Endocrine, Journal Year: 2024, Volume and Issue: 85(3), P. 1435 - 1445
Published: June 1, 2024
Language: Английский
Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)
Published: Jan. 27, 2023
After over two years of living with Covid-19 and hundreds million cases worldwide there is still an unmet need to find proper treatments for the novel coronavirus, due also rapid mutation its genome. In this context, a drug repositioning study has been performed, using in silico tools targeting Delta Spike protein/ACE2 interface. To aim, it virtually screened library composed by 4388 approved drugs through deep learning-based QSAR model identify protein-protein interactions modulators molecular docking against receptor binding domain (RBD). Binding energies predicted complexes were calculated Molecular Mechanics/Generalized Born Surface Area from dynamics simulations. Four out top twenty ranking compounds showed stable modes on RBD evaluated their effectiveness Omicron. Among them antihistaminic drug, fexofenadine, revealed very low energy, complex, interesting RBD. Several found exhibit direct antiviral activity SARS-CoV-2 vitro, mechanisms action debated. This not only highlights potential our computational methodology screening variant-specific drugs, but represents further tool investigating properties selected drugs.
Language: Английский
Citations
39
Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)
Published: March 31, 2023
Abstract Viral and host factors can shape SARS-CoV-2 evolution. However, little is known about lineage-specific vaccination-specific mutations that occur within individuals. Here, we analysed deep sequencing data from 2,820 respiratory samples with different viral lineages to describe the patterns of within-host diversity under conditions, including vaccine-breakthrough infections. In unvaccinated individuals, variant Concern (VOC) Alpha, Delta, Omicron were found have higher neutral purifying selection at full genome level compared non-VOC SARS-CoV-2. Breakthrough infections in 2-dose or 3-dose Comirnaty CoronaVac vaccinated individuals did not increase levels non-synonymous change direction pressure. Vaccine-induced antibody T cell responses appear significant impact on sequence diversification. Our findings suggest vaccination does exploration protein space may facilitate emergence variants.
Language: Английский
Citations
28
The Journal of Physical Chemistry B, Journal Year: 2022, Volume and Issue: 126(36), P. 6835 - 6852
Published: Sept. 6, 2022
Electrostatic intermolecular interactions are important in many aspects of biology. We have studied the main electrostatic features involved interaction receptor-binding domain (RBD) SARS-CoV-2 spike protein with human receptor Angiotensin-converting enzyme 2 (ACE2). As principal computational tool, we used FORTE approach, capable to model proton fluctuations and computing free energies for a very large number protein–protein systems under different physical–chemical conditions, here focusing on RBD-ACE2 interactions. Both wild-type all critical variants included this study. From our ensemble extensive simulations, obtain, as function pH, binding affinities, charges proteins, their charge regulation capacities, dipole moments. In addition, calculated pKas ionizable residues mapped coupling between them. able present simple predictor based data obtained Alpha, Beta, Gamma, Delta, Omicron variants, linear correlation total RBD corresponding affinity. This "RBD rule" should work quick test degree severity coming future.
Language: Английский
Citations
31
Virology Journal, Journal Year: 2024, Volume and Issue: 21(1)
Published: April 26, 2024
About four years have passed since the detection of first cases COVID-19 in China. During this lethal pandemic, millions people lost their lives around world. Since waves infection, various pharmacotherapeutic agents been examined management COVID-19. Despite all these efforts pharmacotherapy, drug repurposing, and design development new drugs, multiple organ involvement complications occurred during Some became chronic long-lasting which led to "long COVID" syndrome appearance. Therefore, best way eradicate pandemic is prophylaxis through mass vaccination. In regard, vaccine platforms including inactivated vaccines, nucleic acid-based vaccines (mRNA DNA vaccines), adenovirus-vectored protein-based subunit designed developed prevent or reduce hospitalization, mortality rates. focused review, at first, most commonly reported clinical presentations summarized. addition, different therapeutic regimens latest status listed. Furthermore, related signs, symptoms, mentioned. At end, effectiveness available with against early SARS-CoV-2 variants currently circulating interest (VOI) necessity booster shots summarized discussed more detail.
Language: Английский
Citations
6
Informatics in Medicine Unlocked, Journal Year: 2023, Volume and Issue: 39, P. 101256 - 101256
Published: Jan. 1, 2023
Numerous variations of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), including D614G, B.1.1.7 (United Kingdom), B.1.1.28 (Brazil P1, P2), CAL.20C (Southern California), B.1.351 (South Africa), B.1.617 (B.1.617.1 Kappa & Delta B.1.617.2) and B.1.1.529, have been reported worldwide. The receptor-binding domain (RBD) spike (S) protein is involved in virus-cell binding, where virus-neutralizing antibodies (NAbs) react. Novel variants S-protein could maximize viral affinity for human angiotensin-converting enzyme 2 (ACE2) receptor increase virus transmission. Molecular detection with false-negative results may refer to mutations part virus's genome used diagnosis. Furthermore, these changes structure alter neutralizing ability NAbs, resulting a reduction vaccine efficiency. Further information needed evaluate how new affect efficacy.
