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Posts Tagged ‘antiviral drugs’

Non-toxic antiviral nanoparticles with a broad spectrum of virus inhibition

Curator and Reporter: Dr. Premalata Pati, Ph.D., Postdoc

Infectious diseases account for 20% of global deaths, with viruses accounting for over a third of these deaths (1). Lower respiratory effects and human immunodeficiency viruses (HIV) are among the top ten causes of death worldwide, both of which contribute significantly to health-care costs (2). Every year, new viruses (such as Ebola) increase the mortality toll. Vaccinations are the most effective method of avoiding viral infections, but there are only a few of them, and they are not available in all parts of the world (3). After infection, antiviral medications are the only option; unfortunately, only a limited number of antiviral medications are approved in this condition. Antiviral drugs on a big scale that can influence a wide spectrum of existing and emerging viruses are critical.

The three types of treatments currently available are small molecules (such as nucleoside analogues and peptidomimetics), proteins that stimulate the immune system (such as interferon), and oligonucleotides (for example, fomivirsen). The primary priorities include HIV, hepatitis B and C viruses, Herpes Simplex Virus (HSV), human cytomegalovirus (HCMV), and influenza virus. They work mainly on viral enzymes, which are necessary for viral replication but which differ from other host enzymes to ensure selective function. The specificity of antivirals is far from perfect because viruses rely on the biosynthesis machinery for reproduction of infected cells, which results in a widespread and inherent toxicity associated with such therapy. However, most viruses mutate rapidly due to their improper replicating mechanisms and so often develop resistance (4). Finally, since antiviral substances are targeted at viral proteins, it is challenging to build broad-based antivirals that can act with a wide range of phylogenetic and structurally different virus.

Over the last decade breakthroughs in nanotechnology have led to scientists developing incredibly specialized nanoparticles capable of traveling in specific cells through a human body. A broad spectrum of destructive viruses is being targeted and not only bind to, but also destroy, by modern computer modeling technology.

An international team of researchers led by the University of Illinois at Chicago chemistry professor Petr Kral developed novel anti-viral nanoparticles that bind to a variety of viruses, including herpes simplex virus, human papillomavirus, respiratory syncytial virus, Dengue, and lentiviruses. In contrast to conventional broad-spectrum antivirals, which just prevent viruses from invading cells, the new nanoparticles eradicate viruses. The team’s findings have been published in the journal “Nature Materials.”

A molecular dynamics model showing a nanoparticle binding to the outer envelope of the human papillomavirus. (Credit: Petr Kral) https://today.uic.edu/files/2017/09/viralbindingcropped.png

The goal of this new study was to create a new anti-viral nanoparticle that could exploit the HSPG binding process to not only tightly attach with virus particles but also to destroy them. The work was done by a group of researchers ranging from biochemists to computer modeling experts until the team came up with a successful nanoparticle design that could, in principle, accurately target and kill individual virus particles.

The first step to combat many viruses consists in the attachment of heparin sulfate proteoglycan on cell surfaces to a protein (HSPG). Some of the antiviral medications already in place prevent an infection by imitating HSPG’s connection to the virus. An important constraint of these antivirals is that not only is this antiviral interaction weak, it does not kill the virus.

Kral said

We knew how the nanoparticles should bind on the overall composition of HSPG binding viral domains and the structures of the nanoparticles, but we did not realize why the various nanoparticles act so differently in terms of their both bond strength and viral entry in cells

Kral and colleagues assisted in resolving these challenges and guiding the experimentalists in fine-tuning the nanoparticle design so that it performed better.

The researchers have employed advanced computer modeling techniques to build exact structures of several target viruses and nanoparticles up to the atom’s position. A profound grasp of the interactions between individual atom groupings in viruses and nanoparticles allows the scientists to evaluate the strength and duration of prospective links between these two entities and to forecast how the bond could change over time and eventually kill the virus.


Atomistic MD simulations of an L1 pentamer of HPV capsid protein with the small NP (2.4 nm core, 100 MUP ligands). The NP and the protein are shown by van der Waals (vdW) and ribbon representations respectively. In the protein, the HSPG binding amino acids are displayed by vdW representation.

Kral added

We were capable of providing the design team with the data needed to construct a prototype of an antiviral of high efficiency and security, which may be utilized to save lives

The team has conducted several in vitro experiments following the development of a prototype nanoparticle design which have demonstrated success in binding and eventually destroying a wide spectrum of viruses, including herpes simplex, human papillomaviruses, respiratory syncytial viruses and dengue and lentiviruses.

The research is still in its early phases, and further in vivo animal testing is needed to confirm the nanoparticles’ safety, but this is a promising new road toward efficient antiviral therapies that could save millions of people from devastating virus infections each year.

The National Centers of Competence in Research on Bio-Inspired Materials, the University of Turin, the Ministry of Education, Youth and Sports of the Czech Republic, the Leenards Foundation, National Science Foundation award DMR-1506886, and funding from the University of Texas at El Paso all contributed to this study.

