantly higher case fatality rate (21.5%) than suburban Wuhan (5.23%) and rural area of Enshi (3.51%). Urban Wuhan had a higher proportion of patients on mechanical ventilation (24.05%) than suburban Wuhan (0%) and rural Enshi (3.57%). Treatment with glucocorticoids was equivalent in urban and suburban Wuhan (46.84 and 45.75%, respectively) and higher than Enshi (25.00%). Urban Wuhan had a higher proportion of patients with abnormal tests including liver function and serum electrolytes and a higher rate of pneumonia (p < 0.01 for all). Urban Wuhan also had a higher incidence of respiratory failure, heart disease, liver disease and shock, compared with the other two regions (all p < 0.05). Conclusions: Our findings revealed that there are regional differences in COVID-19. These findings provide novel insights into the distribution of appropriate resources for the prevention, control and treatment of COVID-19 for the global community.

J Transl Med ; 18(1): 321, 2020 08 24.
Article in English | MEDLINE | ID: covidwho-727282


BACKGROUND: The outbreak of coronavirus disease (COVID-19) was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), through its surface spike glycoprotein (S-protein) recognition on the receptor Angiotensin-converting enzyme 2 (ACE2) in humans. However, it remains unclear how genetic variations in ACE2 may affect its function and structure, and consequently alter the recognition by SARS-CoV-2. METHODS: We have systemically characterized missense variants in the gene ACE2 using data from the Genome Aggregation Database (gnomAD; N = 141,456). To investigate the putative deleterious role of missense variants, six existing functional prediction tools were applied to evaluate their impact. We further analyzed the structural flexibility of ACE2 and its protein-protein interface with the S-protein of SARS-CoV-2 using our developed Legion Interfaces Analysis (LiAn) program. RESULTS: Here, we characterized a total of 12 ACE2 putative deleterious missense variants. Of those 12 variants, we further showed that p.His378Arg could directly weaken the binding of catalytic metal atom to decrease ACE2 activity and p.Ser19Pro could distort the most important helix to the S-protein. Another seven missense variants may affect secondary structures (i.e. p.Gly211Arg; p.Asp206Gly; p.Arg219Cys; p.Arg219His, p.Lys341Arg, p.Ile468Val, and p.Ser547Cys), whereas p.Ile468Val with AF = 0.01 is only present in Asian. CONCLUSIONS: We provide strong evidence of putative deleterious missense variants in ACE2 that are present in specific populations, which could disrupt the function and structure of ACE2. These findings provide novel insight into the genetic variation in ACE2 which may affect the SARS-CoV-2 recognition and infection, and COVID-19 susceptibility and treatment.

Betacoronavirus/physiology , Mutation, Missense , Peptidyl-Dipeptidase A/genetics , Protein Interaction Domains and Motifs/genetics , Spike Glycoprotein, Coronavirus/metabolism , Amino Acid Substitution , Angiotensin-Converting Enzyme 2 , Betacoronavirus/metabolism , Binding Sites/genetics , COVID-19 , Coronavirus Infections/ethnology , Coronavirus Infections/genetics , Coronavirus Infections/virology , DNA Mutational Analysis/methods , Databases, Genetic , Genetic Predisposition to Disease/ethnology , Genetic Variation , Geography , Humans , Models, Molecular , Molecular Docking Simulation , Pandemics , Peptidyl-Dipeptidase A/chemistry , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/ethnology , Pneumonia, Viral/genetics , Pneumonia, Viral/virology , Polymorphism, Single Nucleotide , Protein Binding , Protein Structure, Secondary/genetics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry , Virus Internalization