Speeding new treatments

 A year into the COVID-19 pandemic, mass vaccinations have begun to raise the tantalizing prospect of herd immunity that eventually curtails or halts the spread of SARS-CoV-2. But what if herd immunity is never fully achieved -- or if the mutating virus gives rise to hyper-virulent variants that diminish the benefits of vaccination?

Those questions underscore the need for effective treatments for people who continue to fall ill with the coronavirus. While a few existing drugs show some benefit, there's a pressing need to find new therapeutics.

Led by The University of New Mexico's Tudor Oprea, MD, PhD, scientists have created a unique tool to help drug researchers quickly identify molecules capable of disarming the virus before it invades human cells or disabling it in the early stages of the infection.

In a paper published this week in Nature Machine Intelligence, the researchers introduced REDIAL-2020, an open source online suite of computational models that will help scientists rapidly screen small molecules for their potential COVID-fighting properties.

"To some extent this replaces (laboratory) experiments, says Oprea, chief of the Translational Informatics Division in the UNM School of Medicine. "It narrows the field of what people need to focus on. That's why we placed it online for everyone to use."

Oprea's team at UNM and another group at the University of Texas at El Paso led by Suman Sirimulla, PhD, started work on the REDIAL-2020 tool last spring after scientists at the National Center for Advancing Translational Sciences (NCATS) released data from their own COVID drug repurposing studies.

"Becoming aware of this, I was like, 'Wait a minute, there's enough data here for us to build solid machine learning models,'" Oprea says. The results from NCATS laboratory assays gauged each molecule's ability to inhibit viral entry, infectivity and reproduction, such as the cytopathic effect -- the ability to protect a cell from being killed by the virus.

Biomedicine researchers often tend to focus on the positive findings from their studies, but in this case, the NCATS scientists also reported which molecules had no virus-fighting effects. The inclusion of negative data actually enhances the accuracy of machine learning, Oprea says.

"The idea was that we identify molecules that fit the perfect profile," he says. "You want to find molecules that do all these things and don't do the things that we don't want them to do."

The coronavirus is a wily adversary, Oprea says. "I don't think there is a drug that will fit everything to a T." Instead, researchers will likely devise a multi-drug cocktail that attacks the virus on multiple fronts. "It goes back to the one-two punch," he says.

REDIAL-2020 is based on machine learning algorithms capable of rapidly processing huge amounts of data and teasing out hidden patterns that might not be perceivable by a human researcher. Oprea's team validated the machine learning predictions based on the NCATS data by comparing them against the known effects of approved drugs in UNM's DrugCentral database.

In principle, this computational workflow is flexible and could be trained to evaluate compounds against other pathogens, as well as evaluate chemicals that have not yet been approved for human use, Oprea says.

"Our main intent remains drug repurposing, but we're actually focusing on any small molecule," he says. "It doesn't have to be an approved drug. Anyone who tests their molecule could come up with something important."

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Story Source:

Materials provided by University of New Mexico Health Sciences Center. Original written by Michael Haederle. Note: Content may be edited for style and length.

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Journal Reference:

1. Govinda B. KC, Giovanni Bocci, Srijan Verma, Md Mahmudulla Hassan, Jayme Holmes, Jeremy J. Yang, Suman Sirimulla, Tudor I. Oprea. A machine learning platform to estimate anti-SARS-CoV-2 activities. Nature Machine Intelligence, 2021; DOI: 10.1038/s42256-021-00335-w

https://www.sciencedaily.com/releases/2021/05/210503172844.htm

Shortage of DNA building blocks in the cell releases mitochondrial DNA

 Mitochondria are the energy suppliers of our body cells. These tiny cell components have their own genetic material, which triggers an inflammatory response when released into the interior of the cell. The reasons for the release are not yet known, but some cardiac and neurodegenerative diseases as well as the ageing process are linked to the mitochondrial genome. Researchers at the Max Planck Institute for Biology of Ageing and the CECAD Cluster of Excellence in Ageing research have investigated the reasons for the release of mitochondrial genetic material and found a direct link to cellular metabolism: when the cell's DNA building blocks are in short supply, mitochondria release their genetic material and trigger inflammation. The researchers hope to find new therapeutic approaches by influencing this metabolic pathway.

