By Elise Ma

One day after the U.S. began the first human trial of an mRNA vaccine candidate for COVID-19 on March 16, China said Tuesday evening that it had approved the first clinical trial of a vaccine candidate developed by domestic researchers.

The vaccine candidate, known as Ad5-nCoV, is a recombinant novel coronavirus vaccine. It was jointly developed by Tianjin-based Cansino Biologics Inc. and the Institute of Biotechnology of the Academy of Military Medical Sciences. The clinical trial will enroll 108 subjects and take place at Tongji Hospital in Wuhan, the epicenter of COVID-19.

Cansino said Ad5-nCoV is a genetically engineered vaccine candidate with the replication-defective adenovirus type 5 as the vector to express SARS-CoV-2 spike protein. The vaccine candidate is intended to be used to prevent the disease caused by the novel coronavirus infection.

Backed by the state, the company has also obtained support from the Tianjin Science and Technology Bureau through the Project on Emergency Prevention and Control of COVID-19 Infection to develop the vaccine.

On March 17, the company said it has started to prepare for clinical trials of Ad5-nCoV and the pre-screening of healthy volunteers.

Cansino CEO Xuefeng Yu said the company and the academy have been collaborating closely since late January to develop Ad5-nCoV and generate sound scientific data to support its IND filing. “Having committed to providing unconditional support to fight against the global epidemic, Cansino is determined to launch our vaccine product candidate as soon as possible, with no compromises in quality and safety,” he added.

According to the Chinese Clinical Trial Registry, it is a single-center, open and dose-escalation phase I trial testing safety and tolerance of Ad5-nCoV in healthy adults, ages 18 to 60. The low-, middle- and high-dosage groups will each see 36 patients, who will receive 5e10vp, 1E11vp and 1E11vp of Ad5-nCoV, respectively.

The primary indicator is to see whether there are adverse reactions seven days after injection, and the secondary indicators are whether adverse reactions are observed 28 days after injection or severe adverse reactions six months after the injection.

Researchers will also look for anti-S antibody immunoglobulin G, neutralizing antibodies against SARS-CoV-2, neutralizing antibodies against Ad5 and specific T-cell responses as secondary indicators.

Ad5-nCoV is developed with Cansino’s adenovirus-based viral vector vaccine technology platform, which utilizes adenoviruses as viral vectors to deliver vaccine antigens to the human cell. Previously, the technology platform was key in enabling Cansino to translate its Ebola virus disease vaccine, Ad5-EBOV, from a concept to an approved product in merely three years.

A forerunner in China’s vaccine space, Cansino came to the industry’s attention when its Ad5-EBOV became the first approved Ebola virus vaccine in China for emergency use and as part of the national stockpile in October 2017.

Leveraging the existing technology platform, Cansino said results from preclinical animal studies of Ad5-nCoV show that the vaccine candidate can induce strong immune responses in animal models. The preclinical animal safety studies demonstrated a good safety profile.

“We have completed the necessary preclinical steps for vaccine R&D. To date, the GMP clinical batches have passed quality testing and are ready for the phase I clinical trial,” the company said.

Stepping carefully

A cautious scientist, Yu stressed the importance of safety in vaccine development and warned that there is more to think of than just the speed of development.

“We need speed, but we still need quality. We d

on’t want to introduce a second harm to people. It is critically important to check every step,” Yu said in a webinar organized by Chinese CRO Wuxi Apptec last month.

He said although the existing technology platform can speed up the development of a vaccine, there are issues to address before applying any vaccine to a human. Animal models should be available before moving any vaccine candidates into human trials so as to produce a vaccine that will eventually work without concerns such as disease enhancement.

“Even though we have learned from MERS and SARS, COVID-19 is still a new virus that behaves very differently, so we should really get some basic understanding,” Yu said.

And in developing a vaccine for emergency response, Yu said it would be ideal to require just one dose, and developers need to consider the manufacturability of the vaccine in order to benefit more people.

On March 16, the NIH said a phase I trial has begun in Seattle. The vaccine candidate, known as mRNA-1273 and co-developed by NIH and Moderna Inc., encodes viral spike (S) protein for prevention of COVID-19.

