Impact of African-Specific ACE2 Polymorphisms on Omicron BA.4/5 RBD Binding and Allosteric Communication Within the ACE2–RBD Protein Complex

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 1367 - 1367

Опубликована: Фев. 6, 2025

Severe acute respiratory symptom coronavirus 2 (SARS-CoV-2) infection occurs via the attachment of spike (S) protein’s receptor binding domain (RBD) to human ACE2 (hACE2). Natural polymorphisms in hACE2, particularly at interface, may alter RBD–hACE2 interactions, potentially affecting viral infectivity across populations. This study identified effects six naturally occurring hACE2 with high allele frequency African population (S19P, K26R, M82I, K341R, N546D and D597Q) on interaction S protein RBD BA.4/5 Omicron sub-lineage through post-molecular dynamics (MD), inter-protein dynamic residue network (DRN) analyses. Inter-protein analysis suggested that K26R variation, highest aligns reports enhanced increased SARS-CoV-2 susceptibility. Conversely, S19P, showing fewest interactions largest distances, agrees studies indicating it hinders binding. The M82I substitution destabilized reducing contact from 92 (WT) 27. K341R variant, located distally, had allosteric contacts compared WThACE2. polymorphism has been linked affinity for Alpha, Beta Delta lineages. DRN analyses revealed networks, especially key residues involved enzyme activity Notably, S19P weaken hACE2–RBD while showed reduced centrality zinc chloride-coordinating residues, hinting impaired communication pathways. Overall, our findings show affect stability modulate influencing infectivity—key insights vaccine therapeutic development.

Язык: Английский

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Polymorphisms and mutations of ACE2 and TMPRSS2 genes are associated with COVID-19: a systematic review

European journal of medical research, Год журнала: 2022, Номер 27(1)

Опубликована: Фев. 22, 2022

To determine the effect of polymorphisms and mutations in angiotensin-converting enzyme 2 (ACE2) Type transmembrane serine proteases (TMPRSS2) genes on susceptibility to corona virus disease 2019 (COVID-19) patient prognosis.From December current time, an outbreak epidemic COVID-19, characterized by severe acute respiratory syndrome coronavirus (SARS-CoV-2) has occurred around world. It is now clear that SARS-CoV-2 binds human ACE2 receptors, with expression these receptors correlated rate infection mortality. Polymorphisms individual factors, such as TMPRSS2 have been linked increase negative outcomes, although evidence affirm remains debatable.Here, we performed a systematic review, based guidelines Preferred Reporting Items for Systematic Reviews Meta-Analyses (PRISMA) criteria, aim assessing whether affect COVID-19 condition. We extensively searched PubMed, MEDLINE, Embase, Cochrane Library, Web Science databases, relevant articles reports published English between 2021.A total 495 full-text were downloaded, which 185 excluded after preliminary examination they duplicates. Finally, 310 evaluated, reading their titles abstracts, 208 them eliminated our selection criteria. 33 met inclusion criteria included final assessment. Genetic data from 33,923 patients drawn general population deriving over 160 regions 50 countries, well approximately 560,000 samples global-public genetic analysis. Ultimately, identified 10 SNPs 21 gene, along 13 12 variants may be associated COVID-19.ACE2 play vital roles onset, development, prognosis infection, both strongly vulnerability, intensity, clinical result COVID-19. Overall, factors potential future development personalized drugs vaccines against COVID-19.CRD42021239400 PROSPERO 2021.

Язык: Английский

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Impacts of exposure to air pollution, radon and climate drivers on the COVID-19 pandemic in Bucharest, Romania: A time series study

Environmental Research, Год журнала: 2022, Номер 212, С. 113437 - 113437

Опубликована: Май 18, 2022

During the ongoing global COVID-19 pandemic disease, like several countries, Romania experienced a multiwaves pattern over more than two years. The spreading of SARS-CoV-2 pathogens in Bucharest, capital is multi-factorial process involving among other factors outdoor environmental variables and viral inactivation. Through descriptive statistics cross-correlation analysis applied to daily time series observational geospatial data, this study aims evaluate synergy incidence lethality with air pollution radon under different climate conditions, which may exacerbate coronavirus' effect on human health. entire analyzed period 1 January 2020-21 December 2021, for each four waves were recorded anomalous anticyclonic synoptic meteorological patterns mid-troposphere, favorable stability conditions during fall-early winter seasons disease fast-spreading, mostly second, fourth waves. As temporal airborne its mutagen variants affected by seasonal variability main pollutants parameters, paper found: 1) exposures (particulate matter PM2.5 PM10, nitrogen dioxide-NO2, sulfur dioxide-SO2, carbon monoxide-CO) - 222Rn, are directly correlated mortality, contribute spread severity pandemic; 2) ground ozone-O3 levels, temperature, Planetary Boundary Layer height, surface solar irradiance anticorrelated new deaths, averageingful spring-summer periods. Outdoor exposure ambient associated non-negligible driver transmission large metropolitan areas, risk infection. findings provide useful information public health authorities decision-makers develop future diseases strategies high polluted environments.