Our body needs energy -- for every metabolic process, every movement and for breathing. This energy is produced in tiny components of our body cells, the so-called mitochondria. Unlike other cell components, mitochondria have their own genetic material, mitochondrial DNA. However, in certain situations, mitochondria release their DNA into the interior of the cell, causing a reaction from the cell's own immune system and being associated with various diseases as well as the ageing process. The reasons for the release of mitochondrial DNA are not yet known.

Shortage of DNA building blocks triggers inflammatory reaction

To answer the question of when mitochondria release their DNA, researchers at the Max Planck Institute for Biology of Ageing have focused on the mitochondrial protein YME1L, which owes its name to yeast mutants that release their mitochondrial DNA -- yeast mitochondrial escape 1. "In cells lacking YME1L, we observed the release of mitochondrial DNA into the cell interior and a related immune response in the cells," said Thomas MacVicar, one of the study's two first authors. Closer examination revealed a direct link to the building blocks of DNA. "If the cells lack YME1L, there is a deficiency of DNA building blocks inside the cell," Thomas MacVicar describes. "This deficiency triggers the release of mitochondrial DNA, which in turn causes an inflammatory response in the cell: the cell stimulates similar inflammatory reactions as it does during a bacterial or viral infection. If we add DNA building blocks to the cells from the outside, that also stops the inflammation."

New therapeutic approaches based on the metabolism of DNA building blocks

The discovered link between the cellular inflammatory response and the metabolism of DNA building blocks could have far-reaching consequences, explains Thomas MacVicar: "Some viral inhibitors stop the production of certain DNA building blocks, thereby triggering an inflammatory response. The release of mitochondrial DNA could be a crucial factor in this, contributing to the effect of these inhibitors." Several ageing-associated inflammatory diseases, including cardiac and neurodegenerative diseases, as well as obesity and cancer, are linked to mitochondrial DNA. The authors hope that modulating the metabolism of DNA building blocks will offer new therapeutic opportunities in such diseases.

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Story Source:

Materials provided by Max-Planck-Gesellschaft. Note: Content may be edited for style and length.

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Journal Reference:

1. Hans-Georg Sprenger, Thomas MacVicar, Amir Bahat, Kai Uwe Fiedler, Steffen Hermans, Denise Ehrentraut, Katharina Ried, Dusanka Milenkovic, Nina Bonekamp, Nils-Göran Larsson, Hendrik Nolte, Patrick Giavalisco, Thomas Langer. Cellular pyrimidine imbalance triggers mitochondrial DNA–dependent innate immunity. Nature Metabolism, 2021; DOI: 10.1038/s42255-021-00385-9

https://www.sciencedaily.com/releases/2021/04/210430120346.htm

Human organ chips enable COVID-19 drug repurposing

 A Wyss Institute-led collaboration spanning four research labs and hundreds of miles has used the Institute's organ-on-a-chip (Organ Chip) technology to identify the antimalarial drug amodiaquine as a potent inhibitor of infection with SARS-CoV-2, the virus that causes COVID-19.

The Organ Chip-based drug testing ecosystem established by the collaboration greatly streamlines the process of evaluating the safety and efficacy of existing drugs for new medical applications, and provides a proof-of-concept for the use of Organ Chips to rapidly repurpose existing drugs for new medical applications, including future pandemics. The research is reported in Nature Biomedical Engineering.

While many groups around the world have been testing existing drugs for efficacy against COVID-19 using cultured cells, it is well known that cells grown in a dish do not behave like the cells in a living human body, and many drugs that appear effective in lab studies do not work in patients. The Wyss team examined eight existing drugs, including hydroxychloroquine and chloroquine, that they and others had found were active against SARS-CoV-2 in conventional cell culture assays.

When tested in their more sophisticated microfluidic Lung Airway Chip, which had been infected with a pseudotyped SARS-CoV-2 virus, they found that most of these drugs, including hydroxychloroquine and chloroquine, were not effective. However, another antimalarial drug, amodiaquine, was highly effective at preventing viral entry. These results were then validated in cultured cells and in a small animal model of COVID-19 using infectious SARS-CoV-2 virus. Amodiaquine is now in clinical trials for COVID-19 at multiple sites in Africa, where this drug is inexpensive and widely available.

