Retrained generic antibodies can recognize SARS-CoV-2

 The SARS-CoV-2, the new coronavirus behind the current pandemic, infects humans by binding its surface-exposed spike proteins to ACE2 receptors exposed on the cell membranes.

Upon a vaccination or a real infection, it takes several weeks before the immunity develops antibodies that can selectively bind to these spike proteins. Such antibody-labeled viruses are neutralized by the natural killer and T cells operated by the human immunity.

An alternative approach to train the immunity response is offered by researchers at the University of Illinois Chicago and California State University at Sacramento who have developed a novel strategy that redirects antibodies for other diseases existing in humans to the spike proteins of SARS-CoV-2.

In their study published by the Journal of Physical Chemistry Letters, the team proposes using peptide-based double-faced "booster" inhibitors, with one face binding to the spike proteins of SARS-CoV-2 and the other face binding to generic hepatitis B antibodies.

"Once the SARS-CoV-2 viruses become labeled by the hepatitis B antibodies via intermediate boosters, the viruses will be neutralized. This universal approach allows a dramatic shortening of the response time upon real infections, which can be critical in certain patients or conditions," said Petr Král, UIC professor of chemistry, physics, pharmaceutical sciences and chemical engineering, and senior author on the paper.

Král and Yanxiao Han, who recently earned a Ph.D. in chemistry at UIC and is first author on the paper, believe the study could provide guidance in the preparation of generic therapeutics against emerging pathogens with the combined advantages of small-protein and antibody therapies.

"The dramatic impact which novel viruses can have on humans could be fast mitigated in the absence of their vaccination if generic antibodies present within them are temporarily retrained to recognize these viruses," the researchers wrote.

In a study published last spring, Král and Han extracted different peptides from ACE2 that interact directly with the viral spike protein.

"We investigated potential COVID-19 therapeutics using computer simulations based on the X-ray crystal structure of the receptor-binding domain of SARS-CoV-2 when it is bound to ACE2," Král said. "Similar to our latest study, identifying these kinds of inhibitors could lead to new treatments to combat the coronavirus."

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Co-author on the paper is Katherine McReynolds of California State University at Sacramento.

This work is supported by funding from the UIC Center for Clinical and Translational Science.

https://www.eurekalert.org/pub_releases/2021-02/uoia-rga020221.php

Israel data shows Pfizer jab stops illness, effect on transmissions unclear

 Initial data from Israel's coronavirus vaccination campaign shows the Pfizer/BioNTech jab protects against serious illness, but it is not yet clear whether it slows transmissions or spells progress toward achieving herd immunity, experts say.

The Jewish state is carrying out what is widely described as the world's fastest vaccination campaign per capita, watched closely by experts worldwide.

While many countries are struggling with procurement, Israel has made remarkable progress since launching inoculations in December.

So far, it has given the first of the two recommended doses of Pfizer jabs to roughly 35 percent of its nine-million population.

About 1.8 million have also received the second jab, mostly those over 60.

The health ministry announced that beginning Thursday, all Israelis aged 16 and over would be able to set an appointment to be vaccinated, dropping the age limit from its previous minimum of 35.

In a statement, the ministry stressed Wednesday that Israel's four health service providers should still focus their efforts on inoculating people aged 50 and over, as well as housebound Israelis.

Israel secured its substantial stock by paying above market price and by striking a data-sharing deal with Pfizer.

The agreement stipulates that Israel, which has one of the world's most sophisticated medical data systems, will share real-time information with Pfizer on the vaccine's impact, including on progress towards herd immunity.

Direct vs indirect protection

Ran Balicer, chairman of Israel's national expert panel on Covid-19, told AFP it was crucial to distinguish between the vaccine's two impacts.

The first is "the direct effect", of vaccinated people becoming "protected against symptomatic illness and severe disease", he said.

The second, "indirect effect" refers to the vaccine providing enough immunity to enough people that it forms an "epidemiological barrier" against transmission, he said.

Balicer, also the chief innovation officer at Clalit, Israel's largest health maintenance organisation (HMO), said the data shows the vaccine reduces serious illness, but the transmission question remained open.

