It’s possible that I shall make an ass of myself. But in that case one can always get out of it with a little dialectic. I have, of course, so worded my proposition as to be right either way (K.Marx, Letter to F.Engels on the Indian Mutiny)
Russian forces appear to have used an unmanned surface vessel (USV) to attack a strategic bridge between Ukraine and Moldova, according to social media reports and defense analysts. It represents the first known Russian use of a USV in combat, though not the first use in the Black Sea.
The Zatoka road and rail bridge connects the Ukrainian port of Odessa with Moldova. It is the only road and rail link between the two nations. The bridge was hit previously by a Russian cruise missile strike in 2022, and photos from the missile attack have circulated again on social media, purporting to show the aftermath of Friday's drone strike. The extent of any damage from the drone boat attack was not immediately clear.
Ukraine's top military officer, Gen. Valery Zaluzhny, appeared to confirm the attack in a statement on Saturday. In a readout of a recent telephone call with U.S. Chairman of the Joint Chiefs of Staff Gen. Mark Milley, Gen. Zaluzhny noted his concern over "Russia's use of maritime surface drones, which pose a threat to civilian shipping in the Black Sea."
In October, Ukraine used unmanned surface vessels armed with explosive warheads to attack the Russian Black Sea Fleet. The strike may have resulted in a successful hit on the frigate Admiral Makarov, the current flagship of the Black Sea Fleet. Russia's Ministry of Defense claimed that eight unmanned aerial vehicles and seven unmanned surface vessels (USVs) were involved in the attack, and reported that the minesweeper Ivan Golubets sustained "minor damage."
After the Ukrainian attack, Russia withdrew the majority of its vessel assets to Novorossyisk, further away from Ukrainian shores. It also emplaced multiple floating barriers between its warship berths and the harbor entrance in order to thwart small-craft attacks. Analysts were quick to note that similar low-tech barriers would go a long ways towards warding off future attacks at Ukraine's fixed targets, like the Zakota bridge.
Though Russia has not previously announced a drone-boat development program, Russian forces captured a similar Ukrainian drone on the beach near Sevastopol in September, and would have had the opportunity to examine it. Russia also has extensive engineering capabilities of its own, along with access to technical assistance from the Iranian military, which has experience in the development of explosives-laden drone boats.
Euronav Loses First Arbitration as Frontline and CMB Reject Compromise
Euronav continues to find itself caught between its two large shareholders (Euronav file photo)
The struggle over the future of tanker operator Euronav continues to play out between the boardroom and the courts. The company continues to find itself caught between its two large shareholders, CMB and Frontline, each of which controls approximately a quarter of the shares outstanding and shows no signs of a compromise.
Frontline has won the first step in its fight against Euronav after announcing early in January 2023 that it had decided not to proceed with the share exchange as a first step toward combining the two companies. At the time, Frontline said it had determined that the combination would not realize the anticipated outcome due to the ongoing opposition of CMB and the Saverys family, which had said it would block completing the merger of the two companies.
Euronav sought an emergency arbitration to prevent Frontline from walking away from the agreements. Today, February 7, the companies reported that the judge rejected the petition for an interim and provisional measure to stop Frontline from abandoning the deal. Frontline said the claims were fully dismissed noting that the arbitrator ordered Euronav to pay its legal costs.
“This decision strengthens Frontline’s position that its decision to terminate the combination agreement was entirely lawful,” the tanker company controlled by John Fredriksen said in its announcement. Frontline however is not yet entirely free from its obligations as Euronav filed for a second phase of the arbitration on January 28 that will consider the full merits of the claim. Euronav contends the emergency arbitration was dismissed because of a lack of urgency to its claim with the arbitrator preferring to let it proceed to a hearing on the full combination agreement.
Euronav also reports that the warring shareholders refused its proposal for shared oversight of the company. Euronav had proposed reconstituting the supervisory board with two representatives, Marc Saverys and Patrick De Brabandere, from CMB and two from Fredriksen’s organization, while also maintaining continuity. They said that CMB had informed them it was “not inclined to agree.”
After the announcement that the combination would not proceed, CMB renewed its pressure on the supervisory board. Under Belgian security law, they requested a Special General Meeting of the shareholders proposing to replace the entire supervisory board with Marc Saverys and a slate of directors selected by the family.