"The speed with which this team assembled, pivoted to COVID-19, and produced clinically significant results is astonishing," said senior author and Wyss Institute Founding Director Don Ingber, M.D., Ph.D. "We started testing these compounds in February 2020, had data by March, and published a preprint in April. Thanks to the openness and collaboration that the pandemic has sparked within the scientific community, our lead drug is now being tested in humans. It's a powerful testament to Organ Chips' ability to accelerate preclinical testing."

From mysterious disease to lead compound in months

In the early months of the COVID-19 pandemic when little was known about the novel SARS-CoV-2 virus, efforts were made around the globe to identify existing drugs that could be repurposed to treat patients who were falling ill. While early data performed on cells grown in lab dishes seemed to suggest that the antimalarial drugs chloroquine and hydroxychloroquine could treat the disease, later studies showed that they aren't active against SARS-CoV-2 in animals or patients, and the quest for an effective oral therapeutic that can both treat and prevent COVID-19 continues.

Fortunately, the Wyss Institute had a ready-made solution to that problem. In a move that today seems prescient, over three years ago the Defense Advanced Research Projects Agency (DARPA) and National Institutes of Health (NIH) awarded funding to Ingber's team to explore whether its human Organ Chip microfluidic culture technology, which faithfully mimics the function of human organs in vitro, could be used to confront potential biothreat challenges including pandemic respiratory viruses.

Two years into the project, the team was making steady progress using its lung Airway Chip to study drugs that could be repurposed to treat influenza virus infections. Then, in January 2020, first authors Longlong Si, Ph.D. and Haiqing Bai, Ph.D. heard about cases of what was being called a novel viral pneumonia in China.

"That caught a lot of scientists' attention, because any new virus could become a global threat given how easily infections spread in today's era of widespread international travel. We closely followed the updates because we thought that our Airway Chip model could provide an important tool for studying this virus," said Si, a Wyss Technology Development Fellow and co-lead author. Once it became clear that people were falling ill due to the mysterious COVID-19 and not pneumonia, the team quickly shifted its focus to the novel SARS-CoV-2 virus.

The human Airway Chip that the Wyss team developed for these studies is a microfluidic device about the size of a USB memory stick that contains two parallel channels separated by a porous membrane. Human lung airway cells are grown in one channel that is perfused with air, while human blood vessel cells are grown in the other channel, which is perfused with liquid culture medium to mimic blood flow. Cells grown in this device naturally differentiate into multiple airway-specific cell types in proportions that are similar to those in the human airway, and develop traits observed in living lungs such as cilia and the ability to produce and move mucus. Airway Chip cells also have higher levels of angiotensin-converting enzyme-2 (ACE2) receptor protein, which plays a central role in lung physiology and is used by SARS-CoV-2 to infect cells.

"Our biggest challenge in shifting our focus to SARS-CoV-2 was that we don't have lab facilities with the necessary infrastructure to safely study dangerous pathogens. To get around that problem, we designed a SARS-CoV-2 pseudovirus that expresses the SARS-CoV-2 spike protein, so that we could identify drugs that interfere with the spike protein's ability to bind to human lung cells' ACE2 receptors," said Bai, who is a Postdoctoral Fellow at the Wyss Institute and co-lead author. "A secondary goal was to demonstrate that these types of studies could be carried out by other Organ Chip researchers who similarly have this technology, but lack access to lab facilities required to study highly infectious viruses."

Armed with the pseudovirus that allowed them to study SARS-CoV-2 infection, the team first perfused the Airway Chips' blood vessel channel with several approved drugs, including amodiaquine, toremifene, clomiphene, chloroquine, hydroxychloroquine, arbidol, verapamil, and amiodarone, all of which have exhibited activity against other related viruses in previous studies. However, in contrast to static culture studies, they were able to perfuse the drug through the channels of the chip using a clinically relevant dose to mimic how the drug would be distributed to tissues in our bodies. After 24 hours they introduced SARS-CoV-2 pseudovirus into the Airway Chips' air channel to mimic infection by airborne viruses, like that in a cough or sneeze.

Only three of these drugs ? amodiaquine, toremifene, and clomiphene ? significantly prevented viral entry without producing cell damage in the Airway Chips. The most potent drug, amodiaquine, reduced infection by about 60%. The team also performed spectrometry measurements with the assistance of Steve Gygi, Ph.D.'s group at Harvard Medical School to assess how the drugs impacted the airway cells. These studies revealed that amodiaquine produced distinct and broader protein changes than the other antimalarial drugs.

