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1.
Cell Signal ; 109: 110798, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37423342

RESUMO

This study investigated the efficacy of existing vaccines against hospitalization and infection due to the Omicron variant of COVID-19, particularly for those who received two doses of Moderna or Pfizer vaccines and one dose of Johnson & Johnson vaccine or who were vaccinated more than five months before. A total of 36 variants in Omicron's spike protein, targeted by all three vaccinations, have made antibodies less effective at neutralizing the virus. The genotyping of the SARS-CoV-2 viral sequence revealed clinically significant variants such as E484K in three genetic mutations (T95I, D614G, and del142-144). A woman showed two of these mutations, indicating a potential risk of infection after successful immunization, as recently reported by Hacisuleyman (2021). We examine the effects of mutations on domains (NID, RBM, and SD2) found at the interfaces of the spike domains Omicron B.1.1529, Delta/B.1.1529, Alpha/B.1.1.7, VUM B.1.526, B.1.575.2, and B.1.1214 (formerly VOI Iota). We tested the affinity of Omicron for ACE2 and found that the wild- and mutant-spike proteins were using atomistic molecular dynamics simulations. According to the binding free energies calculated during mutagenesis, the ACE2 bound Omicron spikes more strongly than the wild strain SARS-CoV-2. T95I, D614G, and E484K are three substitutions that significantly contribute to RBD, corresponding to ACE2 binding energies and a doubling of the electrostatic potential of Omicron spike proteins. The Omicron appears to bind to ACE2 with greater affinity, increasing its infectivity and transmissibility. The spike virus was designed to strengthen antibody immune evasion through binding while boosting receptor binding by enhancing IgG and IgM antibodies that stimulate human ß-cell, as opposed to the wild strain, which has more vital stimulation of both antibodies.


Assuntos
COVID-19 , Vacinas , Feminino , Humanos , Vacinas contra COVID-19 , COVID-19/prevenção & controle , SARS-CoV-2/genética , Enzima de Conversão de Angiotensina 2 , Infecções Irruptivas , Glicoproteína da Espícula de Coronavírus/genética , Imunoglobulina M
2.
Mol Divers ; 27(2): 695-708, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35616802

RESUMO

SARS, or severe acute respiratory syndrome, is caused by a novel coronavirus (COVID-19). This situation has compelled many pharmaceutical R&D companies and public health research sectors to focus their efforts on developing effective therapeutics. SARS-nCoV-2 was chosen as a protein spike to targeted monoclonal antibodies and therapeutics for prevention and treatment. Deep mutational scanning created a monoclonal antibody to characterize the effects of mutations in a variable antibody fragment based on its expression levels, specificity, stability, and affinity for specific antigenic conserved epitopes to the Spike-S-Receptor Binding Domain (RBD). Improved contacts between Fv light and heavy chains and the targeted antigens of RBD could result in a highly potent neutralizing antibody (NAbs) response as well as cross-protection against other SARS-nCoV-2 strains. It undergoes multipoint core mutations that combine enhancing mutations, resulting in increased binding affinity and significantly increased stability between RBD and antibody. In addition, we improved. Structures of variable fragment (Fv) complexed with the RBD of Spike protein were subjected to our established in-silico antibody-engineering platform to obtain enhanced binding affinity to SARS-nCoV-2 and develop ability profiling. We found that the size and three-dimensional shape of epitopes significantly impacted the activity of antibodies produced against the RBD of Spike protein. Overall, because of the conformational changes between RBD and hACE2, it prevents viral entry. As a result of this in-silico study, the designed antibody can be used as a promising therapeutic strategy to treat COVID-19.


Assuntos
COVID-19 , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , Humanos , Epitopos , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/metabolismo , Internalização do Vírus , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Anticorpos Antivirais/farmacologia , Anticorpos Antivirais/metabolismo , SARS-CoV-2/metabolismo , Ligação Proteica
3.
East Mediterr Health J ; 27(8): 745-754, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34486710

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has rapidly spread to most countries around the world. Disproportionate spread of COVID-19 among the Indian community in Kuwait prompted heightened surveillance in this community. AIMS: To study the epidemiological characteristics of COVID-19 patients and their contacts among the Indian community in Kuwait. METHODS: Data collection was done as a part of contact tracing efforts undertaken by the Kuwaiti Ministry of Health. RESULTS: We analysed contact-tracing data for the initial 1348 laboratory-confirmed Indian patients and 6357 contacts (5681 close and 676 casual). The mean (standard deviation) age of the patients was 39.43 (10.5) years and 76.5% of the cases were asymptomatic or had only mild symptoms. Asymptomatic patients were significantly older [40.05 (10.42) years] than patients with severe symptoms [37.54 (10.54) years] (P = 0.024). About 70% of the patients were living in shared accommodation. Most of the close contacts were living in the same household, as compared with casual contacts, who were primarily workplace contacts (P < 0.001). Among the different occupations, healthcare workers had the highest proportion of cases (18.4%). Among the 216 pairs of cases with a clear relationship between the index and secondary cases, the mean serial interval was estimated to be 3.89 (3.69) days, with a median of 3 and interquartile range of 1-5 days. CONCLUSION: An early increase in the number of COVID-19 cases among the Indian community could be primarily attributed to crowded living conditions and the high proportion of healthcare workers in this community.


Assuntos
COVID-19 , Adulto , COVID-19/etnologia , Busca de Comunicante , Humanos , Índia/etnologia , Kuweit/epidemiologia , Pessoa de Meia-Idade , Pandemias
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