Food preservative peptide nisin can interact with SARS-CoV-2 spike protein receptor human ACE2

 RajarshiAayatti MallickGuptabSuranjitaMitraaSukhenduMandalcSwadesh R.Biswasa

DOI: https://doi.org/10.1016/j.virol.2020.10.002

Highlights

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A food grade natural peptide nisin can interact with the human ACE2 receptor.

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For the first time, we unraveled that a commonly used food preservative nisin can block ACE2 receptor.

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Binding affinity of nisin was higher than that of spike protein of SARS-CoV-2 as determined by docking studies.

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It was predicted that nisin competitively binds to the receptor over the spike protein.

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It could be an effective and safest therapeutic against COVID-19 infection.

Abstract

Nisin, a food-grade antimicrobial peptide produced by lactic acid bacteria has been examined for its probable interaction with the human ACE2 (hACE2) receptor, the site where spike protein of SARS-CoV-2 binds. Among the eight nisin variants examined, nisin H, nisin Z, nisin U and nisin A showed a significant binding affinity towards hACE2, higher than that of the RBD (receptor binding domain) of the SARS-CoV-2 spike protein. The molecular interaction of nisin with hACE2 was investigated by homology modeling and docking studies. Further, binding efficiency of the most potent nisin H was evaluated through the interaction of hACE2:nisin H complex with RBD (receptor-binding domain) of SARS-CoV-2 and that of hACE2:RBD complex with nisin H. Here, nisin H acted as a potential competitor of RBD to access the hACE2 receptor. The study unravels for the first time that a globally used food preservative, nisin has the potential to bind to hACE2.

https://www.sciencedirect.com/science/article/pii/S004268222030204X

Aptevo gets $50/share takeout offer from shareholder Tang

 

• Aptevo Therapeutics (NASDAQ:APVO) +35.7% after-hours following a disclosure that 42.5% shareholder Tang Capital Partners offered to buy the remaining shares for $50/share in cash.
• Shares have surged nearly 6x this month since announcing a complete remission in a Phase 1 clinical trial evaluating lead candidate APVO436 in patients with acute myeloid leukemia and myelodysplastic syndromes.
• Aptevo might be very close to being cash flow positive over the next 12 months, George Kesarios writes in a bullish analysis published recently on Seeking Alpha.
• https://seekingalpha.com/news/3637762-aptevo-gets-50-share-takeout-offer-from-shareholder-tang

It starts: Restaurant to require $50 on-site COVID-19 test for patrons

 It’s test-to-table dining.

A New York City restaurant will soon require all patrons to take a rapid coronavirus test at the door before being allowed to eat inside two days a week.

In what may be a first for Big Apple eateries, City Winery in the Meatpacking District will launch its pilot testing program on Tuesday.

“Given the change of the seasons, finding the next level of safety and comfort level for people to dine indoors is critical for us today,” Michael Dorf, the founder and CEO, said in a press release.

“A COVID-19 test is one of the only solutions to get patrons inside restaurants for the next five months until the springtime.”

Guests who want to visit the Pier 57 establishment on Tuesdays and Wednesdays will pre-pay $50 per person for the test when making a reservation via Resy online.

Upon arrival, a health professional will administer a nasal swab, and patrons will be able to sip on a glass of City Winery bubbly while they wait the 10 to 15 minutes for their results.

If the results are negative, the guests can go in — though they’ll still have to follow standard regulations such as wearing a mask and social distancing.

Should the test be positive, the venue will send the results to be verified by a lab — but the individual won’t be allowed in.

The eatery is still open test-free Thursday through Monday, and also offers outdoor dining.

https://nypost.com/2020/11/18/city-winery-will-require-50-on-site-covid-19-test-for-diners/

Chinese Covid Vaccine Gives Scientists Pause On Antibody Levels in Early Trials

 A leading Covid-19 vaccine under development in China showed inconclusive results about its level of protection, although scientists remain optimistic that the candidate can be among a roster of effective vaccines used to fight the pandemic.