The researchers had a lead drug candidate.

All hands on deck

Despite the promise of amodiaquine, the team still needed to demonstrate that it worked against the real infectious SARS-CoV-2 virus. With the help of a new COVID-19-focused grant from DARPA, Ingber teamed up with Matthew Frieman, Ph.D. at the University of Maryland School of Medicin and Benjamin tenOever, Ph.D. at the Icahn School of Medicine at Mount Sinai, both of whom already had biosafety labs set up to study infectious pathogens.

This collaboration created a drug discovery ecosystem that combines the human emulation capability of the Wyss Institute's Organ Chips with Frieman's and tenOever's expertise in the interactions between viruses and their host cells. The Frieman lab tested amodiaquine and its active metabolite, desethylamodiaquine, against native SARS-CoV-2 via high-throughput assays in cells in vitro, and confirmed that the drug inhibited viral infection.

In parallel, the tenOever lab tested amodiaquine and hydroxychloroquine against native SARS-CoV-2 in a head-to-head comparison in a small animal COVID-19 model, and saw that prophylactic treatment with amodiaquine resulted in ~70% reduction in viral load upon exposure, while hydroxychloroquine was ineffective. They also saw that amodiaquine prevented the transmission of the virus from sick to healthy animals more than 90% of the time, and that it was also effective in reducing viral load when administered after introduction of the virus. Thus, their results suggest that amodiaquine could work in both treatment and prevention modes.

"Seeing how beautifully amodiaquine inhibited infection in the Airway Chip was extremely exciting," said Frieman. "And, the fact that it seems to work both before and after exposure to SARS-CoV-2 means that it could potentially be effective in a wide variety of settings."

"This collaboration has allowed us to do things that we never would have had the resources to do otherwise, including recently setting up Organ Chips in our own lab so that we can now use them to study the interactions between infectious viruses and their hosts. While we're proud of what we've accomplished so far for COVID-19, we're also looking forward to studying additional virus-host dynamics using the Organ Chips in the hopes that we'll be able to prevent or address future pandemics," said tenOever, who is a Professor of Microbiology.

A preprint of the amodiaquine results was published online on April 15, 2020, which generated buzz in the scientific community. It eventually caught the eye of Medicines for Malaria Venture, a leading product development partnership in antimalarial drug research. These results, along with studies from several other groups, contributed to amodiaquine's inclusion in a clinical trial in collaboration with the University of Witwatersrand in South Africa and Shin Poong Pharmaceutical in South Korea last fall. A few months later, the Drugs for Neglected Diseases Initiative (DNDi) added amodiaquine to the ANTICOV clinical trial for COVID-19, which spans 19 sites in over 13 different countries in Africa. Amodiaquine is oral, extremely inexpensive, and widely available in Africa. If proven effective in these clinical trials, it could provide a badly needed weapon against COVID-19 in low-resource nations where access to vaccines and expensive new therapeutics is limited.

Preparing for the next pandemic

While the identification of amodiaquine is a major boon in fighting COVID-19, the team already has their sights set on future pandemics. In addition to SARS-CoV-2, their recent publication details their success in finding drugs that could protect against or treat several strains of influenza virus.

"Thanks to our experience using this drug development pipeline to validate amodiaquine for COVID-19, we are now applying what we learned to influenza and other pandemic-causing pathogens," said co-author Ken Carlson, Ph.D., a Lead Senior Staff Scientist who helps lead the Coronavirus Therapeutic Project Team at the Wyss Institute. "This process has given us confidence that Organ Chips are predictive of what we see in more complex living models of viral infections, and helped harness the creative cauldron of the Wyss Institute to consolidate and strengthen our therapeutic discovery engine."

In addition to influenza, the team is now exploring drugs that could be used against the new SARS-CoV-2 mutant strains, to suppress the dangerous "cytokine storm" that leads to many hospitalizations, and to relieve the symptoms of COVID-19 "long haulers."