Gabi Barbash, a prominent public health expert currently with the Weizmann Institute of Science, agreed.

"We do know that vaccines are decreasing the incidence of severe disease. That's it," he told AFP.

"We do not know whether the vaccines are minimising transmission."

Phase IV

In November, Pfizer announced that Phase III trials had showed its vaccine was 95 percent effective against the virus.

Given the gravity of the pandemic, it received regulatory approval through an accelerated trial process, which has made Israel's more comprehensive data even more valuable.

The country's Maccabi Institute of Innovation and Research, linked to an HMO of the same name, published a paper this week that it described as "the first and largest Phase IV study on the effectiveness of the (Pfizer-BioNTech) vaccine".

Clalit and Maccabi are two of Israel's four HMOs, which collectively provide healthcare to the entire population.

The HMOs are directly responsible for vaccinations and collecting data on their impact.

Maccabi compared the incidence of Covid-19 in the 12 days after individuals receiving their first Pfizer shot against incidence 13 to 24 days after the jab.

It found a 51 percent reduction in the incidence of lab confirmed infections in the latter period.

"Two weeks after the first dose you see a significant reduction in infection but it is not complete," Gabriel Chodick, co-author of the Maccabi report, told AFP.

Moreover, Israel is only testing those who present coronavirus symptoms, not a randomised sample of the entire vaccinated population.

It does not therefore have comprehensive data on the number of vaccinated people carrying the virus without symptoms.

Two jabs

Pfizer recommends administering its vaccine in two doses, three weeks apart.

Israel has enough stocks to follow these recommendations, meaning it does not have data on whether the protective effect from just one jab increases after 24 days in the absence of a second jab.

Maccabi has also released preliminary data on the second jab's impact.

It showed that out of 248,000 people studied one week after receiving their second injection, only 66 mild coronavirus infections were registered.

While those figures point towards near-total protection, Maccabi has stressed this data has not been fully analysed.

Despite its vaccination campaign, Israel has continued to register daily caseloads above 5,000, despite a nationwide lockdown in place since December 27.

But compliance with and enforcement of the lockdown has been uneven, notably among ultra-Orthodox Jews who have persistently flouted public safety rules throughout the pandemic.

"If you look at the number of new identified positive corona cases per day, it has not decreased for the last month and half," Barbash said.

"So is it because the lockdown is not a (real) lockdown, or is it because the vaccine is not minimising transmission? No one can tell that."

https://medicalxpress.com/news/2021-02-israel-pfizer-jab-illness-effect.html

Potential antiviral treatment for COVID-19, other viruses, found

 Researchers from the University of Nottingham have discovered a novel antiviral property of a drug that could have major implications in how future epidemics / pandemics—including COVID-19—are managed.

The study, published in Viruses, shows that thapsigargin is a promising broad spectrum antiviral, highly effective against COVID-19 virus (SARS-CoV-2), a common cold coronavirus, respiratory syncytial virus (RSV) and the influenza A virus.

Given that acute respiratory virus infections caused by different viruses are clinically indistinguishable on presentation, an effective broad-spectrum that can target different virus types at the same time could significantly improve clinical management. An antiviral of this type could potentially be made available for community use to control active infection and its spread.

The study is a collaborative project led by Professor Kin-Chow Chang and experts at the University of Nottingham (Schools of Veterinary Medicine and Sciences, Biosciences, Pharmacy, Medicine, and Chemistry), and colleagues at the Animal and Plant Health Agency (APHA), China Agricultural University and the Pirbright Institute.

In this ground-breaking study, the team of experts found that the plant-derived antiviral, at small doses, triggers a highly effective broad-spectrum host-centred antiviral innate immune response against three major types of human respiratory viruses—including COVID-19.

The key features based on cell and animal studies, which make thapsigargin a promising antiviral are that it is:

• effective against viral infection when used before or during active infection
• able to prevent a virus from making new copies of itself in cells for at least 48 hours after a single 30-minute exposure.
• stable in acidic pH, as found in the stomach, and therefore can be taken orally, so could be administered without the need for injections or hospital admission.
• not sensitive to virus resistance.
• at least several hundred-fold more effective than current antiviral options.
• just as effective in blocking combined infection with coronavirus and influenza A virus as in single-virus infection.
• safe as an antiviral (a derivative of thapsigargin has been tested in prostate cancer).