In early-stage clinical trials, Sinovac Biotech Ltd.'s CoronaVac vaccine was shown to induce antibodies in the human body within 28 days of the first immunization, according to results published in the Lancet medical journal this week. The level of antibodies, however, were lower than that seen in people who were previously infected with Covid-19.

By contrast, the levels of antibodies in results from vaccine trials by Pfizer Inc. and Moderna Inc. were roughly on par with those in people who previously contracted the virus. This week, Pfizer said its experimental vaccine was 95% effective at protecting people from Covid-19, while Moderna said its vaccine was 94.5% effective based on an early look at late-stage results.

The results from Sinovac are for Phase 1 and Phase 2 clinical trials, which aren't designed to measure whether the vaccine works but can indicate whether it provokes an appropriate immune response. The firm hasn't published late-stage, or Phase 3, results, which measure efficacy.

"One would have liked the antibody levels to be comparable," said William Schaffner, professor of preventive medicine at Vanderbilt University School of Medicine. However, he said, the finding "may just mean the duration of protection may not be quite as long."

Scientists don't know what absolute level of antibody is needed to protect against the new coronavirus disease. It is possible that Sinovac's vaccine induces enough antibodies to confer protection.

The level of antibody often correlates with the duration of protection, although Dr. Schaffner said that Sinovac's results don't rule out its vaccine being able to protect people for a similar period of time as the Pfizer and Moderna vaccines.

China is behind four of nearly a dozen Covid-19 vaccines that are in the last phase of clinical trials, according to the World Health Organization, having recruited tens of thousands of volunteers around the world.

Scientists say the Chinese candidates may ultimately prove less effective than Western counterparts that use advanced gene-based technologies; the effective rates of more than 90% reported by Pfizer and Moderna surprised the scientific community, where many were hoping that the experimental Covid-19 vaccines would be at least 50% effective.

Both Sinovac and state-owned Sinopharm, the two leading Chinese vaccine developers, are using inactivated viruses for their vaccines. That technique involves growing viruses in a petri dish and then weakening them for vaccine purposes.

China has begun using vaccines by Sinovac and Sinopharm on hundreds of thousands of its citizens under an emergency-use program that started in July.

The Chinese drugmakers and government officials have declared the vaccines as safe to use, even as global public-health experts warn of the dangers of using vaccines so broadly and before clinical trial results are published.

Sinopharm has said that none of the 56,000 people who have received its vaccines, including Chinese workers overseas, have gotten infected. The firm's chairman, Liu Jingzhen, at a recent conference shared an example from an office of Huawei Technologies Co. in Mexico, where none of the 81 employees who were inoculated got infected; 10 employees who didn't get the vaccine ended up getting infected, he said.

The Huawei example didn't appear to be part of a clinical trial by Sinopharm, which is conducting formal studies in the United Arab Emirates, Bahrain, Egypt and other places.

Sinovac hasn't disclosed outcomes from people who have been inoculated with its vaccine and then traveled abroad.

Zhu Fengcai, who is an official at the Jiangsu province branch of the China Center for Disease Control and Prevention and a lead author of the Sinovac study laying out the result of the early-stage trials, said the quick antibody response the company's vaccine induced could make it suitable for emergency use. "However, further studies are needed to check how long the antibody response remains," he said.

Sinovac researcher Zeng Gang, another of the study's authors, said CoronaVac could be an attractive option because it can be stored in a standard refrigerator between 2 and 8 degrees Celsius, which is typical for flu vaccines. The Moderna and Pfizer vaccines need to be kept at a range of cold temperatures. Pfizer's must be stored at minus 70 degrees Celsius and then can be kept at standard refrigeration temperatures for about five days.

The Sinovac vaccine may also remain stable for up to three years in storage, which would offer some advantages for distribution to regions where access to refrigeration is challenging, Mr. Zeng added.