"The pandemic has really gelled the Wyss Institute's Bioinspired Therapeutics development program, and linking up with the Frieman and tenOever labs has created a drug discovery and development pipeline that dramatically speeds up the whole process, quickly shepherding COVID-19 drugs through preclinical development to the point where they can be tested in humans. With Organ Chip technology in hand, we are now in a stronger position to confront future pandemics," said Ingber, who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children's Hospital, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.

Additional authors of the paper include Melissa Rodas, Wuji Cao, Crystal Oh, Mercy Soong, Atiq Nurani, Seong Min Kim, Danni Zhu, Girija Goyal, Rani Powers, and Roberto Plebiani from the Wyss Institute; former Wyss Institute members Rachelle Prantil-Baun, Kambez Benam, and Sarah Gilpin; Amanda Jiang from Boston Children's Hospital and Harvard Medical School; Rasmus Moller, Daisy Hoagland, Kohei Oishi, Shu Horiuchi, Skyler Uhl, Daniel Blanco-Melo, Tristan Jordan, Benjamin Nilsson-Payant, Ilona Golynker, and Justin Frere from the Icahn School of Medicine at Mount Sinai; James Logue, Robert Haupt, Marisa McGrath, and Stuart Weston from the University of Maryland School of Medicine; Tian Zhang and Steve Gygi from Harvard Medical School;

This research was supported by the NIH (NCATS 1-UG3-HL-141797-01 and NCATS 1-UH3-HL- 141797-01), DARPA (W911NF-12-2-0036 and W911NF-16-C-0050), the Bill and Melinda Gates Foundation, the Marc Haas Foundation, and the Wyss Institute for Biologically Inspired Engineering at Harvard University.

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Story Source:

Materials provided by Wyss Institute for Biologically Inspired Engineering at Harvard. Original written by Lindsay Brownell. Note: Content may be edited for style and length.

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Journal Reference:

1. Longlong Si, Haiqing Bai, Melissa Rodas, Wuji Cao, Crystal Yuri Oh, Amanda Jiang, Rasmus Moller, Daisy Hoagland, Kohei Oishi, Shu Horiuchi, Skyler Uhl, Daniel Blanco-Melo, Randy A. Albrecht, Wen-Chun Liu, Tristan Jordan, Benjamin E. Nilsson-Payant, Ilona Golynker, Justin Frere, James Logue, Robert Haupt, Marisa McGrath, Stuart Weston, Tian Zhang, Roberto Plebani, Mercy Soong, Atiq Nurani, Seong Min Kim, Danni Y. Zhu, Kambez H. Benam, Girija Goyal, Sarah E. Gilpin, Rachelle Prantil-Baun, Steven P. Gygi, Rani K. Powers, Kenneth E. Carlson, Matthew Frieman, Benjamin R. tenOever, Donald E. Ingber. A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics. Nature Biomedical Engineering, 2021; DOI: 10.1038/s41551-021-00718-9

https://www.sciencedaily.com/releases/2021/05/210503144724.htm

Astellas Walks Away From $450M Partnership With Cytokinetics

 

• Cytokinetics Inc (NASDAQ: CYTK) revealed in an SEC filing that Astellas Pharma Inc (OTCMKTS: ALPMY) is walking away from a pact to research and develop skeletal sarcomere activators for diseases associated with muscle weakness.

• Astellas had extended the research pact initially set to expire on December 31 last year, through March of this year.

• But last week, Astellas gave written notice that it wants out of the pact altogether and gives up “all licenses and other rights” granted through the pact.

• In 2013, Astellas had initially signed up to get exclusive rights to co-develop and sell skeletal sarcomere activators in all indications.

• In turn, Cytokinetics had the right to co-promote and do some sales work in the U.S., Canada, and Europe.

• Should these drugs have been taken forward solely by Astellas, Cytokinetics could have received over $450 million in pre-commercialization and commercialization milestones plus royalties.

• No reason was given for the breakup, which will be official this November 1, nor updates on the programs. Cytokinetics is set to release its financials later this week.

• It comes two years after Cytokinetics’ reldesemtiv missed the primary endpoint in phase 2 amyotrophic lateral sclerosis trial. The Astellas-partnered drug failed to beat placebo on a lung function test in May 2019.

