The pathological maelstrom of COVID-19 and cardiovascular disease

Nature Cardiovascular Research, Год журнала: 2022, Номер 1(3), С. 200 - 210

Опубликована: Март 16, 2022

Язык: Английский

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Therapeutic potential of melatonin and melatonergic drugs on K18‐hACE2 mice infected with SARS‐CoV‐2

Journal of Pineal Research, Год журнала: 2021, Номер 72(1)

Опубликована: Сен. 29, 2021

As the COVID-19 pandemic grows, several therapeutic candidates are being tested or undergoing clinical trials. Although prophylactic vaccination against SARS-CoV-2 infection has been shown to be effective, no definitive treatment exists date in event of infection. The rapid spread by and its variants fully warrants continued evaluation drug treatments for COVID-19, especially context repurposing already available safe drugs. Here, we explored potential melatonin melatonergic compounds attenuating pathogenesis mice expressing human ACE2 receptor (K18-hACE2), strongly susceptible Daily administration melatonin, agomelatine, ramelteon delays occurrence severe outcome with improvement survival, high dose. changes most lung inflammatory cytokines observed, limits exacerbated local production type I III interferons, which is likely associated observed improved symptoms treated mice. promising results from this preclinical study should encourage studies examining benefits drugs treat related diseases humans.

Язык: Английский

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Bovine lactoferrin inhibits SARS‐CoV‐2 and SARS‐CoV‐1 by targeting the RdRp complex and alleviates viral infection in the hamster model

Journal of Medical Virology, Год журнала: 2022, Номер 95(1)

Опубликована: Ноя. 4, 2022

Abstract Breast milk has been found to inhibit coronavirus infection, while the key components and mechanisms are unknown. We aimed determine that contribute antiviral effects of breastmilk explore their potential mechanism. Lactoferrin (Lf) fat globule membrane severe acute respiratory syndrome 2 (SARS‐CoV‐2)‐related GX_P2V transcription‐ replication‐competent SARS‐CoV‐2 virus‐like particles in vitro block viral entry into cells. confirmed bovine Lf (bLf) blocked binding between human angiotensin‐converting enzyme spike protein by combining receptor‐binding domain (RBD). Importantly, bLf inhibited RNA‐dependent RNA polymerase (RdRp) activity both SARS‐CoV nanomolar range. So far, no biological macromolecules have reported RdRp. Our result indicated plays a major role inhibiting replication. treatment reduced load lungs tracheae alleviated pathological damage. study provides evidence prevents infection RBD coronaviruses' RdRp activity, may be promising candidate for disease 2019.

Язык: Английский

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Quantitative proteomics of hamster lung tissues infected with SARS‐CoV‐2 reveal host factors having implication in the disease pathogenesis and severity

The FASEB Journal, Год журнала: 2021, Номер 35(7)

Опубликована: Июнь 9, 2021

Syrian golden hamsters (Mesocricetus auratus) infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) manifests lung pathology. In this study, efforts were made to check the infectivity of a local SARS-CoV-2 isolate in self-limiting and non-lethal hamster model evaluate differential expression proteins during infection convalescence. The findings study confirm vivo. Analysis clinical parameters tissue samples show pathophysiological manifestation similar that reported earlier COVID-19 patients with other isolates. However, diffuse alveolar damage (DAD), common histopathological feature human was only occasionally noticed. lung-associated pathological changes very prominent on 4th day post-infection (dpi), mostly resolved 14 dpi. Here, we carried out quantitative proteomic analysis tissues from SARS-CoV-2-infected 4 post-infection. This resulted identification 1585 which 68 significantly altered between both groups. Pathway revealed complement coagulation cascade, platelet activation, ferroptosis, focal adhesion as top enriched pathways. addition, also identified two pulmonary surfactant-associated (Sftpd Sftpb), known for their protective role function. Together, these will aid understanding mechanism(s) involved pathogenesis progression disease.

Язык: Английский

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Pathology and Immunity After SARS-CoV-2 Infection in Male Ferrets Is Affected by Age and Inoculation Route

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Окт. 21, 2021

Improving COVID-19 intervention strategies partly relies on animal models to study SARS-CoV-2 disease and immunity. In our pursuit establish a model for severe COVID-19, we inoculated young adult male ferrets intranasally or intratracheally with SARS-CoV-2. Intranasal inoculation established an infection in all ferrets, viral dissemination into the brain gut. Upon intratracheal only became infected. However, neither route induced observable symptoms. Despite this, persistent inflammation nasal turbinates was prominent especially follicular hyperplasia bronchi developed 21 days post infection. These effects -if sustained- might resemble long-COVID. Respiratory systemic cellular responses antibody were animals We conclude that intranasally-infected asymptomatic possibly aspects of Combined increasing portfolio measure adaptive immunity, are relevant vaccine research.