Language: Английский
Citations
14
Vaccines, Journal Year: 2022, Volume and Issue: 10(7), P. 1068 - 1068
Published: July 3, 2022
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome 2 (SARS-CoV-2), is associated with a robust immune response. development of systemic inflammation leads to hyperinflammatory state due cytokine release during COVID-19. emergence many new SARS-CoV-2 variants across the world deteriorates protective antiviral immunity induced after infection or vaccination. innate response crucial for determining fate COVID-19 symptomatology. T cell-mediated main factor response; moreover, initiates rapid B-cell In this paper, we present current knowledge on and We discuss mechanisms various types vaccines (nucleoside-modified, adenovirus-vectored, inactivated virus recombinant protein adjuvanted formulations). This includes specific aspects vaccination in selected patient populations altered activity (the elderly, children, pregnant women, solid organ transplant recipients, patients rheumatic diseases malignancies). also diagnostic research tools available study anti-SARS-CoV-2 cellular humoral responses.
Language: Английский
Citations
22
Viruses, Journal Year: 2023, Volume and Issue: 15(2), P. 446 - 446
Published: Feb. 5, 2023
The association between nasopharyngeal (NP) SARS-CoV-2 viral loads and clinical outcomes remains debated. Here, we examined the factors that might predict NP load role of as a predictor outcomes. A convenience sample 955 positive remnant swab eluent samples collected during routine care 18 November 2020 26 September 2021 was cataloged chart review performed. For non-duplicate with available demographic data (i.e., non-employees), an aliquot sent for droplet digital PCR quantification load. Univariate multivariate analyses were performed to identify predictors COVID-19-related Samples from 698 individuals included in final analysis. cohort had mean age 50 years (range: 19–91); 86.6% male 76.3% unvaccinated. higher people respiratory symptoms (p = 0.0004) fevers 0.0006). In predictive models outcomes, approached significance in-hospital mortality. conclusion, did not appear be strong moderate-to-severe disease pre-Delta Delta phases pandemic, but symptomatic diseases mortality, providing support thesis early control prevents progression disease.
Language: Английский
Citations
12
Vaccine, Journal Year: 2024, Volume and Issue: 42(21), P. 126153 - 126153
Published: Aug. 1, 2024
Language: Английский
Citations
4
Complex Issues of Cardiovascular Diseases, Journal Year: 2025, Volume and Issue: 13(4), P. 62 - 76
Published: Jan. 11, 2025
Highlights The article presents the results of analysis age and gender characteristics patients, epidemiological clinical features course new coronavirus infection, appropriate patient care strategies in Kemerovo region – Kuzbass 2020–2022 according to Federal Registry COVID-19 patients. Annotation Aim . To analyze infection (NCI, COVID-19), aspects for this cohort patients using data from Methods object study was (for Kuzbass). presented format as January 10, 2023 dynamics June 14, 2020 December 31, 2022. subject retrospective included: prevalence morbidity associated with COVID-19, mortality NCI, type medical care/treatment its absence (outpatient, inpatient, including treatment intensive unit (ICU)), severity NCI (mild, moderate, severe, extremely severe), etc. adult population (18 years older) permanently residing included U07.1 U07.2 ICD-10-CM codes. Results authors analyzed 345,588 diagnosed NCI. median 53.2 (38.7; 66.0) years. majority participants were female (61%), number males much lower (39%). disease 2,593.1 cases per 100 thousand Kuzbass, 2021 it 6,764.5 cases, 2022 7,468.8 group. people mild (78.3%) less often moderate (16.8%) disease. noted that severe (2.9%) (2.0%) detected same frequency. undergoing outpatient (75.9%), a quarter (23.7%) inpatient treatment, 0.4% refused treatment. duration 11 (7.0; 15.0) days, lasted 10.0 14.0) bed-days. inpatients 16.7 older than outpatients. In ICU, 7,025 received during period, which accounted 2% all aged≥ 18 8.6% those who hospitalized. 75.1% treated ICU needed mechanical ventilation. During 3.9% died. Mortality amounted 124.6 population, 392.5 136 cases. deceased persons 72 (64.4; 81.8) years, women 3.6 men. Conclusion made possible systematize on well 2020-2022 obtained can be used rational allocation healthcare resources.
Language: Английский
Citations
0
Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12
Published: Oct. 10, 2022
COVID-19 infection caused by SARS-CoV-2 is considered catastrophic because it affects multiple organs, particularly those of the respiratory tract. Although consequences this are not fully clear, causes damage to lungs, cardiovascular and nervous systems, other subsequently inducing organ failure. In particular, effects SARS-CoV-2-induced inflammation on cancer cells tumor microenvironment need be investigated. may alter microenvironment, promoting cell proliferation dormant (DCC) reawakening. DCCs reawakened upon with can populate premetastatic niche in lungs leading dissemination. DCC reawakening consequent neutrophil monocyte/macrophage activation an uncontrolled cascade pro-inflammatory cytokines most severe clinical COVID-19. Moreover, extracellular traps have been demonstrated activate dissemination into lungs. Further studies warranted better define roles as well development metastasis; results these will aid further targeted therapies, both for prevention treatment patients
Language: Английский
Citations
16