Journal of Applied Genetics, Journal Year: 2022, Volume and Issue: 63(2), P. 423 - 428
Published: March 12, 2022
Language: Английский
Molecular Cancer, Journal Year: 2021, Volume and Issue: 20(1)
Published: Feb. 16, 2021
Abstract mRNA vaccines have tremendous potential to fight against cancer and viral diseases due superiorities in safety, efficacy industrial production. In recent decades, we witnessed the development of different kinds mRNAs by sequence optimization overcome disadvantage excessive immunogenicity, instability inefficiency. Based on immunological study, are coupled with immunologic adjuvant various delivery strategies. Except for optimization, assistance mRNA-delivering strategies is another method stabilize improve their efficacy. The understanding increasing antigen reactiveness gains insight into mRNA-induced innate immunity adaptive without antibody-dependent enhancement activity. Therefore, address problem, scientists further exploited carrier-based (lipid-based delivery, polymer-based peptide-based virus-like replicon particle cationic nanoemulsion), naked dendritic cells-based vaccines. article will discuss molecular biology underlying anti-virus anti-tumor mechanisms, an introduction phenomena, strategies, importance Corona Virus Disease 2019 (COVID-19) related clinical trials diseases. Finally, challenge bacterial parasitic
Language: Английский
Citations
308
Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)
Published: Nov. 25, 2020
Abstract COVID-19 is caused by the coronavirus SARS-CoV-2, which jumped into human population in late 2019 from a currently uncharacterised animal reservoir. Due to this recent association with humans, SARS-CoV-2 may not yet be fully adapted its host. This has led speculations that evolving towards higher transmissibility. The most plausible mutations under putative natural selection are those have emerged repeatedly and independently (homoplasies). Here, we formally test whether any homoplasies observed date significantly associated increased viral transmission. To do so, develop phylogenetic index quantify relative number of descendants sister clades without specific allele. We apply curated set recurrent identified within dataset 46,723 genomes isolated patients worldwide. identify single mutation convincingly Instead, circulation appear evolutionary neutral primarily induced immune system via RNA editing, rather than being signatures adaptation. At stage find no evidence for more transmissible lineages due mutations.
Language: Английский
Citations
306
Genomics, Journal Year: 2020, Volume and Issue: 113(1), P. 1221 - 1232
Published: Sept. 30, 2020
Language: Английский
Citations
167
Genome Biology and Evolution, Journal Year: 2021, Volume and Issue: 13(5)
Published: April 22, 2021
The COVID-19 pandemic has seen an unprecedented response from the sequencing community. Leveraging sequence data more than 140,000 SARS-CoV-2 genomes, we study mutation rates and selective pressures affecting virus. Understanding processes effects of selection profound implications for viral evolution, vaccine design, tracking spread. We highlight address some common genome analysis pitfalls that can lead to inaccurate inference selection, such as ignoring skews in genetic code, not accounting recurrent mutations, assuming evolutionary equilibrium. find two particular rates, G →U C →U, are similarly elevated considerably higher all other causing majority mutations genome, possibly result APOBEC ROS activity. These also tend occur many times at same positions along global phylogeny (i.e., they very homoplasic). observe effect genomic context on but is overall limited. Although previous studies have suggested acting decrease U content synonymous sites, bring forward evidence suggesting opposite.
Language: Английский
Citations
120
Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 23(9), P. 547 - 562
Published: April 22, 2022
Language: Английский
Citations
120
Seminars in Immunology, Journal Year: 2021, Volume and Issue: 55, P. 101533 - 101533
Published: June 1, 2021
Responsible for more than 4.9 million deaths so far, COVID-19, caused by SARS-CoV-2, is instigating devastating effects on the global health care system whose impacts could be longer years to come. Acquiring a comprehensive knowledge of host-virus interaction critical designing effective vaccines and/or drugs. Understanding evolution virus and impact genetic variability host immune evasion vaccine efficacy helpful design novel strategies minimize emerging variants concern (VOC). Most under development in current use target spike protein owning its unique function receptor binding, relatively conserved nature, potent immunogenicity inducing neutralizing antibodies, being good T cell responses. However, SARS-CoV-2 strains are exhibiting which affect antibody-based therapies addition enhancing viral mechanisms. Currently, degree mutations immunity vaccination, ability confer protection against attracts much attention. This review discusses implications vaccine-induced forward directions contribute future studies focusing immunotherapies consider evolution. Combining derived from different regions that boost both humoral cellular wings adaptive best options cope with VOC.