Язык: Английский

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Development of a Hamster Natural Transmission Model of SARS-CoV-2 Infection

Viruses, Год журнала: 2021, Номер 13(11), С. 2251 - 2251

Опубликована: Ноя. 9, 2021

The global pandemic of coronavirus disease (COVID-19) caused by infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to an international thrust study pathogenesis and evaluate interventions. Experimental hamsters the resulting is one preferred animal models since clinical signs virus shedding are similar more cases human COVID-19. main route challenge been direct inoculation via intranasal route. To resemble natural infection, we designed a bespoke transmission cage system assess whether recipient animals housed in physically separate adjacent cages could become infected from challenged donor central cage, equal airflow across two side cages. optimise viral animals, low moderate dose were compared after challenge, but responses observed no discernible difference kinetics. results our set-up demonstrate that most within developed, variation kinetics levels between individual animals. Common outputs used for assessment directly-challenged hamsters, such as weight loss, less obvious who naturally acquiring infection. utility model further work on assessing differences strains evaluating interventions using which closely resembles

Язык: Английский

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Calpeptin is a potent cathepsin inhibitor and drug candidate for SARS-CoV-2 infections

Communications Biology, Год журнала: 2023, Номер 6(1)

Опубликована: Окт. 18, 2023

Several drug screening campaigns identified Calpeptin as a candidate against SARS-CoV-2. Initially reported to target the viral main protease (Mpro), its moderate activity in Mpro inhibition assays hints at second target. Indeed, we show that is an extremely potent cysteine cathepsin inhibitor, finding additionally supported by X-ray crystallography. Cell infection proved Calpeptin's efficacy Treatment of SARS-CoV-2-infected Golden Syrian hamsters with sulfonated dose 1 mg/kg body weight reduces load trachea. Despite higher risk side effects, intrinsic advantage targeting host proteins their mutational stability contrast highly mutable targets. Here cathepsins, protein family organism, calpeptin promising approach for treatment SARS-CoV-2 and potentially other infections.

Язык: Английский

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BPR3P0128, a non-nucleoside RNA-dependent RNA polymerase inhibitor, inhibits SARS-CoV-2 variants of concern and exerts synergistic antiviral activity in combination with remdesivir

Antimicrobial Agents and Chemotherapy, Год журнала: 2024, Номер 68(4)

Опубликована: Март 6, 2024

ABSTRACT Viral RNA-dependent RNA polymerase (RdRp), a highly conserved molecule in viruses, has recently emerged as promising drug target for broad-acting inhibitors. Through Vero E6-based anti-cytopathic effect assay, we found that BPR3P0128, which incorporates quinoline core similar to hydroxychloroquine, outperformed the adenosine analog remdesivir inhibiting RdRp activity (EC 50 = 0.66 µM and 3 µM, respectively). BPR3P0128 demonstrated broad-spectrum against various severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern. When introduced after viral adsorption, significantly decreased SARS-CoV-2 replication; however, it did not affect early entry stage, evidenced by time-of-drug-addition assay. This suggests BPR3P0128’s primary action takes place during replication. We also effectively reduced expression proinflammatory cytokines human lung epithelial Calu-3 cells infected with SARS-CoV-2. Molecular docking analysis showed targets channel, substrate entry, implies operates differently—but complementary—with remdesivir. Utilizing an optimized cell-based minigenome reporter confirmed exhibited potent inhibitory activity. However, enzyme-based assay employing purified recombinant nsp12/nsp7/nsp8 failed corroborate this may inhibit targeting host-related RdRp-associated factors. Moreover, discovered combination had synergistic effect—a result likely due both drugs interacting separate domains RdRp. novel synergy between two reinforces potential clinical value BPR3P0128-remdesivir combating

Язык: Английский

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Cold atmospheric plasma for preventing infection of viruses that use ACE2 for entry

Theranostics, Год журнала: 2022, Номер 12(6), С. 2811 - 2832

Опубликована: Янв. 1, 2022

The mutating SARS-CoV-2 potentially impairs the efficacy of current vaccines or antibody-based treatments. Broad-spectrum and rapid anti-virus methods feasible for regular epidemic prevention against COVID-19 alike are urgently called for.

Язык: Английский

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Mouse models in COVID-19 research: analyzing the adaptive immune response

Medical Microbiology and Immunology, Год журнала: 2022, Номер 212(2), С. 165 - 183

Опубликована: Июнь 4, 2022

The emergence of SARS-CoV-2, the severe acute respiratory syndrome coronavirus type 2 causing COVID-19 pandemic, resulted in a major necessity for scientific countermeasures. Investigations revealing exact mechanisms SARS-CoV-2 pathogenesis provide basis development therapeutic measures and protective vaccines against COVID-19. Animal models are inevitable infection pre-clinical vaccination studies as well testing. A well-suited animal model, mimicking pathology seen human patients, is an important these investigations. Several were already used during with different clinical outcomes after infection. Here, we give overview focus on mouse model. Mice well-established model laboratory use several have been generated being studies. Furthermore, analysis SARS-CoV-2-specific T cells mice highlighted.

Язык: Английский

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