Toward One Drug to Treat All Coronaviruses

Safe and effective vaccines offer hope for an end to the COVID-19 pandemic. However, the possible emergence of vaccine-resistant SARS-CoV-2 variants, as well as novel coronaviruses, make finding treatments that work against all coronaviruses as important as ever. Now, researchers reporting in ACS’ Journal of Proteome Research have analyzed viral proteins across 27 coronavirus species and thousands of samples from COVID-19 patients, identifying highly conserved sequences that could make the best drug targets.

Drugs often bind inside “pockets” on proteins that hold the drug snugly, causing it to interfere with the protein’s function. Scientists can identify potential drug-binding pockets from the 3D structures of viral proteins. Over time, however, viruses can mutate their protein pockets so that drugs no longer fit. But some drug-binding pockets are so essential to the protein’s function that they can’t be mutated, and these sequences are generally conserved over time in the same and related viruses. Matthieu Schapira and colleagues wanted to find the most highly conserved drug-binding pockets in viral proteins from COVID-19 patient samples and from other coronaviruses, revealing the most promising targets for pan-coronavirus drugs.

The team used a computer algorithm to identify drug-binding pockets in the 3D structures of 15 SARS-CoV-2 proteins. The researchers then found corresponding proteins in 27 coronavirus species and compared their sequences in the drug-binding pockets. The two most conserved druggable sites were a pocket overlapping the RNA binding site of the helicase nsp13, and a binding pocket containing the catalytic site of the RNA-dependent RNA polymerase nsp12. Both of these proteins are involved in viral RNA replication and transcription. The drug-binding pocket on nsp13 was also the most highly conserved across thousands of SARS-CoV-2 samples taken from COVID-19 patients, with not a single mutation. The researchers say that novel antiviral drugs targeting the catalytic site of nsp12 are currently in phase II and III clinical trials for COVID-19, and that the RNA binding site of nsp13 is a previously underexplored target that should be a high priority for drug development.

Source: American Chemical Society

Researchers Discover Certain Materials Combined with UV light Can Kill Coronavirus

Kim Delker and Rachel Whitt wrote . . . . . . . . .

As the deadly COVID-19 pandemic continues to wreak havoc around the world with no end in sight, new ways in which to stop the spread or mitigate the effects of the disease are few.

Although most experts agree that a vaccine would significantly slow or eventually stop the spread, the work to develop, approve and distribute such a vaccine are likely months away. That leaves us with only prevention efforts such as masks, social distancing and disinfecting, which partially due to human inconsistencies in behavior, have proven to be variable in effectiveness.

Despite these grim realities about the novel coronavirus that has taken 2020 by storm, disrupting the work, school and personal lives of nearly everyone on the globe, some University of New Mexico researchers have found a possible breakthrough in how to manage this virus, as well as future ones.

A team led by the Center for Biomedical Engineering faculty David Whitten, Distinguished Professor in the Department of Chemical and Biological Engineering, along with Eva Chi and Linnea Ista, faculty members in the same department, have found some light at the end of the tunnel, so to speak.

The main finding of their research, highlighted in the paper, “Highly Effective Inactivation of SARS-CoV-2 by Conjugated Polymers and Oligomers,” published this week in the journal ACS Applied Materials & Interfaces, involves the ability of the combination of certain polymers and oligomers, when combined with UV light, to almost completely kill the coronavirus.

Although disinfectants such as bleach or alcohol are effective against the virus, they are volatile and corrosive, which limit lasting sterilization of surfaces treated by these products, Whitten said.

What is different about these polymer and oligomer materials is that when activated with UV light, they provide a coating that is shown to be fast acting and highly effective, reducing the concentration of the virus by five orders of magnitude, Chi said.

“These materials have shown to have broad-spectrum antiviral properties,” she said.

Whitten points out that in order for the material to be active against the virus, it must be exposed to light. Light activates the “docking” process that is important and necessary for placing the oligomer or polymer at the surface of the virus particle, allowing the absorption of light that generates the reactive oxygen intermediate at the surface of the virus particle.