By Anette Breindl

The first attempt at using existing drugs to treat patients infected with SARS-CoV-2 has yielded disappointing results.

In 200 hospitalized patients with severe COVID-19, a 14-day regimen of twice-daily treatment with Kaletra/Aluvia (lopinavir/ritonavir, Abbvie Inc.) did not hasten recovery when added to the standard of care. Chinese clinicians led by Bin Cao of the National Clinical Research Center for Respiratory Diseases reported their findings in the March 19, 2020, issue of The New England Journal of Medicine.

Lopinavir is a protease inhibitor, while ritonavir increases the half-life of lopinavir by inhibiting its metabolism. The drug was tested because screening studies had flagged it as having activity against MERS-CoV, which has led to a clinical trial of a combination of Kaletra/Aluvia and interferon-beta for the treatment of MERS-CoV in the Kingdom of Saudi Arabia.

In the COVID-19 trial, 199 patients were treated, split evenly between drug and standard-of-care groups. The study’s primary endpoint, time to improvement, was the same between the two groups, both of which took 16 days to improve. Mortality and viral load at various time points were also not different.

In an editorial published alongside the paper, Lindsey Baden, of Harvard Medical School, and Eric Rubin, of the Harvard TH Chan School of Public Health, wrote that “the results for certain secondary endpoints are intriguing,” but also acknowledged that those results were hard to interpret, due to a mix of trial size, possible differences in illness severity at baseline, and the fact that the trial was randomized but not blinded.

And if certain endpoints were intriguing, others were discouraging. In particular, viral loads did not differ between the groups, tellingly so, according to Baden and Rubin. “Since the drug is supposed to act as a direct inhibitor of viral replication, the inability to suppress the viral load and the persistent detection of viral nucleic acid strongly suggest that it did not have the activity desired,” they wrote. “Thus, although some effect of the drug is possible, it was not easily observed.”

It is possible that larger trials will yet uncover an effect of Kaletra/Aluvia. But for now, perhaps the best hope is that other drugs will work better – in particular, remdesivir (Gilead Sciences Inc.), which was originally developed for Ebola virus disease, but proved less effective there than several other options.

A paper in the Jan. 10, 2020, issue of Nature Communications investigated the effects of Aluvia on MERS-CoV in mouse experiments, where it showed ho-hum effects. The authors of the Nature Communications paper reported that “prophylactic [Kaletra/Aluvia plus interferon-beta] slightly reduces viral loads without impacting other disease parameters.”

But remdesivir was more effective. “Both prophylactic and therapeutic [remdesivir] improve pulmonary function and reduce lung viral loads and severe lung pathology” in a mouse model of MERS, the authors reported.

Remdesivir is in both an NIH-sponsored clinical trial and a Japanese-Chinese trial as potential COVID-19 treatment, after a January case report of a patient who showed rapid improvement after he was treated with the drug for COVID-19.

Though the Kaletra/Aluvia trial’s results were not as hoped, Baden and Rubin noted that the trial itself was an encouraging bit of news, as well as a “heroic effort…. As we saw during the 2014 Ebola outbreak in West Africa, obtaining high-quality clinical trial data to guide the care of patients is extremely difficult in the face of an epidemic, and the feasibility of a randomized design has been called into question. Yet Cao’s group of determined investigators not only succeeded but ended up enrolling a larger number of patients (199) than originally targeted.”

Coronavirus could live up to three days on a plastic or stainless steel doorknob, researchers found.

A preliminary study released last week also showed that the virus could be aerosolized, meaning it could potentially live in the air. It could live up to three days on some surfaces.

Though it’s widely acknowledged that coronavirus could be spread via respiratory droplet — the result of coughing or sneezing — there’s not much information yet on how the virus lives on surfaces or in the air.

The new research could inform cleaning recommendations and other measures taken to reduce community spread.

The U.S. Centers for Disease Control and Prevention recommend routine cleaning of high-touch surfaces, like door handles, high-backed chairs, light switches and remote controls.

The study, released last week, is not yet peer-reviewed. That means that other experts have not had the chance to check the quality of the research, and its not advised that doctors use it in a clinical setting. But as people try to cope with the disease, it’s being widely read.