Professor Chang said: "Whilst we are still at the early stages of research into this antiviral and its impact on how viruses such as COVID-19 can be treated, these findings are hugely significant.

"The current pandemic highlights the need for effective antivirals to treat active infections, as well as vaccines, to prevent the infection. Given that future pandemics are likely to be of animal origin, where animal to human (zoonotic) and reverse zoonotic (human to animal) spread take place, a new generation of antivirals, such as thapsigargin, could play a key role in the control and treatment of important viral infections in both humans and animals."

Indeed, influenza virus, coronavirus and RSV are global pathogens of humans as well as animals. Thapsigargin represents a lead compound in the development of a new generation of powerful host-centred antivirals (as opposed to conventional antiviral drugs that directly target viruses) that could even be adopted in a holistic "One Health" approach to control human and animal viruses.

Professor Chang adds: "Although more testing is clearly needed, current findings strongly indicate that thapsigargin and its derivatives are promising antiviral treatments against COVID-19 and influenza virus, and have the potential to defend us against the next Disease X pandemic."

https://medicalxpress.com/news/2021-02-scientists-uncover-potential-antiviral-treatment.html

Piper Sandler Upgrades Jazz Pharmaceuticals (JAZZ) to Overweight

 

Following GWPH Acquisition Deal

https://www.streetinsider.com/Upgrades/Piper+Sandler+Upgrades+Jazz+Pharmaceuticals+%28JAZZ%29+to+Overweight%2C+Following+GWPH+Acquisition+Deal/17909910.html

Clene Nanomedicine Secures Crucial Patent for Gold Nanocrystal MS Treatment

 Clene Nanomedicine was awarded a crucial patent from the U.S. Patent and Trademark Office for its patented clean-surfaced gold nanocrystals used for treating patients with multiple sclerosis.

The patent marks the first one the company has secured for its gold nanocrystal technology in multiple sclerosis, a neurological disease estimated to impact more than 1 million people in the United States. Clene is currently assessing its lead asset CNM-Au8 in a Phase II trial for the treatment of chronic optic neuropathy in multiple sclerosis.

CNM-Au8 is designed to catalyze bio cellular reactions, and so far the company has seen the asset live up to its promise in clinical studies. In Phase I studies, CNM-Au8 was deemed safe and in preclinical studies, the asset demonstrated both remyelination and neuroprotective effects.

Data published by Clene has shown that treatment of neuronal cultures with CNM-Au8 improves survival of neurons, protects neurite networks, decreases intracellular levels of reactive oxygen species and improves mitochondrial capacity in response to cellular stresses induced by multiple disease-relevant neurotoxins.

In an interview with BioSpace, Clene Chief Executive Officer Rob Etherington said the company is thrilled to have been awarded this patent. Because MS is one of the largest markets in neurodegenerative diseases, the patent is important to the company as it moves forward in its clinical studies.

“We have said from the beginning that what we are doing with nanotherapeutics is unique to Clene. This patent will allow us to exclude others from using a similar program for multiple sclerosis,” Etherington said.

Etherington explained that CNM-Au8 is not designed to target a specific protein, nor it is designed to block or antagonize something, like most drugs. Rather, Clene’s compound is designed to enhance the intracellular biological actions necessary to repair and reverse neuronal damage, Etherington said.

New data is expected from Clene’s REPAIR-MS Phase II study of CNM-Au8 in the second half of 2021. Prior interim results from this study showed CNM-Au8 was associated with improvements across key central nervous system (CNS) bioenergetic metabolites.

Additionally, Clene’s VISIONARY-MS Phase II study is evaluating the efficacy and safety of CNM-Au8 as a remyelinating and neuro-reparative treatment in stable relapsing MS patients with chronic visual impairment. Interim data from the VISIONARY-MS trial demonstrated notable, exposure-related median improvements in the primary endpoint. Completion of enrollment is expected by the end of 2021.