Euronav has set March 23 as the date for the shareholder meeting to consider the proposal from CMB. With Frontline and CMB currently each holding nearly equal positions in the stock, the institutional shareholders will decide on the issues including the current board versus the Saverys. The proposal is part of the family’s belief that Euronav should be moving in new directions to address the challenges to decarbonize the operations and the longer-term prospects for the oil markets.
Near term, however, the markets are strong with Euronav predicting during last week’s financial report “positive conditions within the tanker market for multiple quarters ahead.” They pointed at their efforts in positioning in the market including fleet renewal saying with demand driving freight rates to a 30-month high they believed they were well positioned to participate in the continuing market upcycle.
Crowley Locks In Option to Build a Wind Terminal at Port Fourchon
Staying a step ahead of the U.S. offshore wind industry's next phase of development, Crowley has reached a deal with Port Fourchon for right of first refusal to build an offshore wind terminal on Louisiana's coast.
Port Fourchon has a 40-acre site with 2,200 feet of waterfront that might well become an offshore wind terminal in the years ahead, according to Crowley. Interest in the Gulf of Mexico's wind potential is picking up, and the U.S. Bureau of Ocean Energy Management has designated its first two Wind Energy Areas (WEAs) in the region - including one located off Lake Charles, about 150 nm to the west of Port Fourchon.
BOEM's initial call for expressions of interest in wind power development extended well to the east along the Louisiana coast, including possible areas nearer to Fourchon. There may be additional opportunities closer to shore: utility Entergy is working with Japanese-owned Diamond Offshore Wind to examine early-stage development opportunities in state waters.
The designated Wind Energy Area (WEA) off Lake Charles (Illustration courtesy BOEM)
“We are thrilled to take the next step to welcome Crowley to Port Fourchon and our amazing slate of tenants and users,” said Chett Chiasson, executive director of the Greater Lafourche Port Commission. “Crowley’s forward-thinking vision aligns perfectly with our goals at the GLPC to further our role as a leading service supply port for all forms of energy, including wind.”
Crowley has moved quickly to secure its place in the future offshore wind market. It is planning a wind terminal project at Eureka, California, where it recently signed a develop/operate agreement with the Port of Humboldt Bay; and it has announced plans to begin building a terminal this summer at the port of Salem in Massachusetts. where it recently bought a 40-acre parcel of land to support Avangrid's Commonwealth Wind project.
In addition to terminal and logistics services, Crowley's Wind Services division is working with offshore vessel operator Esvagt and shipbuilder Fincantieri Marine Group to design and build a Jones Act-compliant service operation vessel (SOV) for maintaining offshore wind turbines.
Sudan's Leader Agrees to Host Russian Naval Base on Red Sea
Parliamentary approval is required, and Sudan will need to form a civilian parliament first
Sudan to Finalize Review of Russia’s Red Sea Naval Base Deal
Following the visit of Russian foreign minister Sergey Lavrov in Sudan last week, Moscow and Khartoum have finalized the terms of an agreement on establishing a logistical center for the Russian Navy in Sudan. The news was confirmed during a joint press conference between Lavrov and his Sudanese counterpart Ali al-Sadiq Ali.
Lavrov had earlier met with Sudan’s ruling military leaders Abdel Fattah al-Burhan, the de facto head of state of Sudan, and his deputy Mohamed Hamdan Dagalo. The meeting agenda was reportedly on Russia providing Sudan with weapons in return for a Red Sea Navy base. Lavrov last visited Sudan in 2014 and this was his second visit to Africa this year.
Lavrov vowed to support Sudan’s efforts in lifting the UN arms embargo on the Darfur region. He also pledged further economic cooperation Russia and Sudan. The Kremlin-linked Wagner Group is said to have privileged access to Sudan’s lucrative gold mining industry.
Russia’s naval base deal in Sudan has been in the works since 2019, when the two countries signed an agreement granting the Russian Navy access to Sudanese ports. However, the agreement was made public in 2021, with Sudan’s Chief General of Staff, Gen. Mohammed Othman al-Hussein telling local media that Khartoum would review the agreement.
“This deal was signed under the former National Salvation Government and we are negotiating a possible review, to ensure that our interests and profits are taken into account,” Gen. Othman said at the time.
The deal was derailed after a military coup in October 2021. In addition, Sudan has been without a parliament since 2019 after a popular uprising led to military overthrow of longtime autocrat Omar al Bashir. Parliamentary approval is needed to ratify the naval base agreement, Sudanese military leaders noted.