Main Source

Cagno, V., Andreozzi, P., D’Alicarnasso, M., Silva, P. J., Mueller, M., Galloux, M., … & Stellacci, F. (2018). Broad-spectrum non-toxic antiviral nanoparticles with a virucidal inhibition mechanism. Nature materials17(2), 195-203. https://www.nature.com/articles/nmat5053

Other Related Articles published in this Open Access Online Scientific Journal include the following:

Rare earth-doped nanoparticles applications in biological imaging and tumor treatment

Reporter: Irina Robu, PhD

https://pharmaceuticalintelligence.com/2020/10/04/rare-earth-doped-nanoparticles-applications-in-biological-imaging-and-tumor-treatment/

Nanoparticles Could Boost Effectiveness of Allergy Shots

Reporter: Irina Robu, PhD

https://pharmaceuticalintelligence.com/2019/05/25/nanoparticles-could-boost-effectiveness-of-allergy-shots/

Immunoreactivity of Nanoparticles

Author: Tilda Barliya PhD

https://pharmaceuticalintelligence.com/2012/10/27/immunoreactivity-of-nanoparticles/

Nanotechnology and HIV/AIDS Treatment

Author: Tilda Barliya, PhD

https://pharmaceuticalintelligence.com/2012/12/25/nanotechnology-and-hivaids-treatment/

Nanosensors for Protein Recognition, and gene-proteome interaction

Curator: Larry H Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2016/01/30/nanosensors-for-protein-recognition-and-gene-proteome-interaction/

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Race to develop antibody drugs for COVID-19

Reporter: Irina Robu, PhD

Even at the record pace vaccines are moving, the first vaccine for COVID-19 might not be available until next year. And even if it is available, it will take longer for enough people within the population to be vaccinated in order to achieve herd immunity and curb the spread. Companies such as Regeneron, Eli Lily, Amgen and Vir Biotechnology are leading the race to produce therapies that could give patients infected with COVID-19 short term protection. However, several experts believe that developing antibody drugs are vital.
At this time, Gilead’s antiviral drug remdesivir, which seems to help hasten recovery from COVID-19, but not entirely. There is no guarantee that these injectable biologic drugs won’t solve the pandemic. Yet, many believe that in combination with mass testing and tracing measures, these injectable biologic drugs could be a critical tool for keeping the disease in check.

When fighting off foreign invaders, our bodies make antibodies precisely produced for the task. The reason vaccines offer such long-lasting protection is they train the immune system to identify a pathogen, so immune cells remember and are ready to attack the virus when it appears. Monoclonal antibodies for coronavirus would take the place of the ones our bodies might produce to fight the disease. The manufactured antibodies would be infused into the body to either tamp down an existing infection, or to protect someone who has been exposed to the virus.

However, these drugs are synthetic versions of the convalescent plasma treatments that rely on antibodies from people who have recovered from infection. But the engineered versions are easier to scale because they’re manufactured in rats, rather than from plasma donors.

Yet, what brands antibodies unique in comparison to vaccines or antiviral drugs is their potential to both treat and protect against viral infections and could work as a short-term preventative for healthcare workers who are at high risk of contracting COVID-19 or as a treatment for people who are already sick. But it is up to creators to figure out exactly when is the best time is to interfere with an antibody drug. More persuasively, antibodies will deliver the greatest value for the people at the highest risk like healthcare workers or people who are old or immuno-compromised.

Over the years of research, it is shown that some vaccines are only effective in a part of population. But making a vaccine takes time, and they don’t kick in immediately. So, proving the monoclonal antibodies can treat patients with COVID-19 disease can be much faster and easier than showing a preventive benefit. As with vaccines, antibodies would have to succeed in much longer tests to fully show they can prevent infections. Vaccine aside, the only treatments granted emergency use by the FDA thus far are the antiviral remdesivir and the generic malaria pill hydroxychloroquine.

Regeneron, Amgen, Vir and Eli Lilly are each using different methods to screen for and develop their antibodies. The initial experiments may lead to different type of products where one type of antibody versus a cocktail of two or three. The antibodies are designed to mimic the ones our bodies make versus those that are modified in some way to improve their properties. Modifying an antibody could help it last longer, but make it look more foreign to the immune system, which could lead to potential problems.
What makes antibodies unique compared to vaccines or antiviral drugs is their potential to both treat and protect against viral infections. The idea is that an antibody drug will bind to the “spike” protein SARS-CoV-2 uses to crack open cells, and prevent the virus from entering. The fastest path to success for an antibody is possible through a drug that has to be given intravenously in a hospital or clinic, rather than through an auto-injector a patient could self-administer.

SOURCE

https://www.biopharmadive.com/news/coronavirus-antibody-drug-trials/577778

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