Anonymous ID: cc2d7a June 21, 2022, 8:27 a.m. No.16482986   🗄️.is 🔗kun   >>2995 >>3029 >>3052

>>16482647 (pb) Vax 2.0, Here We Go: Moderna Announces “Human Trials” ofNew Hybrid Flu-Covid VaccineAre Officially Underway – Future “Triple-Threat” Vaccine “in the Works”

 

Virus Res. 2021 Apr 2;295:198277. doi: 10.1016/j.virusres.2020.198277. Epub 2021 Jan 18.

 

Repurposing of antiparasitic niclosamide to inhibit respiratory syncytial virus (RSV) replication

 

PMID: 33476693 DOI: 10.1016/j.virusres.2020.198277

 

Abstract

 

Despite being an important health problem, there are only supportive care treatments for respiratory syncytial virus (RSV) infection. Thus, discovery of specific therapeutic drugs for RSV is still needed. Recently, an antiparasitic drug niclosamide has shown a broad-spectrum antiviral activity. Here, our in vitro model was used to study the antiviral effect of niclosamide on RSV and its related mechanism. Niclosamide inhibited RSV with time and dose-dependent manner. Pretreatment with submicromolar concentration of niclosamide for 6 h presented the highest anti-RSV activity of 94 % (50 % effective concentration; EC50 of 0.022 μM). Niclosamide efficiently blocked infection of laboratory strains and clinical isolates of both RSV-A and RSV-B in a bronchial epithelial cell line. Although a disruption of the mechanistic target of rapamycin complex 1 (mTORC1) pathway by niclosamide was previously hypothesized as a mechanism against pH-independent viruses like RSV, using a chemical mTORC1 inhibitor, temsirolimus, and a chemical mTORC1 agonist, MHY1485 (MHY), we show here that the mechanism of RSV inhibition by niclosamide was mTORC1 independent. Indeed, our data indicated that niclosamide hindered RSV infection via proapoptotic activity by a reduction of AKT prosurvival protein, activation of cleaved caspase-3 and PARP (poly ADP-ribose polymerase), and an early apoptosis induction.

 

Keywords: Broad-spectrum antiviral activity; Drug repurposing; Niclosamide; Proapoptotic activity; RSV; pH-independent viruses.

 

https://pubmed.ncbi.nlm.nih.gov/33476693/

Anonymous ID: cc2d7a June 21, 2022, 8:32 a.m. No.16482995   🗄️.is 🔗kun   >>3389 >>3569

>>16482986

 

Viruses. 2019 Aug 11;11(8):739. doi: 10.3390/v11080739.

 

Antibiotic Minocycline Prevents Respiratory Syncytial Virus Infection

 

Swapnil S Bawage 1 , Pooja M Tiwari 1 , Shreekumar Pillai 1 , Vida A Dennis 1 , Shree R Singh 2

 

PMID: 31405261 PMCID: PMC6723987 DOI: 10.3390/v11080739

 

Abstract

 

Treatment drugs, besides their specific activity, often have multiple effects on the body. The undesired effect of the drug may be repurposed as therapeutics, saving significant investigative time and effort. Minocycline has anti-cancer, anti-oxidant, anti-inflammatory, and anti-apoptotic properties. Presently, minocycline is also known to show anti-viral activity against Influenza virus, Japanese encephalitis virus, Simian immunodeficiency virus, Human immunodeficiency virus and West Nile virus. Here, we investigate the effect of minocycline on Respiratory syncytial virus (RSV), a common respiratory virus that causes severe mortality and morbidity in infants, children, and older adult populations. Currently, there is no effective vaccine or treatment for RSV infection; hence, there is a critical need for alternative and effective drug choices. Our study shows that minocycline reduces the RSV-mediated cytopathic effect and prevents RSV infection. This is the first study demonstrating the anti-viral activity of minocycline against RSV.

 

Keywords: Parkin-Ubiquitin pathway; RSV; antibiotics; antiviral; bronchiolitis; minocycline; neurodegenerative diseases; pneumonia; respiratory diseases.

 

https://pubmed.ncbi.nlm.nih.gov/31405261/

Anonymous ID: cc2d7a June 21, 2022, 8:37 a.m. No.16483029   🗄️.is 🔗kun

>>16482986

Novavax craters after Phase III RSV F vaccine failure; seeks path forward

By Ben AdamsSep 16, 2016 01:41am

 

Novavax ($NVAX) saw its shares plummet afterhours yesterday when it announced a late-stage test of its infectious respiratory disease vaccine missed all of its marks across the 12,000-strong study.