The deal would allow Russia to set up a naval base with up to 300 Russian troops and up to four navy ships - including nuclear-powered ones - in the strategic Port of Sudan.
The base would ensure a permanent presence of the Russian navy in the Red Sea and the Indian Ocean, and it would spare its ships long voyages to reach the area. The new base would expand on the power-projection support provided by the Russian naval facility in Tartus, Syria.
Yellow evolution: Unique genes led to new species of monkeyflower
Pigment permutations suggest new genes are what make a new species
IMAGE: PLANTS OF THE GENUS MIMULUS (MONKEYFLOWERS) HAVE A GREAT DIVERSITY OF FLOWER COLOR AND SHAPE.view more
CREDIT: YUAN MIMULUS LAB, PETE MORENUS/UCONN
Monkeyflowers glow in a rich assortment of colors, from yellow to pink to deep red-orange. But about 5 million years ago, some of them lost their yellow. In the Feb. 10 issue of Science, UConn botanists explain what happened genetically to jettison the yellow pigment, and the implications for the evolution of species.
Monkeyflowers are famous for growing in harsh, mineral-rich soils where other plants can’t. They are also famously diverse in shape and color. And monkeyflowers provide a textbook example of how a single-gene change can make a new species. In this case, a monkeyflower species lost the yellow pigments in the petals but gained pink about 5 million years ago, attracting bees for pollination. Later, a descendent species accumulated mutations in a gene called YUP that recovered the yellow pigments and led to production of red flowers. The species stopped attracting bees. Instead, hummingbirds pollinated it, isolating the red flowers genetically and creating a new species.
UConn botanist Yaowu Yuan and postdoctoral researcher Mei Liang (currently a professor at South China Agricultural University), with collaborators from four other institutes, have now shown exactly which gene it is that changed to prevent monkeyflowers from making yellow. Their research, published this week in Science, adds weight to a theory that new genes create phenotypic diversity and even new species.
The YUP gene in question is found at a locus, or region, of the monkeyflower genome that has three new genes. These new genes are not found in species outside of this group. They are duplicates of other genes from other parts of the monkeyflower genome. In particular, YUP is a partial duplicate of a pre-existing gene that has nothing to do with color.
Standard genetics thought is that partial duplicate genes regulate the genes they are derived from; it was very unlikely that these genes would affect an unrelated gene. Liang decided to investigate what these genes were doing anyway, against the advice of Yuan, who thought it was a waste of time. But Liang’s persistence paid off: she discovered that the YUP gene was actually targeting the plants’ master regulator of carotenoids, the pigments that make monkeyflowers and other plants yellow. YUP produced many small RNAs that suppressed the carotenoid gene. There are very few examples of genes that produce small RNAs affecting traits important to the creation of a new species.
“This experience really taught me how important it is not to constrain oneself with ‘conventional wisdom’,” Yuan says. Not only does YUP regulate a gene it is entirely unrelated to it; the other two genes at this same locus also affect monkeyflower color, Yuan says.
The uniqueness of these three genes, only found in a few closely related monkeyflowers, is an important clue as to how new species evolve.
“Almost every single species has unique genes,” called ‘taxon specific’ because they are only found in a small group of species. “For the most part, we have no idea what these genes do,” says Yuan. This research shows that these taxon specific genes can be the keys to the new species. Previously, many geneticists and evolutionary biologists thought that it was changes in the expression of common genes shared by many different species that differentiated them, and that the small number of idiosyncratic genes were unlikely to be important.
“We think we understand evolution well enough to make predictions. But now we are realizing we really don’t. Evolution is just so unpredictable,” Yuan says.
His lab is now looking at how the monkeyflower genome controls the production of pigment spatially. For example, some monkeyflowers have upper petals that are entirely white, but lower petals with color. Yuan and his colleagues want to know how the plants suppress pigment only in certain parts of the flower.
Plants of the genus Mimulus (Monkeyflowers) have a great diversity of flower color and shape.
Researchers have calculated the carbon footprint for the full life cycle of fertilisers, which are responsible for approximately five percent of total greenhouse gas emissions – the first time this has been accurately quantified – and found that carbon emissions could be reduced to one-fifth of current levels by 2050.
The researchers, from the University of Cambridge, found that two thirds of emissions from fertilisers take place after they are spread on fields, with one third of emissions coming from production processes.
