Potential Innovations in Modern-Day Human and Animal Vaccine Development DOI Open Access
Theodor-Nicolae Carp

Опубликована: Июль 26, 2024

The vaccine industry has undoubtedly contributed massively in the medical world, with hundreds of millions lives saved as a result successful development prophylactic and therapeutic vaccines against various infectious oncological diseases. Simultaneously, there been an ongoing evolutionary battle between polymorphic microbes human immune system, have developed counter-responses host by creating diverse “holes” vulnerability innate system. Such mechanisms may resulted due to lower focus upon sharpening lines directly necessary. overall objective vaccine-development should be all departments that are targeted microbial agents for purpose transient suppression distribution count/load at systemic level. Likewise, it could viable clinical research community start focusing filling “gaps” now present pathways responsible proper natural activation proportionate signalling toward adaptive Perhaps, through such process, “road” which is “old” filled “holes”, gradually transformed into perfectly uniform “highway”, required signals transmitted robustly from before manage translate pathogenic proteins transiently prevent transmission altogether, until becomes too late response possibly develop non-harmful manner organism. scenario would possible, given almost impossible growth eventually stall not risk experiencing decrease result. important society bind principles maintaining healthy nature-friendly lifestyle, philosophical quote “We what we eat.” facilitation animal evolution over viral bacterial molecular self-camouflaging possible directions, sharper resulting actions “cost” such, patterns based models observed Physics, Newton’s Third Law Motion, well First Thermodynamics, concerns Conservation Energy.

Язык: Английский

Structure-Based Identification of SARS-CoV-2 nsp10-16 Methyltransferase Inhibitors Using Molecular Dynamics Insights DOI Creative Commons
Ahmad M. Alharbi

Current Issues in Molecular Biology, Год журнала: 2025, Номер 47(3), С. 198 - 198

Опубликована: Март 17, 2025

SARS-CoV-2 evades immune detection via nsp10-16 methyltransferase-mediated 2′-O-methylation of viral mRNA, making it a key antiviral target. Our study employed structure-based drug discovery—including virtual screening, molecular docking, and dynamics (MD) simulations—to identify potent inhibitors nsp10-16. We identified seven promising (Z1–Z7) targeting the binding site methyltransferase, with Z2, Z3, Z4, Z7 exhibiting strong affinities. Further, simulations confirmed that effectively stabilized enzyme by reducing conformational fluctuations maintaining structural compactness, comparable to native ligand-bound complex. The deviation revealed Z6, restricted large-scale transitions, reinforcing their stabilizing effect on enzyme. free energy calculations ranked Z4 (−37.26 kcal/mol), (−35.37 Z6 (−35.22 kcal/mol) as strongest binders, surpassing tubercidin complex (−23.70 kcal/mol). interactions analysis Asp99, Tyr132, Cys115 residues, forming high-lifetime hydrogen bonds. drug-likeness highlighted selected compounds candidates, high gastrointestinal absorption, optimal solubility, minimal CYP450 inhibition. Further experimental validation lead optimization are needed develop methyltransferase improved pharmacokinetics efficacy.

Язык: Английский

Процитировано

0
Infection-Simulator, Immunostimulatory and Immunomodulatory Effects of Interferons I and III in Biological Systems: A New Era in Vaccinology and Therapeutics Possible? DOI Open Access
Theodor-Nicolae Carp,

Michael Metoudi,

Vanshika Ojha

и другие.