 

In top-line data released just after the markets closed, the biotech’s RSV F-protein recombinant nanoparticle vaccine candidate failed to hit both its primary and secondary objectives, and most damning of all, did not demonstrate vaccine efficacy in the Phase III Resolve trial.

 

The drug was seeking to treat adults with respiratory syncytial virus (RSV), a respiratory infectious disease that causes serious infection of the respiratory tract, similar to influenza. The virus puts more than 200,000 over-65s in the hospital each year, and accounts for around 16,000 deaths in that age range.

 

Just over a year ago the company had far better newsone which saw its shares surgeafter posting positive data from a large mid-stage study of its vaccine. The Phase II study showed that its vaccine was 46% effective in preventing lower respiratory tract infections and 44% effective against all symptoms of RSV disease.

 

Cue blockbuster projections and its president and CEO Stan Erck telling Reuters in August of last year that it could be "the largest selling vaccine in the history of vaccines in terms of revenue."

 

In a far more tempered tone, Erck said yesterday in a conference call that the latest Phase III data were “surprisingly flat.”

 

But there was no talk of dumping the program altogether, with Erck saying they will “continue to invest in this vaccine,” which he said based on patterns from other trials the vaccine can “stimulate a robust immune response…our vaccine works.”

 

Novavax is in addition to the adult studies also running mid-stage trials of its RSV F Vaccine to protect infants via maternal immunization. Glenn said on the call he didn’t think the issues with its Phase III in adults could be seen as a negative read-through for this program, which has been given a $89 million grant by the Bill & Melinda Gates Foundation.

 

There are other companies seeking to get a new RSV vax to market, with AstraZeneca’s ($AZN) MedImmune unit last April gaining an FDA fast track tag for its early-stage candidate MEDI7510.

 

https://www.fiercebiotech.com/biotech/novavax-craters-after-phase-iii-rsv-f-vaccine-failure-seeks-path-forward

Anonymous ID: cc2d7a June 21, 2022, 8:42 a.m. No.16483052   🗄️.is 🔗kun

>>16482986

Research shows why 1960s RSV shot sickened children

 

NEW YORK (Reuters Health) - Researchers from Johns Hopkins have solved the decades-old mystery of why a vaccine developed to prevent a common childhood viral infection wound up making kids sick.

The findings provide important clues to how to develop a safe, effective vaccine against respiratory syncytial virus (RSV), the main cause of wintertime hospital stays among babies and young children worldwide, Dr. Fernando P. Polack, the lead researcher on the study, told Reuters Health.

“A big concern for the scientists involved in RSV vaccine development is to make sure we do not repeat the same situation again,” said Polack, who is also affiliated with the INFANT Foundation in Buenos Aires.

 

In the late 1960s, children in Washington, DC received an RSV vaccine in which the virus was inactivated with formalin. Eighty percent of the children given the shot were hospitalized with severe respiratory disease, and two died. Many scientists had thought the formalin was responsible for the vaccine’s problems, but the chemical has been used safely in other vaccines.

 

For eight years, Polack and his team have been investigating why the vaccine caused the illness, known as enhanced respiratory disease, or ERD. They started by examining tissue from the lungs of the two patients who died, and comparing the effects of the vaccine to RSV itself in mice.

The problem, they report this month in the journal Nature Medicine, was that the children’s antibodies were not binding strongly enough to the inactivated virus to produce a protective immune response.Instead, the antibodies were dragging the dead virus with them, triggering a massive attack by other arms of the immune system.

The inactivated vaccine was only weakly stimulating molecules on the surfaces of cells that are responsible for recognizing infectious invaders and triggering an appropriate immune response, the researchers say. So an effective vaccine would need to do a better job of stimulating these molecules, known as Toll-like receptors, Polack explained.

Most likely, the researcher said, making an effective and safe RSV vaccine will require developing an attenuated form of the virus, meaning a strain that is too weak to cause infection but active enough to stimulate the Toll-like receptors adequately.

 

Such a vaccine is sorely needed, Polack said. Half of children develop RSV infections before their first birthdays, the researcher noted, while by age 2, 95 percent have been infected. About half the time, the infection only produces a cold, while in the other half of cases the infection enters the lungs and causes infection of the small airways, or bronchiolitis. A child will usually get better on his or her own, but in about one in 100 cases, the child will need to be hospitalized and be given oxygen. RSV kills a half million people worldwide every year.

 

SOURCE: Nature Medicine, online December 14, 2008.

 

https://www.reuters.com/article/us-rsv-shot-idUSTRE4BM4SH20081223