• It also comes a few months after Amgen Inc (NASDAQ: AMGN) culled its pact with Cytokinetics for heart failure omecamtiv mecarbil after unimpressive Phase 3 data.

https://finance.yahoo.com/news/astellas-walks-away-450m-research-184846778.html

Effect of COVID-19 on Breast Cancer Treatment Examined

 More patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2-negative breast cancer have been treated with neoadjuvant endocrine therapy (NET) due to COVID-19, according to a study presented at the annual meeting of the American Society of Breast Surgeons, held virtually from April 29 to May 2.

Lee G. Wilke, M.D., from the University of Wisconsin School of Medicine and Public Health in Madison, and colleagues report on the initial impact of the COVID-19 pandemic on breast cancer using data for a COVID-19-specific registry, developed within the American Society of Breast Surgeons Mastery program. A total of 172 surgeons entered data on 2,476 unique COVID-19 registry and 2,303 Mastery registry patients between March 1 and Oct. 28, 2020.

The researchers found that for patients with ER-positive, human epidermal growth factor receptor 2-negative disease, NET was used as a "usual" approach in 6.5 percent of patients in the COVID-19 registry, which was comparable to the 7.8 percent in the Mastery. In an additional 36 percent of patients, NET was used due to COVID-19. Patients were more likely to receive NET due to COVID-19 with increasing age and if they lived in the North or Southeast in a multinomial regression with surgery first/usual practice as the reference (odds ratios, 1.1, 2.2, and 1.6, respectively). Overall, 10.8 percent of patients had a change in surgical approach reported due to COVID-19, with the primary reasons being planned return for mastectomy or reconstruction (27 and 15 percent, respectively).

"COVID-related breast cancer treatment changes may have provided the context for testing new protocols, with some likely to persist beyond the pandemic," Wilke said in a statement.

https://consumer.healthday.com/asbrs-effect-of-covid-19-on-breast-cancer-treatment-examined-2652791966.html

6 States Ban COVID-19 Vaccine Requirements

 As COVID-19 vaccinations continue across the country, Arkansas and Montana are the latest states to advance legislation or enact laws that ban certain requirements – such as vaccine passports or conditions of employment – based on inoculation status.

Arkansas Gov. Asa Hutchinson, a Republican, on April 28 signed into law various measures that prevent state and local governments from requiring proof of vaccination as a condition of employment or to access goods and services, according to The Associated Press. The ban on requirements related to employment has some exceptions, including state-owned medical facilities.

The measure related to goods and services access is tied to the concept of "vaccine passports," which provide proof of vaccination for activities such as traveling or attending concerts. Governors in six states – Arizona, Florida, Idaho, Montana, Texas and South Dakota – "have issued executive orders prohibiting vaccine passports/requirements in some regard," according to James Nash, press secretary for the National Governors Association. Officials in the Joe Biden administration, however, have insisted that there aren't plans for a federal vaccine passport system.

"Let me be clear that the government is not now, nor will we be supporting a system that requires Americans to carry a credential," said Jeff Zients, the White House COVID-19 response coordinator, during an April 14 press briefing. "There'll be no federal vaccination database, no federal mandate requiring everyone to obtain a single vaccination credential."

Despite this commitment from federal officials, Montana's Republican Gov. Greg Gianforte on April 13 issued an executive order banning the "state-sponsored development and required use of so-called vaccine passports." The state is also close to enacting legislation advanced by its state Legislature that would prohibit employers from requiring vaccinations as a condition of employment.

The bill "makes it an unlawful discriminatory practice for a person or governmental entity to deny services, goods, privileges, licensing, educational opportunities or employment opportunities based on vaccination status or whether someone has an immunity passport," according to the AP. But after being advanced to Gianforte for his signature, the bill was sent back by the governor with an amendment that exempts nursing homes and long-term care facilities from the measure's provisions and allows health care facilities "to ask employees to volunteer information about their vaccination status, to consider employees who don't volunteer that information to be unvaccinated, and to implement policies specific to unvaccinated staff, patients and visitors that are designed to protect against the spread of communicable diseases," according to the Montana Free Press. Both the state's House and Senate later approved the amended bill, clearing the way for Gianforte's final signature, the outlet reported.

Attempts to ban COVID-19 vaccine requirements are common among states. Overall, at least 32 bills have been introduced across 25 states that "would limit mandatory COVID-19 vaccines for students, employees or generally," according to a recent memo from the National Conference of State Legislatures.