Опубликована: Июль 10, 2024

The severe acquired respiratory coronavirus–2 (SARS–CoV-2) infection has initiated both acute and chronic COVID–19 disease between 2020 2023, currently evolving with other homologous prior coronavirus strains of the Nidoviridae order, which encompasses prevalent alpha/ beta coronaviruses, but also Middle East Respiratory Syndrome (MERS-CoV) SARS-CoV-1, recent SARS–CoV–2 variants, increasing demands for effective immunogens therapeutic approaches that will reduce global burden further from SARS–CoV-2 affected individuals may experience post sequelae (PASC) or “Long COVID”. Following a worldwide programme prophylactic vaccination, there is still dilemma in efforts to find early would treat novel SARS-CoV-2 variants prevent future epidemics pandemics within host human animal populations, where zoonotic cross species transfer naturally occurs. Concerns about viral immune escape intersect at specific point; gained evolutionary ability several viruses co–infect compete against previous scientific advances since 1796 remain undetected asymptomatic during stages progressing symptomatic via double methylation 5' end eukaryotic DNA RNA-based genomes, 7-MeGpppA2’-O-Me cap, its capping process performed by activated 2’ - O Methyltransferase (MTase) enzyme, complex two non-structural proteins (NSPs) joined together through an activation (NSP10/16) N7-Methyltransferase (N7-MTase/NSP14), respectively. Moreover, it was discovered polymorphic translate NSP1, prevents various Pattern Recognition Receptors (PRRs), consequently, detection Pathogen-Associated Molecular Patterns (PAMPs) Damage-Associated (DAMPs) alike. NSP1 silences important interferon-encoding genes (INGs) interferon-stimulated (ISGs), signalled paracrine manner neighbouring cells, induces apoptosis inducing effect “trace erase” making as immunologically “invisible” possible initial, key replication distribution, all such mechanisms occurring independently cause. Another NSP NSP14, plays functional roles are independent each other; produce new genetic material purpose maintaining validity genome well, not just methyl group 5’ genome. Other NSPs share role 10, 14 16 directly suppressing PRRs ISGs, help virus self-camouflaging first- second-line immunity, thereby often severely impacting quality produced adaptive responses. outcome phenomena sharp decrease Type I III interferons' (IFNs) rate synthesis usually occur affect homeostatic cellular pathways, resulting induced apoptosis. Nonetheless, effects microbial evasion development carcinogenic pathologies widely known. In short, developed proportionate response responses, relying on gaps mostly situated natural system their molecular self-camouflaging. Scientists numerous treatment generally showed good success rates fewer risks adverse events, present COVID-19 research should be taken into consideration whilst filtering most appropriate solutions. For example, administration recombinant interferons nasal mucosa layer, mediators anti–viral activity, can simulate intracellular stimulate activity timely manner, training innate cells develop appropriately adequate B T cells. example could involve lymphocytes low dose IFNs possibly III, insertion lymphatic system, alongside additional recruitment plasmacytoid dendritic (pDCs) interferon “factories”, management. It might focusing offering information genetics protein structure pathogen, rather than first-line faster, excessively increases specificity, reach level brings opportunity evolve previously-developed mechanisms. until community realises this potentially crucial aspect large proportions world population probably continue face serious diseases over coming decades, evidenced dengue fever more recently, monkeypox avian flu. Of note, been indicated IFN / display significant immunising, clinical onset-attenuating many evoked diseases, well number oncological diseases.

Язык: Английский

Процитировано

3
Potential Innovations in Modern-Day Human and Animal Vaccine Development DOI Open Access
Theodor-Nicolae Carp

Опубликована: Июль 26, 2024

The vaccine industry has undoubtedly contributed massively in the medical world, with hundreds of millions lives saved as a result successful development prophylactic and therapeutic vaccines against various infectious oncological diseases. Simultaneously, there been an ongoing evolutionary battle between polymorphic microbes human immune system, have developed counter-responses host by creating diverse “holes” vulnerability innate system. Such mechanisms may resulted due to lower focus upon sharpening lines directly necessary. overall objective vaccine-development should be all departments that are targeted microbial agents for purpose transient suppression distribution count/load at systemic level. Likewise, it could viable clinical research community start focusing filling “gaps” now present pathways responsible proper natural activation proportionate signalling toward adaptive Perhaps, through such process, “road” which is “old” filled “holes”, gradually transformed into perfectly uniform “highway”, required signals transmitted robustly from before manage translate pathogenic proteins transiently prevent transmission altogether, until becomes too late response possibly develop non-harmful manner organism. scenario would possible, given almost impossible growth eventually stall not risk experiencing decrease result. important society bind principles maintaining healthy nature-friendly lifestyle, philosophical quote “We what we eat.” facilitation animal evolution over viral bacterial molecular self-camouflaging possible directions, sharper resulting actions “cost” such, patterns based models observed Physics, Newton’s Third Law Motion, well First Thermodynamics, concerns Conservation Energy.

Язык: Английский

Процитировано

1