Язык: Английский

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Assessing the impact of air pollution and climate seasonality on COVID-19 multiwaves in Madrid, Spain

Environmental Research, Год журнала: 2021, Номер 203, С. 111849 - 111849

Опубликована: Авг. 6, 2021

While the COVID-19 pandemic is still in progress, being under fifth wave Madrid, over more than one year, Spain experienced a four pattern. The transmission of SARS-CoV-2 pathogens Madrid metropolitan region was investigated from an urban context associated with seasonal variability climate and air pollution drivers. Based on descriptive statistics regression methods in-situ geospatial daily time series data, this study provides comparative analysis between waves incidence mortality cases different quality conditions. During analyzed period 1 January 2020-1 July 2021, for each were recorded anomalous anticyclonic synoptic meteorological patterns mid-troposphere favorable stability conditions disease fast spreading. As airborne microbial temporal pattern most affected by changes, paper found: 1) significant negative correlation temperature, Planetary Boundary Layer height, surface solar irradiance new deaths; 2) similar mutual seasonality variables first fourth COVID-waves spring seasons 2020 2021 years. Such information may help health decision makers public plan future.

Язык: Английский

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Molecular definition of severe acute respiratory syndrome coronavirus 2 receptor‐binding domain mutations: Receptor affinity versus neutralization of receptor interaction

Allergy, Год журнала: 2021, Номер 77(1), С. 143 - 149

Опубликована: Июль 9, 2021

Abstract Background Several new variants of SARS‐CoV‐2 have emerged since fall 2020 which multiple mutations in the receptor‐binding domain (RBD) spike protein. It is unclear affect receptor affinity versus immune recognition. Methods We produced wild type RBD, RBD with single (E484K, K417N, or N501Y) all three combined and tested their binding to ACE2 by biolayer interferometry (BLI). The ability convalescent sera recognize RBDs block interaction was as well. Results demonstrated that mutation N501Y increased but did not strongly its recognition sera. In contrast, E484K had almost no impact on kinetics, essentially abolished Interestingly, combining E484K, resulted a both features: enhanced Conclusions Our data demonstrate either while triple mutant combine features.

Язык: Английский

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Long COVID: Molecular Mechanisms and Detection Techniques

International Journal of Molecular Sciences, Год журнала: 2023, Номер 25(1), С. 408 - 408

Опубликована: Дек. 28, 2023

Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), has emerged a significant health concern following the COVID-19 pandemic. Molecular mechanisms underlying occurrence and progression long COVID include viral persistence, immune dysregulation, endothelial dysfunction, neurological involvement, highlight need for further research to develop targeted therapies this condition. While clearer picture clinical symptomatology is shaping, many molecular are yet be unraveled, given their complexity high level interaction with other metabolic pathways. This review summarizes some most important symptoms associated that occur in well relevant techniques can used understanding pathogen, its affinity towards host, possible outcomes host-pathogen interaction.

Язык: Английский

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Genomic Variation and Diversification in Begomovirus Genome in Implication to Host and Vector Adaptation

Plants, Год журнала: 2021, Номер 10(8), С. 1706 - 1706

Опубликована: Авг. 19, 2021

Begomoviruses (family Geminiviridae, genus Begomovirus) are DNA viruses transmitted in a circulative, persistent manner by the whitefly Bemisia tabaci (Gennadius). As revealed their wide host range (more than 420 plant species), worldwide distribution, and effective vector transmission, begomoviruses highly adaptive. Still, genetic factors that facilitate adaptation to diverse array of hosts vectors remain poorly understood. Mutations virus genome may confer selective advantage for essential functions, such as replication, evading responses, movement within host. Therefore, variation is vital evolution and, response selection pressure, demonstrated emergence new strains species adapted or with unique pathogenicity. The combination forms imprint on genome. This review focuses contribute Begomovirus global spread, which an unforeseen diversity dispersal has been recognized continues expand.