“As far as we know so far, materials such as ours are not active against SARS-CoV-2 in the dark and require activation by irradiation with ultraviolet or visible light, depending on where the specific antimicrobial absorbs light,” he said. “In the dark, our antimicrobial materials ‘dock’ with the virus, and then on irradiation, they activate oxygen. It is this active, excited state of oxygen that starts the chain of reactions that inactivate the virus.”

And this science can easily be applied into consumer, commercial and healthcare products, such as wipes, sprays, clothing, paint, personal protective equipment (PPE) for healthcare workers, and really almost any surface.

“When incorporated into N95 masks, this material works well against the virus,” Chi said. “In addition to trapping the virus in a mask, this would make for better PPE and prolong its life.”

Another unique advantage of this material is that unlike traditional disinfectant products, it is shown to not wash away with water and leaves no toxic residue as a result of the photodegradation process, Chi said.

Studying the potential of conjugated polymers and oligomers is nothing new for UNM researchers. In fact, Whitten and another of the authors on the study, Kirk Schanze, have been researching this area for a couple of decades.

Whitten and Chi said colleagues such as Schanze and others have collected a lot of data on polymer and oligomers, so when the pandemic hit in the spring, Whitten almost immediately started wondering how his area of study could help.

“It was the right timing for all of us,” Chi said.

Acquiring live coronavirus for research is not an easy feat, but thanks to the efforts a couple of team members, they were able to make it happen.

Linnea Ista is a member of the Biosafety Committee at UNM, and when the pandemic broke out and she was aware of the research that Whitten and Chi were conducting, she realized that she may have a connection on how to make the research happen, due to the fact that representatives from UNM’s School of Medicine also sit on the committee.

Alison Kell, a faculty member in the School of Medicine, was the one who was able to acquire the live coronavirus for testing the effectiveness of these materials. She has been working with the SARS-CoV-2 virus in her research and was able to develop a protocol for analyzing samples the team prepared and exposing them to near UV or visible light.

Due to the sensitive nature of working with a virus such as coronavirus, it was crucial for Kell to be part of the team, since the work had to be done in cooperation with the UNM School of Medicine, which has BSL-3 lab facilities that are essential to doing study on the highly-contagious active virus, Ista said.

Whitten said he is hopeful that this discovery can quickly be put into use. He has a company called BioSafe Defenses that he said has hired a former Environmental Protection Agency official to help expedite the regulatory process in taking this discovery to market. He anticipates that once a material is approved, it will be only a matter of months before wipes, masks and other products are in the marketplace.

He said their research has found that adding the material into wipes would add only pennies per wipe. Additionally, the material could be added into masks and other personal protective equipment, changing the game for businesses such as gyms, airlines, cruise ships, groceries, health care facilities, schools and many more industries. In addition to coronavirus, these products could also help eliminate infections by the common cold, seasonal flu and other viral and bacterial infections that plague millions of people annually, causing loss of work and school time.

“There is a limitless market for this,” he said.

He added that the current pandemic is likely not the last such public health crisis we will see, so even after a vaccine for coronavirus is available, such products could be useful in combatting a wide variety of viruses and bacteria, including the flu or common cold.

“We’re not just thinking about COVID but other pathogens and any viral agents,” Whitten said. “We want to be ready for the next pandemic.”

Source: The University of New Mexico

Coronavirus in a Cough: Tests Show Masks Stopping the Spread

A cough could spread a cloud of COVID-19 throughout a room, but a face mask can greatly shrink the size and spread of that cloud, a new study finds.

In fact, the volume of the cloud without a mask is about seven times larger than with a surgical mask and 23 times larger than with an N95 mask, the researchers found.

“We found that anything that reduces the distance traveled by the cloud, such as a mask, handkerchief, or coughing into an elbow, should greatly reduce the region over which the droplets disperse upon coughing, and therefore the chances of infection,” said researcher Rajneesh Bhardwaj, from the Indian Institute of Technology Bombay, in Mumbai.

Using jet theory and data from the literature, Bhardwaj and colleague Amit Agrawal found the first 5 to 8 seconds after coughing is critical for suspending droplets in the air and the spread of the disease. After that, the cough cloud starts to break up.

