Ivermectin for COVID-19 in adults in the community (PRINCIPLE): An open, randomised, controlled, adaptive platform trial of short- and longer-term outcomes

Journal of Infection, Journal Year: 2024, Volume and Issue: 88(4), P. 106130 - 106130

Published: Feb. 29, 2024

Language: Английский

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SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19 Morbidities and Therapeutics and for Vaccine Adverse Effects

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(24), P. 15480 - 15480

Published: Dec. 7, 2022

Experimental findings for SARS-CoV-2 related to the glycan biochemistry of coronaviruses indicate that attachments from spike protein glycoconjugates on surfaces red blood cells (RBCs), other and endothelial are key infectivity morbidity COVID-19. To provide further insight into these their potential clinical relevance, classic hemagglutination (HA) assay was applied using Wuhan, Alpha, Delta Omicron B.1.1.529 lineages mixed with human RBCs. The electrostatic central region four studied through molecular modeling simulations. Inhibition protein-induced HA tested macrocyclic lactone ivermectin (IVM), which is indicated bind strongly sites. results experiments were, first, induced HA. at a significantly lower threshold concentration than three prior much more electropositive its region. IVM blocked when added RBCs reversed afterward. These validate extend role bindings viral in They furthermore suggest therapeutic options competitive glycan-binding agents such as may help elucidate rare serious adverse effects (AEs) associated COVID-19 mRNA vaccines, use generated antigen.

Language: Английский

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Protein structure-based in-silico approaches to drug discovery: Guide to COVID-19 therapeutics

Molecular Aspects of Medicine, Journal Year: 2022, Volume and Issue: 91, P. 101151 - 101151

Published: Oct. 28, 2022

With more than 5 million fatalities and close to 300 reported cases, COVID-19 is the first documented pandemic due a coronavirus that continues be major health challenge. Despite being rapid, uncontrollable, highly infectious in its spread, it also created incentives for technology development redefined public needs research agendas fast-track innovations translated. Breakthroughs computational biology peaked during with renewed attention making all cutting-edge deliver agents combat disease. The demand develop effective treatments yielded surprising collaborations from previously segregated fields of science technology. long-standing pharmaceutical industry's aversion repurposing existing drugs lack exponential financial gain was overrun by crisis pressures front-line researchers providers. Effective vaccine even at an unprecedented pace took year commence trials. Now emergence variants waning protections booster shots resulting breakthrough infections continue strain care systems. As now, every protein SARS-CoV-2 has been structurally characterized related host pathways have extensively mapped out. community addressed druggability multitude possible targets. This made virtual computer-assisted drug as well new tools technologies such artificial intelligence leads. Here this article, we are discussing advances discovery field target-based exploring implications known target-specific on therapeutic management. current scenario calls personalized medicine efforts stratifying patient populations early their need different combinations prognosis-specific therapeutics. We intend highlight target hotspots potential agents, ultimate goal using rational design therapeutics not only end but uncover generalizable platform use future pandemics.

Language: Английский

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Herpesviruses reactivation following COVID-19 vaccination: a systematic review and meta-analysis

European journal of medical research, Journal Year: 2023, Volume and Issue: 28(1)

Published: Aug. 10, 2023

Abstract Background The reactivation of herpesviruses (HHV) in COVID-19 patients is evident the literature. Several reports have been published regarding these viruses (HSV, VZV, EBV, and CMV) among those who got vaccines. In this study, we aimed to review current evidence assess whether HHVs has any association with prior administration Methods A systematic search was conducted on 25 September 2022 PubMed/MEDLINE, Web Science, EMBASE. We included all observational studies, case reports, series which reported human following Results Our showed 80 articles that meet eligibility criteria. Among evaluated vaccines, most vaccines were mRNA based. Evidence from studies possible relation between vaccine VZV HSV reactivation. results our proportion meta-analysis rate received 14 persons per 1000 vaccinations (95% CI 2.97–32.80). Moreover, for 16 1.06–46.4). Furthermore, reports/series 149 cases HHV There several caused including BNT162b2 or Pfizer–BioNTech ( n = 76), Oxford-AstraZeneca 22), mRNA-1273 Moderna 17), Sinovac 4), BBIBP-CorV Sinopharm 3), Covaxin Covishield Johnson 1). Reactivated varicella-zoster virus (VZV) 114), cytomegalovirus (CMV) 15), herpes simplex (HSV) 14), Epstein-Barr (EBV) 6), HHV-6 2). Most their disease after first dose vaccine. Many having comorbidities, hypertension, diabetes mellitus, dyslipidemia, chicken pox, atrial fibrillation common. Conclusion conclusion, study vaccination herpesvirus supported by studies. However, other (EBV CMV), further research especially clinical trials required elucidate interaction