Although nitrogen-based fertilisers are already known to be a major source of greenhouse gas emissions, this is the first time that their overall contribution, from production to deployment, has been fully quantified. Their analysis found that manure and synthetic fertilisers emit the equivalent of 2.6 gigatonnes of carbon per year – more than global aviation and shipping combined.
Carbon emissions from fertilisers urgently need to be reduced; however, this must be balanced against the need for global food security. Earlier research has estimated that 48% of the global population are fed with crops grown with synthetic fertilisers, and the world’s population is expected to grow by 20% until 2050.
The Cambridge researchers say that a combination of scalable technological and policy solutions are needed to reduce fertiliser emissions while maintaining food security. However, they estimate that if such solutions could be implemented at scale, the emissions from manure and synthetic fertilisers could be reduced by as much as 80%, to one-fifth of current levels, without a loss of productivity. Their results are reported in the journal Nature Food.
Serrenho and his co-author Yunhu Gao undertook a project to accurately measure the total impacts of fertilisers, one of the two main products of the petrochemical industry. Of all the products made by the petrochemical industry, the vast majority – as much as 74% – are either plastics or fertilisers.
“In order to reduce emissions, it’s important for us to identify and prioritise any interventions we can make to make fertilisers less harmful to the environment,” said Serrenho. “But if we’re going to do that, we first need to have a clear picture of the whole lifecycle of these products. It sounds obvious, but we actually know very little about these things.”
The researchers mapped the global flows of manure and synthetic fertilisers and their emissions for 2019, along all stages of the lifecycle, by reconciling the production and consumption of nitrogen fertilisers and regional emission factors across nine world regions.
After completing their analysis, the researchers found that unlike many other products, the majority of emissions for fertilisers occur not during production, but during their use.
“It was surprising that this was the major source of emissions,” said Serrenho. “But only after quantifying all emissions, at every point of the lifecycle, can we then start looking at different mitigation methods to reduce emissions without a loss of productivity.”
The researchers listed and quantified the maximum theoretical impact of different mitigation methods – most of these are already known, but their maximum potential effect had not been quantified.
Emissions from the production of synthetic fertilisers are mostly from ammonia synthesis, partly due to chemical reactions used in the production process. The most effective mitigation at the production stage would be for the industry to decarbonise heating and hydrogen production. Additionally, fertilisers could be mixed with chemicals called nitrification inhibitors, which prevent bacteria from forming nitrous oxide. However, these chemicals are likely to make fertilisers more expensive.
“If we’re going to make fertilisers more expensive, then there needs to be some sort of financial incentive to farmers and to fertiliser companies,” said Serrenho. “Farming is an incredibly tough business as it is, and farmers aren’t currently rewarded for producing lower emissions.”
The single most effective way to reduce fertiliser-associated emissions, however, would be to reduce the amount of fertilisers that we use. “We’re incredibly inefficient in our use of fertilisers,” said Serrenho. “We’re using far more than we need, which is economically inefficient and that’s down to farming practices. If we used fertiliser more efficiently, we would need substantially less fertiliser, which would reduce emissions without affecting crop productivity.”
The researchers also looked at the mix of fertilisers used around the world, which varies by region. The researchers say that replacing some of the fertilisers with the highest emissions, such as urea, with ammonium nitrate worldwide could further reduce emissions by between 20% and 30%. However, this would only be beneficial after decarbonising the fertiliser industry.
“There are no perfect solutions,” said Serrenho. “We need to rethink how we produce food, and what sorts of economic incentives work best. Perhaps that means paying farmers to produce fewer emissions, perhaps that means paying more for food. We need to find the right mix of financial, technological and policy solutions to reduce emissions while keeping the world fed.”
Serrenho and Gao estimate that by implementing all the mitigations they analysed, emissions from the fertiliser sector could be reduced by as much as 80% by 2050.
“Our work gives us a good idea of what’s technically possible, what’s big, and where interventions would be meaningful – it’s important that we aim interventions at what matters the most, in order to make fast and meaningful progress in reducing emissions,” said Serrenho.
The research was part of the C-THRU project, led by Professor Jonathan Cullen, where researchers from four UK and US Universities are working to bring clarity to the emissions from the global petrochemical supply chain.
Nirmatrelvir–ritonavir (Paxlovid) significantly reduced the likelihood of hospitalization or death from COVID-19 in people at risk of severe illness, according to new research in CMAJ (Canadian Medical Association Journal) https://www.cmaj.ca/lookup/doi/10.1503/cmaj.221608.