Sinovac conducted its early-stage trials in Jiangsu province. It is conducting late-stage clinical trials in Brazil, Indonesia and Turkey.

https://www.marketscreener.com/quote/stock/PFIZER-INC-23365019/news/Chinese-Covid-Vaccine-Gives-Scientists-Pause-Over-Antibody-Levels-in-Early-Trials-31814585/

Pfizer-BioNTech vaccine deliveries could start 'before Christmas'

 

Pfizer Inc and BioNTech could secure emergency U.S. and European authorization for their COVID-19 vaccine next month after final trial results showed it had a 95% success rate and no serious side effects, the drugmakers said on Wednesday.

The vaccine's efficacy was found to be consistent across different ages and ethnicities - a promising sign given the disease has disproportionately hurt the elderly and certain groups including Black people.

The U.S. Food and Drug Administration could grant emergency-use by the middle of December, BioNTech Chief Executive Ugur Sahin told Reuters TV. Conditional approval in the European Union could be secured in the second half of December, he added.

"If all goes well I could imagine that we gain approval in the second half of December and start deliveries before Christmas, but really only if all goes positively," he said.

The success rate of the vaccine developed by the U.S. drugmaker and German partner BioNTech was far higher than what regulators had said would have been acceptable. Experts said it was a significant achievement in the race to end the pandemic.

Of the 170 volunteers who contracted COVID-19 in Pfizer's trial involving over 43,000 people, 162 had received a placebo and not the vaccine, meaning the vaccine was 95% effective. Of the 10 people who had severe COVID-19, one had received the vaccine.

"A first in the history of mankind: less than a year from the sequence of the virus to the large-scale clinical trial of a vaccine, moreover based on a whole new technique," said Enrico Bucci, a biologist at Temple University in Philadelphia. "Today is a special day."

BioNTech's Sahin said U.S. emergency use authorization (EUA) would be applied for on Friday.

An FDA advisory committee tentatively plans to meet on Dec. 8-10 to discuss the vaccine, a source familiar with the situation said, though the dates could change. The FDA did not respond to requests for comment.

COVID-19 RUNS RAMPANT

The final trial analysis comes a week after initial results showed the vaccine was more than 90% effective. Moderna Inc on Monday released preliminary data for its vaccine showing 94.5% effectiveness.

"We now have two safe and highly effective vaccines that could be authorized by the Food and Drug Administration and ready to distribute within weeks," U.S. Health and Human Services Secretary Alex Azar said.

The Moderna vaccine is likely to be authorized within seven to 10 days of Pfizer receiving its EUA, U.S. officials said, with states ready to begin distribution within 24 hours.

The better-than-expected results from the two vaccines, both developed with new messenger RNA (mRNA) technology, have raised hopes for an end to a pandemic that has killed more than 1.3 million people and wreaked havoc upon economies and daily life.

The news was especially welcome with the virus again running rampant around the world, setting records for new infections and hospitalizations almost daily.

The Pfizer-BioNTech shot was found to have 94% efficacy in people over age 65, a particularly high-risk group.

"This is the evidence we needed to ensure that the most vulnerable people are protected," said Andrew Hill, senior visiting research fellow at the University of Liverpool's department of pharmacology.

Global shares rose as the trial results countered concerns around the soaring infection rate. Pfizer shares were up 1.6% while BioNTech jumped 3.8% in the United States. Moderna shares fell 3.6%. [MKTS/GLOB]

Investors have treated vaccine development as a race between companies, although there is likely to be global demand for as much vaccine as can be produced for the foreseeable future.

DISTRIBUTING SHOTS

Pfizer said it expects to make as many as 50 million vaccine doses this year, enough to protect 25 million people, and then produce up to 1.3 billion doses in 2021.

While some groups such as healthcare workers will be prioritized in the United States and Britain for vaccinations, it will be months before large-scale rollouts begin in either country.

On Wednesday, Pfizer said it had offered to provide Brazil with millions of doses in the first half of 2021. It also has agreements with the European Union, Germany and Japan where distribution could begin next year.

Mike Ryan, the World Health Organization's top emergency expert, said it would be at least 4-6 months before significant levels of vaccination were taking place around the world.