Language: Английский

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Time to Stop Using Ineffective Covid-19 Drugs

New England Journal of Medicine, Journal Year: 2022, Volume and Issue: 387(7), P. 654 - 655

Published: Aug. 17, 2022

Language: Английский

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Sialylated Glycan Bindings from SARS-CoV-2 Spike Protein to Blood and Endothelial Cells Govern the Severe Morbidities of COVID-19

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(23), P. 17039 - 17039

Published: Dec. 1, 2023

Consistent with well-established biochemical properties of coronaviruses, sialylated glycan attachments between SARS-CoV-2 spike protein (SP) and host cells are key to the virus’s pathology. SP attaches aggregates red blood (RBCs), as shown in many pre-clinical clinical studies, causing pulmonary extrapulmonary microthrombi hypoxia severe COVID-19 patients. heavily surfaces platelets (which, like RBCs, have no ACE2) endothelial (having minimal compound this vascular damage. Notably, experimentally induced RBC aggregation vivo causes same morbidities for COVID-19, including microvascular occlusion, clots, myocarditis. Key risk factors morbidity, older age, diabetes obesity, all characterized by markedly increased propensity clumping. For mammalian species, degree susceptibility correlates aggregability p = 0.033. five human betacoronaviruses, two common cold strains express an enzyme that releases attachments, while deadly SARS, MERS do not, although viral loads infections similar. These insights also explain previously puzzling efficacy certain generics against may support development future therapeutic strategies long COVID

Language: Английский

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SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19 Morbidities and Therapeutics and for Vaccine Adverse Effects

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Nov. 28, 2022

ABSTRACT Experimental findings for SARS-CoV-2 related to the glycan biochemistry of coronaviruses indicate that attachments from spike protein glycoconjugates on surfaces red blood cells (RBCs), other and endothelial are key infectivity morbidity COVID-19. To provide further insight into these their potential clinical relevance, classic hemagglutination (HA) assay was applied using Wuhan, Alpha, Delta Omicron B.1.1.529 lineages mixed with human RBCs. The electrostatic central region four studied through molecular modeling simulations. Inhibition protein-induced HA tested macrocyclic lactone ivermectin (IVM), which is indicated bind strongly sites. results experiments were, first, induced HA. at a significantly lower threshold concentration than three prior much more electropositive its region. IVM blocked when added RBCs reversed afterwards. These validate extend role bindings viral in They furthermore suggest therapeutic options competitive glycan-binding agents such as may help elucidate rare serious adverse effects (AEs) associated COVID-19 mRNA vaccines use generated antigen.

Language: Английский

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The effect of COVID‐19 and COVID‐19 vaccination on serum anti‐Mullerian hormone: A systematic review and meta‐analysis

Immunity Inflammation and Disease, Journal Year: 2024, Volume and Issue: 12(1)

Published: Jan. 1, 2024

The current study aims to evaluate the impact of COVID-19 infection and vaccination on ovarian reserve by detecting anti-Mullerian hormone (AMH) level.

Language: Английский

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Spironolactone as an adjuvant treatment for COVID-19: a systematic review and meta-analysis

Future Virology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 8

Published: Feb. 11, 2025

Language: Английский

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A Systematic Review of the Role of Purinergic Signalling Pathway in the Treatment of COVID-19

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 7865 - 7865

Published: April 26, 2023

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome 2 (SARS-CoV-2), has become a global health concern. Three years since its origin, despite the approval of vaccines and specific treatments against this new coronavirus, there are still high rates infection, hospitalization, mortality in some countries. COVID-19 is characterised inflammatory state coagulation disturbances that may be linked to purinergic signalling molecules such as adenosine triphosphate (ATP), diphosphate (ADP), (ADO), receptors (P1 P2). These nucleotides/nucleosides play important roles cellular processes, immunomodulation, blood clot formation, vasodilation, which affected during SARS-CoV-2 infection. Therefore, drugs targeting pathway, currently used for other pathologies, being evaluated preclinical clinical trials COVID-19. In review, we focus on potential these control release, degradation, reuptake extracellular nucleotides nucleosides treat Drugs P1 could have therapeutic efficacy due their capacity modulate cytokine storm immune response. Those acting P2X7, NLRP3 inflammasome activation, also valuable candidates they can reduce release pro-inflammatory cytokines. However, according available data, most promising medications treatment those platelets behaviour factors, mainly through P2Y12 receptor.

Language: Английский

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