The study, conducted by Ontario researchers, aimed to evaluate the effectiveness of nirmatrelvir–ritonavir in preventing severe illness during the emergence of the Omicron variant. They looked at data on adults with mild disease who tested positive for SARS-CoV-2 by polymerase chain reaction (PCR) test between April 4 and August 31, 2022, and compared 8876 patients treated with nirmatrelvir–ritonavir with 168 669 who were not treated. Most patients were older than 70 years, were vaccinated and had potential drug–drug interactions.
A previous randomized controlled trial, Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients (EPIC-HR), conducted before the emergence of the Omicron variant had found nirmatrelvir–ritonavir to be effective at treating patients. That trial, however, did not include people who had been vaccinated or who had potential drug–drug interactions.
"Our study, in conjunction with previous clinical trials and observational research, supports the effectiveness of nirmatrelvir–ritonavir at reducing hospital admission from COVID-19 and all-cause death," writes lead author Dr. Kevin Schwartz, Public Health Ontario and ICES, Toronto, Ontario, with coauthors.
They found that for every 62 people treated with nirmatrelvir–ritonavir, the medication prevented 1 case of severe COVID-19.
According to Dr. Schwartz, "This study highlights the importance of testing for SARS-CoV-2 if you have symptoms, and access to Paxlovid for those at risk for severe COVID-19. If you test positive for COVID-19, are over 60 years of age, or if you have other risk factors for severe infection, such as chronic medical conditions or are undervaccinated, contact your health care provider or pharmacy within 5 days of symptoms starting and ask about Paxlovid."
The findings that appear in Lancet Infectious Diseases are from one of the first studies to examine the effectiveness of nirmatrelvir-ritonavir (Paxlovid) in non-hospitalized patients during an Omicron period of the COVID-19 pandemic that includes BA.4 and BA.5 subvariants.
Though many Coloradans are proceeding as though the COVID-19 pandemic is over, the virus continues to circulate, evolve and have an impact—especially for older adults and those with underlying medical conditions. Furthermore, because of the evolution of variants, doctors have fewer treatment options.
“We are really struggling with maintaining effective therapeutic options for high-risk patients with COVID-19,” says Adit Ginde, MD, professor of emergency medicine at the University of Colorado School of Medicine. “Particularly because the monoclonal antibody treatments we had been using and relying on for the past year-and-a-half are no longer effective against recent Omicron subvariants because the virus has changed.”
Right now, the only two effective antiviral treatment options are Paxlovid and Remdesivir. So, Ginde and a team of researchers swung into action to determine if Paxlovid is effective against Omicron variants B.4 and B.5. Ginde is also an emergency medicine physician at the UCHealth University of Colorado Hospital.
“This study was one of the first to strongly suggest a benefit for the antiviral medication, nirmatrelvir-ritonavir, also known as Paxlovid, to prevent hospitalization and death for patients infected with recent Omicron SARS-CoV-2 variants,” said Neil Aggarwal, MD, MHSc, lead author of the study just published in Lancet Infectious Diseases and associate professor of medicine in the University of Colorado School of Medicine. Aggarwal is also a critical care and pulmonary physician at UCHealth University of Colorado Hospital.
The study is what is called “observational”, which means researchers examined the data of patients who had one or more risk factors for severe disease, hospitalization or death—and who either did or did not receive Paxlovid. They evaluated the rate of hospitalization or death and found that the use of Paxlovid significantly reduced rates of hospitalization and death.
Ginde explained that an observational study design using real-world data is meant to imitate a clinical trial. “We used data provided to us from the UCHealth system—a statewide health system and the largest one in Colorado,” Ginde said. This particular study involved 28,000 patients.
Aggarwal explained that Paxlovid was effective in preventing hospitalization among almost all important subgroups of outpatients that were assessed and who qualify for its use under the Emergency Use Authorization (EUA), including those vaccinated. “As a physician who can treat patients in the outpatient setting, I would be very comfortable using Paxlovid as a first-line treatment for adults acutely infected with COVID during the current Omicron phase, vaccinated or not, provided there are no contraindications to its use,” Aggarwal said.