Язык: Английский

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The Impact of ACE and ACE2 Gene Polymorphisms in Pulmonary Diseases Including COVID-19

In Vivo, Год журнала: 2021, Номер 36(1), С. 13 - 29

Опубликована: Дек. 30, 2021

Chronic and acute respiratory diseases pose a major problem for public health worldwide due to the high morbidity mortality rates, while treatment options remain mostly symptomatic. The renin-angiotensin system (RAS) plays an important role in lung tissue, regulating pulmonary circulation blood pressure, but also contributing normal function development. Angiotensin-converting enzyme (ACE) its homologous angiotensin-converting 2 (ACE2) are considered be amongst main RAS regulators highly expressed vascular endothelium. This review discusses impact of ACE ACE2 functional gene polymorphisms on seven diseases, terms predisposition, course, outcome, revealing their potential utility as both genetic markers biomarkers. discussed conditions include chronic obstructive disease (COPD), hypertension (PH), asthma, injury (ALI), distress syndrome (ARDS), cancer sarcoidosis (PS), well SARS-CoV-2 viral infection COVID-19 disease.

Язык: Английский

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Pharmacogenetics and Precision Medicine Approaches for the Improvement of COVID-19 Therapies

Frontiers in Pharmacology, Год журнала: 2022, Номер 13

Опубликована: Фев. 18, 2022

Many drugs are being administered to tackle coronavirus disease 2019 (COVID-19) pandemic situations without establishing clinical effectiveness or tailoring safety. A repurposing strategy might be more effective and successful if pharmacogenetic interventions considered in future studies/trials. Although it is very unlikely that there almost no data for COVID-19 drugs, however, from inferring the pharmacokinetic (PK)/pharmacodynamic(PD) properties some evidence other diseases/clinical conditions, highly likely associations also feasible at least drugs. We strongly mandate undertake a assessment these drug–gene pairs (atazanavir– UGT1A1 , ABCB1 SLCO1B1 APOA5 ; efavirenz– CYP2B6 nevirapine– HLA lopinavir– SLCO1B3 ABCC2 ribavirin– SLC28A2 tocilizumab– FCGR3A ivermectin– oseltamivir– CES1 clopidogrel– CYP2C19 warfarin– CYP2C9 VKORC1 non-steroidal anti-inflammatory (NSAIDs)– ) patients advancing precision medicine. Molecular docking computational studies promising achieve new therapeutics against SARS-CoV-2 infection. The current situation discovery of anti-SARS-CoV-2 agents four important targets silico has been described summarized this review. natural occurring compounds different herbs infection favorable, accurate experimental investigation warranted provide insightful information. Moreover, considerations drug–drug interactions (DDIs) drug–herb (DHIs) existing repurposed along with (e.g., efavirenz herbogenetic andrographolide interventions, collectively called multifactorial (DGIs), may further accelerate development therapies real-world settings.

Язык: Английский

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Immunopathogenesis and Immunogenetic Variants in COVID-19

Current Pharmaceutical Design, Год журнала: 2022, Номер 28(22), С. 1780 - 1797

Опубликована: Май 22, 2022

Coronavirus disease 2019 (COVID-19) continues to spread globally despite the discovery of vaccines. Many people die due COVID-19 as a result catastrophic consequences, such acute respiratory distress syndrome, pulmonary embolism, and disseminated intravascular coagulation caused by cytokine storm. Immunopathology immunogenetic research may assist in diagnosing, predicting, treating severe storm associated with COVID-19. This paper reviews immunopathogenesis variants that play role Although various immune-related genetic have been investigated relation COVID-19, NOD-like receptor protein 3 (NLRP3) interleukin 18 (IL-18) not assessed for their potential significance clinical outcome. Here, we a) summarize current understanding etiology pathophysiology storm; b) construct analyze protein-protein interaction (PPI) networks (using enrichment annotation analysis) based on NLRP3 IL18 all genes, which were established Our PPI network analyses predict useful drug targets prevent onset including key antiviral pathways Toll-Like-Receptor cascades, signaling, RIG-induction interferon (IFN) α/β, (IL)-1, IL-6, IL-12, IL-18, tumor necrosis factor signaling; SARS-CoV-2 innate immune evasion participation MYD88 MAVS The be used more outcomes, thereby opening door targeted preventive treatments.

Язык: Английский

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