Most of the measures are pending and some – including bills in Virginia and Wyoming – have failed, but one will soon become law in Utah. Starting on May 5, the state Legislature's House Bill 308, similar to the legislation in Arkansas and Montana, will prohibit "a government entity from directly or indirectly requiring an individual to receive a COVID-19 vaccine authorized for emergency use as a condition of employment or attendance at events that are hosted or sponsored by a government entity," according to the NCSL.

Bills in a handful of states – such as Alabama, Minnesota and South Carolina – refer to a so-called COVID-19 Vaccine Bill of Rights, which "prohibits mandatory COVID-19 vaccinations and prohibits businesses from requiring any person to receive COVID-19 vaccines," the NCSL also found. Several other states have introduced legislation that aims to "prohibit mandatory vaccines generally," says Mick Bullock, the public affairs director for the National Conference of State Legislatures.

But some states are going the other way on COVID-19 vaccine requirements. At least two – Hawaii and New York – have considered legislation "that would support or allow the use of coronavirus vaccine records or 'passports' in some capacity," according to the NCSL. Hawaii Gov. David Ige, a Democrat, on April 20 unveiled a program that allows individuals who have been fully vaccinated in the state to bypass pre-travel testing and/or quarantine requirements when traveling within the state, according to a news release. Hawaii's state Legislature previously considered a similar measure, according to the NCSL.

Inoculation against COVID-19 continues to ramp up across America. As of April 28, at least 43% of the population have received at least one dose of the vaccine, according to U.S. Centers for Disease Control and Prevention data compiled and analyzed by USAFacts. The CDC later reported on Thursday that 30% of the U.S. population is now fully vaccinated.

https://www.usnews.com/news/best-states/articles/2021-04-30/these-states-are-banning-covid-19-vaccine-requirements

U.S. to start talks with WTO over lifting COVID-19 vaccine patents

 The Biden administration said it will begin talks this week with the World Trade Organization about lifting intellectual property rights for coronavirus vaccines as activists and foreign leaders urge the move for the benefit of poorer nations.

White House Chief of Staff Ron Klain told CBS's Face the Nation in an interview Sunday that Katherine Tai, the United States' top trade negotiator, will head to the WTO to open talks on "how we can get this vaccine more widely distributed, more widely licensed, more widely shared."

The announcement was made as pressure from activists, progressive politicians and foreign leaders mounts on the White House to support waiving pharmaceutical patents on vaccine production to allow poorer countries to make their own versions of the shot.

Early last week, Indian Prime Minister Narendra Modi told President Joe Biden in a phone call about a motion it brought before the WTO along with South Africa to waive certain trade provisions concerning vaccines, according to a readout of the call from Modi's office.

The motion calls for the waiver to be in place "until widespread vaccination is in place globally, and the majority of the world's population has developed immunity."

The call between the two heads of state was made as India battles another surge in cases. In the last two days, Indian health officials have reported some 800,000 infections and more than 7,000 deaths.

In mid-April, more than 170 heads of states and Nobel laureates, including Kim Campbell, the former prime minister of Canada, and former British Prime Minister Gordon Brown, called on Biden to support the motion.

"A WTO waiver is a vital and necessary step to bringing an end to this pandemic," the leaders said in a letter sent to the president by The People's Vaccine movement. "With your leadership, we can ensure COVID-19 vaccine technology is shared with the world."

At the current rate of immunization in poorer nations, many will be waiting until at least 2024 to get the shot, they said.

In March, World Health Director-General Tedros Adhanom Ghebreyesus also called for patents to be waived to put the world "on a war footing."

"I don't believe that globally we're exercising our full manufacturing muscle at present," he said. "Let's not be held back by politics, business as usual or those that say we can't."

Klain said Sunday that intellectual property rights are only part of the problem with manufacturing being more to blame for vaccine supply issues.

India has a domestic vaccine called Covishield and production there has slowed due to a lack of raw materials, he said, adding the United States has sent enough to make some 20 million does as the country battles another surge in cases.

"Manufacturing is the biggest problem," he said. "We have a factory here in the U.S. that has the full intellectual property rights to make the vaccine. They aren't making doses because the factory has problems."

https://www.upi.com/Top_News/US/2021/05/03/United-States-start-coronavirus-vaccine-patent-talks-World-Trade-Organization/1691620027178/