This study is noteworthy as it is one of the first to examine the effectiveness of Paxlovid in non-hospitalized patients during an Omicron period of the COVID-19 pandemic that includes BA.4/BA.5 subvariants. Beyond its effectiveness in keeping patients out of the hospital, Paxlovid was associated with lower rate of post-treatment emergency department visits, that suggests a lower likelihood of more severe rebound symptoms, although the study could not evaluate effect on milder rebound symptoms.
Real world evidence is particularly important for doctors who must make treatment recommendations for their patients. “We provide clinicians with nearly real-time data to help support decision making with robust systematic data,” Ginde said. “If we can confirm benefits of a therapy, clinicians can be confident in prescribing a treatment, and patients can feel comfortable receiving treatment. If we find agents are losing effectiveness, we need to know that as well and change the treatments offered to patients.”
Real world data platforms require multiple collaborations that leverage many components of an academic medical center. Researchers with expertise in informatics, biostatistics, dissemination and implementation, clinical trials and bioethics are all critical.
“It takes a while to build this capability. But once you have the infrastructure, you can use it for COVID and other conditions,” Ginde said. “The FDA has also put out guidance to be able to use real world evidence for regulatory decision-making.”
Ginde and his team plan to publish other real-world study results of the effectiveness of Remdesivir against Omicron subvariants and an update on Paxlovid effectiveness for more recent Omicron subvariants, including XBB.1.5 and BQ.1.
He said, “The laboratory data suggest that Paxlovid is still effective at neutralizing the virus in recent Omicron subvariants. However, we plan to evaluate ongoing clinical effectiveness in patients through our upcoming analyses.”
About the University of Colorado Anschutz Medical Campus
The University of Colorado Anschutz Medical Campus is a world-class medical destination at the forefront of transformative science, medicine, education and patient care. The campus encompasses the University of Colorado health professional schools, more than 60 centers and institutes and two nationally ranked independent hospitals –- UCHealth University of Colorado Hospital and Children's Hospital Colorado -- that treat more than two million adult and pediatric patients each year. Innovative, interconnected and highly collaborative, the University of Colorado Anschutz Medical Campus delivers life-changing treatments, patient care and professional training and conducts world-renowned research fueled by over $690 million in research grants. For more information, visit www.cuanschutz.edu.
JOURNAL
The Lancet
ARTICLE TITLE
Real-world use of nirmatrelvir-ritonavir in COVID-19 outpatients during the era of Omicron variants including BA.4/BA.5: A retrospective cohort study
POST MODERN ALCHEMY
Extracts from two wild plants inhibit COVID-19 virus, study finds
The first major screening of botanical extracts to search for potency against the SARS-CoV-2 virus
IMAGE: EMORY UNIVERSITY GRADUATE STUDENT CAITLIN RISENER, FIRST AUTHOR OF THE STUDY, GATHERS TALL GOLDENROD IN SOUTH GEORGIA.view more
CREDIT: PHOTO BY THARANGA SAMARAKOON
Two common wild plants contain extracts that inhibit the ability of the virus that causes COVID-19 to infect living cells, an Emory University study finds. Scientific Reports published the results — the first major screening of botanical extracts to search for potency against the SARS-CoV-2 virus.
In laboratory dish tests, extracts from the flowers of tall goldenrod (Solidago altissima) and the rhizomes of the eagle fern (Pteridium aquilinum) each blocked SARS-CoV-2 from entering human cells.
The active compounds are only present in miniscule quantities in the plants. It would be ineffective, and potentially dangerous, for people to attempt to treat themselves with them, the researchers stress. In fact, the eagle fern is known to be toxic, they warn.
“It’s very early in the process, but we’re working to identify, isolate and scale up the molecules from the extracts that showed activity against the virus,” says Cassandra Quave, senior author of the study and associate professor in Emory School of Medicine’s Department of Dermatology and the Center for the Study of Human Health. “Once we have isolated the active ingredients, we plan to further test for their safety and for their long-range potential as medicines against COVID-19.”
Quave is an ethnobotanist, studying how traditional people have used plants for medicine to identify promising new candidates for modern-day drugs. Her lab curates the Quave Natural Product Library, which contains thousands of botanical and fungal natural products extracted from plants collected at sites around the world.
Caitlin Risener, a PhD candidate in Emory’s Molecular and Systems Pharmacology graduate program and the Center for the Study of Human Health, is first author of the current paper.
In previous research to identify potential molecules for the treatment of drug-resistant bacterial infections, the Quave lab focused on plants that traditional people had used to treat skin inflammation.