Here’s how long the study indicated the virus could live on various surfaces:

The air: Researchers found the virus could be detected in aerosols up to 4 hours after it was sprayed.

Copper: Up to 4 hours

Cardboard: Up to 24 hours

Plastic: 2-3 days

Stainless steel: 2-3 days

Researchers have discovered a unique petroglyph, depicting what appears to be a six-legged mantis-man, at the Teymareh rock art site in Iran.

Invertebrates are rarely found in rock carvings, so the archaeologists on the project recruited entomologists to help them determine what kinds of creatures might have inspired the motif. Researchers looked at several six-legged species that prehistoric artists might have come across in central Iran.

The motif measures just 5.5 inches in length, and though it was discovered in 2017, its small size and unusual shape made it difficult to identify. In addition to boasting six legs, the creature features large eyes and enlarged pincher-like forearms.

The entomologists on the study identified an extension on the creature’s head that matches local praying mantis species belonging to the genus Empusa.

Scientists estimate the rock art is between 4,000 and 40,000 years old.

“The petroglyph proves that praying mantids have been astounding and inspiring humans since prehistoric times,” researchers wrote in the Journal of Orthoptera.

The figure isn’t a perfect representation of a Empusa mantis, as the middle limbs feature loops as a hands. Researchers linked the carving with a common petroglyph motif known as “Squatter Man,” which has been found at rock art sites around the world. The motif features a person flanked by circles.

Some researchers suggest the circles represent the atmospheric plasma discharges created by auroras.

The discovery of the latest petroglyph reinforces the theory, based on previous discoveries of half-mantid, half-human figures, that the mantis was a symbol for the supernatural.

“An example includes several prehistoric pictographs in southern Africa representing ‘mantis people’ with half-mantid bodies,” researchers wrote in their paper. “These, and the Iranian mantid petroglyph, bear witness that in prehistory, almost as today, praying mantids were animals of mysticism and appreciation.”

A woman falsely claimed she had coronavirus at a security checkpoint at Cleveland Hopkins International Airport, shutting down the checkpoint for 20 minutes, officials said.

By Adam Ferrise

A Los Angeles woman caused the temporary closure of a security checkpoint at Cleveland Hopkins Airport Sunday after she told a TSA agent that she contracted the coronavirus.

The woman licked her fingers as she handed her driver’s license to the agent, Cleveland police and the TSA said.

The 63-year-old woman was not arrested and criminal charges were not filed as of Monday afternoon. Police reports say the woman could face a charge of inducing panic.

The incident caused the checkpoint to close for 20 minutes for the area to be cleaned, according to police and a TSA spokeswoman. The TSA spokeswoman said the agency plans to pursue a civil citation against the woman, which could result in a fine.

The incident happened as coronavirus continues to spread in Ohio and Cuyahoga County. Of the 50 confirmed coronavirus cases in Ohio so far, 24 are in Cuyahoga County.

Airport spokeswoman Michele Dynia referred questions about airport operations to Cleveland’s Joint Information Center. A woman answering the phone there said she could not immediately answer any questions about the woman’s encounter with the agent.

The incident happened about 5:20 p.m. Sunday. The woman walked up to the TSA checkpoint, licked her fingers just before handing her driver’s license to a TSA agent, and said: “Good thing you are wearing gloves because I just licked my fingers and I have coronavirus,” according to police reports.

TSA agents called for the Cleveland fire and medics posted at the airport to respond. The woman denied telling the TSA agent she had coronavirus, but said she did lick her fingers and told the agent she was glad he was wearing gloves, police reports say. She told officers she had no health issues and did not have coronavirus.

An airline banned her from flying on Sunday, according to the TSA. TSA agents prohibited the woman from entering the airport for 24 hours, according to the police report.

A fold (shape) that may have been one of the earliest proteins in the evolution of metabolism. Credit: Vikas Nanda/Rutgers University

Rutgers researchers have discovered the origins of the protein structures responsible for metabolism: simple molecules that powered early life on Earth and serve as chemical signals that NASA could use to search for life on other planets.

Their study, which predicts what the earliest proteins looked like 3.5 billion to 2.5 billion years ago, is published in the journal Proceedings of the National Academy of Sciences.