“While the only approved treatments for MS today are immunomodulators, we see an opportunity to treat MS through a completely different mechanism of action utilizing the therapeutic bioenergetic effects of catalytic gold nanocrystals, such as CNM-Au8,” Etherington said.

Clene Chief Scientific Officer Mark Mortenson said it’s important to have a strong defensive line of patents that protects state of matter claims for suspensions and solutions, as well as processes for making the materials, devices for conducting the unique electro-crystal chemistry processes, and methods of using the novel materials, such as in this instance of using clean-surfaced gold nanocrystals for treating patients with MS. The newly-awarded patent, the company’s 112^th, provides protection for about a decade with the possibility for an extension, he added. The patent marks the first one in the United States for the method of treating MS with CNM-Au8.

“It gives us a nice runway,” Mortenson noted.

In addition to the multiple sclerosis study, Clene is assessing CNM-Au8 in Parkinson’s disease and Amyotrophic Lateral Sclerosis (ALS).

Not only is the company developing its gold nanocrystal compound, Clene is developing a silver and zinc asset for COVID-19. CNM-AgZn17 is Clene’s second key asset intended for broad anti-viral and anti-microbial use. A Phase II study is planned in Brazil to treat acutely symptomatic non-hospitalized patients with COVID-19.

The patent award follows closely on the heels of a merger with Tottenham Acquisition I Limited that netted the company $31.9 million to advance its research and development. The reverse merger secured Clene a spot on the Nasdaq Stock Exchange under the ticker symbol CLNN.

Etherington said the company expects to report additional business and clinical milestones. Moretenson said the company anticipates different governments across the globe to act on about 30 different patent applications in the coming months and year.

“We remain excited about the potential of their platform to improve neurological function,” Etherington said.

https://www.biospace.com/article/clene-nanomedicine-secures-crucial-patent-for-gold-nanocrystal-ms-treatment/

Nestle CEO Seeks Ways to Help With COVID-19 Vaccine Roll Out

 Nestle is looking at ways to help pay for COVID-19 vaccines and projects to inoculate populations where the world's largest food company operates, Chief Executive Mark Schneider said on Tuesday.

The Swiss group said it has already donated extensively to the Red Cross and other organisations to help cover the financial cost of vaccination programmes, Schneider said, but would now look at going further.

"We will also try to find ways to either sponsor the payment for the vaccine or sponsor the way it gets applied in communities where we are present," Schneider told the Forum Horizon event in Lausanne.

"The price of a vaccine for an advanced economy is negligible...but to a developing country which has been struggling already with all the impacts of COVID, on top of that to pay for the vaccine and for the services to get it applied is going to be very significant," he added.

The specific details of how Nestle would help still needed to be worked out, Schneider said, describing the project as a "work in progress".

"The most important ingredient is not there, and that's the vaccine itself," he said.

The maker of KitKat chocolate bars and Nescafe instant coffee is also looking at stepping up protections for its own staff, after introducing rigid testing at its sites and making mask wearing mandatory.

The Swiss company would look at immunising its own workers against the new coronavirus as soon as possible. Nestle employs around 290,000 people around the world.

"As soon as it is possible, and in full compliance with all federal and cantonal laws, if there is a way to make a service like this available to our people on site, we would be the first ones to try and do it," Schneider said.

https://www.medscape.com/viewarticle/945124

EU drugs regulator begins rolling review of Novavax COVID-19 vaccine

 Europe's drugs regulator said on Wednesday its panel is reviewing Novavax's COVID-19 vaccine on a rolling basis, to speed up potential approvals as the region reels from surging infections due to new variations of the virus.

The human medicines committee of the European Medicines Agency will review data from ongoing trials of the U.S.-based company's vaccine, NVX-CoV2373, as they become available until there was enough for conditional approval, the regulator said. (https://bit.ly/2Len9jR)

https://www.marketscreener.com/quote/stock/NOVAVAX-INC-58256108/news/Novavax-EU-drugs-regulator-begins-rolling-review-of-Novavax-COVID-19-vaccine-32349124/