Given that COVID-19 is a newly emerged disease, the researchers took a broader approach. They devised a method to rapidly test more than 1,800 extracts and 18 compounds from the Quave Natural Product Library for activity against SARS-CoV-2.
“We’ve shown that our natural products library is a powerful tool to help search for potential therapeutics for an emerging disease,” Risener says. “Other researchers can adapt our screening method to search for other novel compounds within plants and fungi that may lead to new drugs to treat a range of pathogens.”
SARS-CoV-2 is an RNA virus with a spike protein that can bind to a protein called ACE2 on host cells. “The viral spike protein uses the ACE2 protein almost like a key going into a lock, enabling the virus to break into a cell and infect it,” Quave explains.
The researchers devised experiments with virus-like particles, or VLPs, of SARS-CoV-2, and cells programmed to overexpress ACE2 on their surface. The VLPs were stripped of the genetic information needed to cause a COVID-19 infection. Instead, if a VLP managed to bind to an ACE2 protein and enter a cell, it was programmed to hijack the cell’s machinery to activate a fluorescent green protein.
A plant extract was added to the cells in a petri dish before introducing the viral particles. By shining a fluorescent light on the dish, they could quickly determine whether the viral particles had managed to enter the cells and activate the green protein.
The researchers identified a handful of hits for extracts that protected against viral entry and then homed in on the ones showing the strongest activity: Tall goldenrod and eagle fern. Both plant species are native to North America and are known for traditional medicinal uses by Native Americans.
Additional experiments showed that the protective power of the plant extracts worked across four variants of SARS-CoV-2: Alpha, theta, delta and gamma.
To further test these results, the Quave lab collaborated with co-author Raymond Schinazi, Emory professor of pediatrics, director of Emory’s Division of Laboratory of Biochemical Pharmacology and co-director of the HIV Cure Scientific Working Group within the NIH-sponsored Emory University Center for AIDS Research. A world leader in antiviral development, Schinazi is best known for his pioneering work on breakthrough HIV drugs.
The higher biosecurity rating of the Schinazi lab enabled the researchers to test the two plant extracts in experiments using infectious SARS-CoV-2 virus instead of VLPs. The results confirmed the ability of the tall goldenrod and eagle fern extracts to inhibit the ability of SARS-CoV-2 to bind to a living cell and infect it.
“Our results set the stage for the future use of natural product libraries to find new tools or therapies against infectious diseases," Quave says.
As a next step, the researchers are working to determine the exact mechanism that enables the two plant extracts to block binding to ACE2 proteins.
For Risener, one of the best parts about the project is that she collected samples of tall goldenrod and eagle fern herself. In addition to gathering medicinal plants from around the globe, the Quave lab also makes field trips to the forests of the Joseph W. Jones Research Center in South Georgia. The Woodruff Foundation established the center to help conserve one of the last remnants of the unique longleaf pine ecosystem that once dominated the southeastern United States.
“It’s awesome to go into nature to identify and dig up plants,” Risener says. “That’s something that few graduate students in pharmacology get to do. I’ll be covered in dirt from head to toe, kneeling on the ground and beaming with excitement and happiness.”
She also assists in preparing the plant extracts and mounting the specimens for the Emory Herbarium.
“When you collect a specimen yourself, and dry and preserve the samples, you get a personal connection,” she says. “It’s different from someone just handing you a vial of plant material in a lab and saying, ‘Analyze this.’”
After graduating, Risener hopes for a career in outreach and education for science policy surrounding research into natural compounds. A few of the more famous medicines derived from botanicals include aspirin (from the willow tree), penicillin (from fungi) and the cancer therapy Taxol (from the yew tree).
“Plants have such chemical complexity that humans probably couldn’t dream up all the botanical compounds that are waiting to be discovered,” Risener says. “The vast medicinal potential of plants highlights the importance of preserving ecosystems.”
Co-authors of the current paper include: Sumin Woo, Tharanga Samarakoon, Marco Caputo and Emily Edwards (the Quave lab and Emory’s Center for the Study of Human Health); Keivan Zandi, Shu Ling Goh and Jessica Downs-Bowen (the Schinazi lab); Kier Klepzig (Joseph W. Jones Research Center); and Wendy Applequist (Missouri Botanical Garden).
Funding for the paper was provided by the Marcus Foundation, the NIH-funded Center for AIDS Research and the NIH National Center for Complementary and Integrative Health.