The scientists retraced, like a many thousand piece puzzle, the evolution of enzymes (proteins) from the present to the deep past. The solution to the puzzle required two missing pieces, and life on Earth could not exist without them. By constructing a network connected by their roles in metabolism, this team discovered the missing pieces.

“We know very little about how life started on our planet. This work allowed us to glimpse deep in time and propose the earliest metabolic proteins,” said co-author Vikas Nanda, a professor of Biochemistry and Molecular Biology at Rutgers Robert Wood Johnson Medical School and a resident faculty member at the Center for Advanced Biotechnology and Medicine. “Our predictions will be tested in the laboratory to better understand the origins of life on Earth and to inform how life may originate elsewhere. We are building models of proteins in the lab and testing whether they can trigger reactions critical for early metabolism.”

A Rutgers-led team of scientists called ENIGMA (Evolution of Nanomachines in Geospheres and Microbial Ancestors) is conducting the research with a NASA grant and via membership in the NASA Astrobiology Program. The ENIGMA project seeks to reveal the role of the simplest proteins that catalyzed the earliest stages of life.

“We think life was built from very small building blocks and emerged like a Lego set to make cells and more complex organisms like us,” said senior author Paul G. Falkowski, ENIGMA principal investigator and a distinguished professor at Rutgers University-New Brunswick who leads the Environmental Biophysics and Molecular Ecology Laboratory. “We think we have found the building blocks of life—the Lego set that led, ultimately, to the evolution of cells, animals and plants.”

The Rutgers team focused on two protein “folds” that are likely the first structures in early metabolism. They are a ferredoxin fold that binds iron-sulfur compounds, and a “Rossmann” fold, which binds nucleotides (the building blocks of DNA and RNA). These are two pieces of the puzzle that must fit in the evolution of life.

Proteins are chains of amino acids and a chain’s 3-D path in space is called a fold. Ferredoxins are metals found in modern proteins and shuttle electrons around cells to promote metabolism. Electrons flow through solids, liquids and gases and power living systems, and the same electrical force must be present in any other planetary system with a chance to support life.

There is evidence the two folds may have shared a common ancestor and, if true, the ancestor may have been the first metabolic enzyme of life.

A new AI can detect odours in a two-step process that mimics the way our noses smell

An AI can sniff out certain scents, giving us a glimpse of how our nose might work in detecting them.

Thomas Cleland at Cornell University, New York, and Nabil Imam at tech firm Intel created an AI based on the mammalian olfactory bulb (MOB), the area of the brain that is responsible for processing odours. The algorithm mimics a part of the MOB that distinguishes between different smells that are usually present as a mixture of compounds in the air.

This area of the MOB contains two key types of neuron: mitral cells, which are activated when an odour is present but don’t identify it, and granule cells that learn to become specialised and pick out chemicals in the smell. The algorithm mimics these processes, says Imam.

Cleland and Imam trained the AI to detect 10 different odours, including those of ammonia and carbon monoxide. They used data from previous work that recorded the activity of chemical sensors in a wind tunnel in response to these smells.

When fed that data, the AI learns to detect that a smell is present based on the sensors’ responses to the chemicals, and then goes on to identify it on the basis of the patterns in that data. As it does so, the AI has a spike of activity analogous to the spikes of electrical activity in the human brain, says Imam.

The AI refined its learning over five cycles of exposure, eventually showing activity spikes specific to each odour. The researchers then tested the AI’s ability to sniff out smells among others that it hadn’t been trained to detect. They considered an odour successfully identified when the AI’s fifth spike pattern matched or was similar to the pattern produced by the sensors.

The AI got it almost 100 per cent correct for eight of the smells and about 90 per cent correct for the remaining two. To test how it might identify odorous contaminants in the environment, the researchers blocked 80 per cent of the smell signal to mimic more realistic scenarios. In these tests, the AI’s accuracy dipped to less than 30 per cent.

“I think the link [to the MOB] is quite strong – this algorithm might be an explanation to how it works in the human nose, to some abstraction,” says Thomas Nowotny at the University of Sussex, UK. But the AI’s ability to solve real life problems, such as detecting bombs by picking out hazardous smells associated with them, is still some way off, he says.

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