Distribution of a Pfizer-BioNTech shot is complicated by the need to store it at ultra-cold temperatures of -70 degrees Celsius. It can, however, be kept in normal refrigeration for up to five days, or up to 15 days in a thermal shipping box.

Moderna's vaccine can be stored for up to six months at -20C though it is expected to be stable for 30 days at normal fridge temperatures of 2 to 8 degrees Celsius (36°-46°F).

FATIGUE AND HEADACHES

Pfizer said vaccine was well-tolerated and that side effects were mostly mild to moderate, and cleared up quickly. The only severe adverse events experienced by volunteers were fatigue (3.8%) and headaches (2%) after the second dose. Older adults tended to report fewer and milder adverse events.

"These are extraordinary results, and the safety data look good," said David Spiegelhalter, a professor and expert in risk and evidence communication at the University of Cambridge.

Of the dozens of drugmakers and research groups racing to develop COVID-19 vaccines, the next late-stage data will likely be from AstraZeneca Plc with the University of Oxford in November or December. Johnson & Johnson said it is on track to deliver data this year.

Authorization of vaccines for children will take longer. Only Pfizer has started vaccinating volunteers under age 18 and as young as 12. Moderna and J&J have said they hope to start testing the vaccine in younger people soon.

https://www.marketscreener.com/quote/stock/ASTRAZENECA-PLC-4000930/news/AstraZeneca-Pfizer-BioNTech-vaccine-deliveries-could-start-before-Christmas-31810385/

FDA plans early Dec. meets on Covid vaccines ahead of possible OKs

The Food and Drug Administration has asked a group of advisors to set aside three days in early December for potential meetings to discuss Covid-19 vaccines — a key step in the agency’s authorization process, according to two people familiar with the plans.

The advisory group may be asked to weigh in on Pfizer and Moderna’s vaccines, said the people, who asked not to be named because the plans aren’t yet public.

The meetings, tentatively set for Dec. 8-10, would come just weeks after both companies reported data from their phase three trials showing their vaccines are about 95% effective in preventing cases of Covid-19.

Wednesday morning, Pfizer and its partner BioNTech reported final efficacy results from their study, saying they had reached the FDA’s required safety milestone and planned to submit their application to use the vaccine on an emergency basis within days.

Moderna is expected to pass that safety milestone imminently as well. The FDA requires two months of safety follow-up after half the participants in the trial have been fully vaccinated — receiving two shots of the vaccine a few weeks apart. The company said Monday it planned to seek the FDA’s authorization within weeks.

The regulator is expected to decide quickly on the vaccines after the meetings of the group, known as VRBPAC, for Vaccines and Related Biological Products Advisory Committee. If it gives the vaccines its green light, an advisory committee to the Centers for Disease Control and Prevention would make recommendations on prioritizatio

A spokeswoman for the FDA declined to comment on the meetings.

The CDC’s group, the Advisory Committee on Immunization Practices, or ACIP, scheduled a meeting for Nov. 23. That’s expected to be a preapproval meeting for Covid-19 vaccines.

https://www.cnbc.com/2020/11/18/fda-said-to-plan-early-december-advisory-meetings-on-covid-19-vaccines.html

Hospitals across US cancel elective procedures — again

As COVID-19 hotspots spring up across the country, hospitals must once again grapple with how to take care of those patients while keeping other services open safely. It's a repeat of what facilities went through in the pandemic's early days on U.S. shores this spring as hospitals struggle to secure enough staff and equipment.

Then, hospitals began having access to relief funding from Congress. But another bill, which lobbies have been calling for, does not seem imminent.

Elective procedures such as knee or hip replacements that often can be delayed are also the most lucrative for systems, with many facing major financial fallout after similar predicaments earlier this year. But most electives are necessary, just not emergencies.

At Mayo Clinic in Northwest Wisconsin, both the ICU and medical surgical units are full, a spokesperson said Monday. The system stopped scheduling elective care starting Oct. 31 in order to free up beds for COVID-19 patients.