Language: Английский
Citations
106
Vaccines, Journal Year: 2023, Volume and Issue: 11(8), P. 1304 - 1304
Published: July 31, 2023
Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is a prevalent global infectious disease and leading cause of mortality worldwide. Currently, the only available vaccine for TB prevention Bacillus Calmette-Guérin (BCG). However, BCG demonstrates limited efficacy, particularly in adults. Efforts to develop effective vaccines have been ongoing nearly century. In this review, we examined current obstacles research emphasized significance understanding interaction mechanism between MTB hosts order provide new avenues establish solid foundation development novel vaccines. We also assessed various candidates, including inactivated vaccines, attenuated live subunit viral vector DNA emerging mRNA as well virus-like particle (VLP)-based which are currently preclinical stages or clinical trials. Furthermore, discussed challenges opportunities associated with developing different types outlined future directions research, aiming expedite This comprehensive review offers summary progress made field
Language: Английский
Citations
58
Cellular and Molecular Immunology, Journal Year: 2023, Volume and Issue: 21(2), P. 171 - 183
Published: Nov. 20, 2023
Abstract An ancient conflict between hosts and pathogens has driven the innate adaptive arms of immunity. Knowledge about this interplay can not only help us identify biological mechanisms but also reveal pathogen vulnerabilities that be leveraged therapeutically. The humoral response to SARS-CoV-2 infection been focus intense research, role immune system received significantly less attention. Here, we review current knowledge various means employs evade defense systems. We consider immunity in vaccines phenomenon long COVID.
Language: Английский
Citations
51
Biochemical and Biophysical Research Communications, Journal Year: 2020, Volume and Issue: 538, P. 35 - 39
Published: Nov. 5, 2020
The extensive sequence data generated from SARS-CoV-2 during the 2020 pandemic has facilitated study of viral genome evolution over a brief period time. This highlighted instances directional mutation pressures exerted on host antiviral defense systems. In this review we describe three such human mechanisms, apolipoprotein B mRNA editing catalytic polypeptide-like proteins (APOBEC), adenosine deaminase acting RNA (ADAR), and reactive oxygen species (ROS), discuss their potential implications evolution.
Language: Английский
Citations
100
Journal of Chemical Information and Modeling, Journal Year: 2020, Volume and Issue: 60(10), P. 5080 - 5102
Published: Aug. 27, 2020
A new coronavirus (SARS-CoV-2) is a global threat to world health and economy. Its dimeric main protease (Mpro), which required for the proteolytic cleavage of viral precursor proteins, good candidate drug development owing its conservation absence human homolog. Improving our understanding Mpro behavior can accelerate discovery effective therapies reduce mortality. All-atom molecular dynamics (MD) simulations (100 ns) 50 mutant dimers obtained from filtered sequences GISAID database were analyzed using root-mean-square deviation, fluctuation, Rg, averaged betweenness centrality, geometry calculations. The results showed that SARS-CoV-2 essentially behaves in similar manner SAR-CoV However, we report following findings variants: (1) Residues GLY15, VAL157, PRO184 have mutated more than once SARS CoV-2; (2) D48E variant has lead novel "TSEEMLN"" loop at binding pocket; (3) inactive apo does not show signs dissociation 100 ns MD; (4) non-canonical pose PHE140 widens substrate surface; (5) dual allosteric pockets coinciding with various stabilizing functional components pocket found display correlated compaction dynamics; (6) high centrality values residues 17 128 all samples suggest their importance dimer stability-one such consequence been observed M17I mutation whereby one N-fingers was highly unstable. (7) Independent coarse-grained Monte Carlo relationship between rigidity/mutability enzymatic function. Our entire approach combining preparation, retrieval, homology modeling, dynamic residue network (DRN), relevant conformation retrieval 1-D kernel density estimates reaction coordinates other existing approaches structural analysis, data visualization within coronaviral also applicable proteins.
Language: Английский
Citations
85