Other Mayo Clinic locations in Wisconsin and Minnesota have also reduced elective care, though the system will remain open for trauma, emergency and urgent care needs, a spokesperson said.

Cleveland Clinic is seeing the highest numbers of patients with COVID-19 since the start of the pandemic and started rolling back elective procedures Wednesday, according to a statement.

It initially planned to postpone non-urgent surgical cases requiring an inpatient stay at most of its hospitals for Friday and Monday but extended those cases through this coming Friday. It will still perform outpatient surgeries as scheduled, along with urgent and emergent surgeries including heart, cancer and neurological cases.

And across the country in Idaho, St. Luke's Health System stopped scheduling elective procedures requiring an overnight hospital stay until Christmas, according to a statement.

St. Luke's Boise, Meridian, Magic Valley and Nampa medical centers canceled elective cases scheduled this week, though its hospitals in McCall, Wood River and Mountain Home will not cancel any currently scheduled elective procedures.

Procedures not requiring an overnight hospital stay will not be impacted, St. Luke's said.

When the virus first hit earlier this year, CMS, along with some state and local authorities, placed restrictions on elective procedures, mandating systems had a certain amount of personal protective equipment on hand before performing them.

When surges eased the agencies reeled those restrictions in, putting the power back in the hands of health systems — many facing steep financial losses and eager to take on backlogs.

But rising cases mean resources are once again strained — this time, nationwide.

Intermountain Healthcare is running out of staffed ICU beds but forging ahead with with non-COVID-19 care — including elective procedures — to help people with their routine health needs, CEO Marc Harrison said during a press conference Tuesday with other Utah business leaders.

While most joint replacements historically require an overnight stay, the 24-hospital system is performing half of the joint replacements in its St. George, Utah, locations as outpatient procedures to free up beds and staff, Harrison said.

Advocate Aurora Health, with hospitals in Wisconsin and Illinois, announced Tuesday it would scale back elective inpatient procedures by 50% at its sites — or more depending on local needs.

"This will help free up more staffing to provide the critical patient care needed during this time," the system said in a statement. "Future changes will depend on staffing and surge levels and will require constant adjustment."

Advocate Aurora will still offer urgent care services and said it would alert patients to any changes in scheduled elective procedures or screenings.

COVID-19 inpatient admissions routinely have lengths of stay two to three times longer than non-COVID-19 patients, and about 300 employees at Mayo Clinic in Northwest Wisconsin are on work restrictions due to novel coronavirus exposures, according to a spokesperson.

Demand for temporary healthcare staff is also on the rise again, similar to the beginning of the pandemic. Travel nurse staffing firm Aya Healthcare reported a 57% increase in demand for travel nurses Wednesday, and said open "crisis nursing" positions increased 291%.

"This means I don't have three, four or five weeks to wait. I need these people like yesterday in order to take care of the patients and the heads that are in my beds right now," April Hansen, EVP of workforce and clinical services at Aya, said.

Systems are individually planning how they'll restart electives when surges eventually wane.

Mayo's plan is based on a combination of data points including staff absences, sustained low test positivity rates and a COVID-19 inpatient census. As figures decrease, it will incrementally return to standard operations, a spokesperson said.

Cleveland Clinic will reevaluate scheduled surgical cases on an ongoing basis as the pandemic continues, and is closely monitoring supplies, including availability of PPE, beds and staff, a spokesperson said.

Healthcare leaders throughout the pandemic have chided a lack of transparency into the national supply chain for PPE especially, straining their efforts to treat both COVID-19 and non-COVID-19 patients.

Leaders with the American Hospital Association, American Medical Association and American Nurses Association sent a letter Tuesday to President Donald Trump imploring his administration work closely with President-elect Joe Biden's transition team to share critical information related to the pandemic.

They asked for "real-time data and information on the supply of therapeutics, testing supplies, personal protective equipment, ventilators, hospital bed capacity and workforce availability to plan for further deployment of the nation’s assets."

https://www.healthcaredive.com/news/hospitals-cancel-elective-procedures-once-again/589202/