The study findings helped the researchers develop a formula to determine the maximum number of people that can be in a hospital ward, and the rate at which air in a room, elevator, movie theater, car, plane cabin or restaurant needs to be circulated to keep the air fresh and reduce the odds of infection.

The report was published online in the journal Physics of Fluids.

“We estimate this volume of the air, which may help to design ventilation of closed spaces and consequently reduce the spread of the disease,” Agrawal said in a news release from the American Institute of Physics.

Source: HealthDay

China’s CDC: Frozen Food Package Polluted by Living Coronavirus Could Cause Infection

Roxanne Liu and Tony Munroe wrote . . . . . . . . .

China’s disease control authority said on Saturday that contact with frozen food packaging contaminated by living new coronavirus could cause infection.

The conclusion came as the Chinese Center for Disease Control and Prevention (CDC) detected and isolated living coronavirus on the outer packaging of frozen cod during efforts to trace the virus in an outbreak reported last week in the city of Qingdao, the agency said on its website.

The finding, a world first, suggests it is possible for the virus to be conveyed over long distances via frozen goods, it said.

Two dock workers in Qingdao who were initially diagnosed as asymptomatic infections in September brought the virus to a chest hospital during quarantine due to insufficient disinfection and protection, leading to another 12 infections linked to the hospital, authorities said last week.

However, the CDC’s latest statement does not show solid proof that the two workers in Qingdao caught the virus from the packaging directly, rather than contracting the virus from somewhere else and then contaminating the food packaging they handled, said Jin Dong-Yan, a virology professor at the University of Hong Kong.

The CDC said no instance had been found of any consumer contracting the virus by having contact with frozen food and the risk of this happening remained very low.

Nonetheless it advised that workers who handle, process and sell frozen products should avoid direct skin contact with products that could possibly be polluted.

Staff should not touch their mouth or nose before taking off work garments that could possibly be contaminated without washing their hands and should take tests regularly, the agency said.

Prior to the CDC’s latest findings genetic traces of the virus had been found in some samples taken from frozen food or food packaging, but the amount of virus was low and no living virus was isolated, the agency said.

Only living virus can infect people, while samples containing dead virus could also test positive for virus traces, Jin said.

Source: Reuters

Coronavirus Can Infect Your Eyes as Well as Your Lungs

Amy Norton wrote . . . . . . . . .

COVID-19 is primarily a respiratory infection, but experts have suspected the virus can also infiltrate the eyes. Now, scientists have more direct evidence of it.

The findings are based on a patient in China who developed an acute glaucoma attack soon after recovering from COVID-19. Her doctors had to perform surgery to treat the condition, and tests of her eye tissue showed evidence of SARS-CoV-2.

The case offers proof that “SARS-CoV-2 can also infect ocular tissues in addition to the respiratory system,” the doctors reported in the Oct. 8 online edition of the journal JAMA Ophthalmology.

“It’s been suspected that the eyes can be a source of both ‘in’ and ‘out'” for the novel coronavirus, said Dr. Aaron Glatt, a spokesman for the Infectious Diseases Society of America.

That’s why health care workers protect their eyes with goggles or face shields, he noted.

It’s not possible to say whether the patient in this case contracted SARS-CoV-2 via her eyes, according to Glatt. But that is a possibility — whether through viral particles in the air or by touching her eyes with a virus-contaminated hand, he said.

Another big unknown is whether any lingering virus in patients’ eye tissue will cause problems.

According to Dr. Grace Richter, an ophthalmologist at the University of Southern California’s Roski Eye Institute in Los Angeles, “It’s too early to know what having this virus floating around in the eye means for ocular health.”

At this point, Richter said, limited eye problems have been seen with COVID-19: A small number of patients develop conjunctivitis (“pink eye”), where the white part of the eye and inside of the eyelid become swollen, red and itchy.

The patient in this case suffered acute angle-closure glaucoma — a serious condition in which pressure in the eyes suddenly rises due to fluid buildup. It requires prompt treatment to relieve the pressure, sometimes with surgery to restore the eye’s normal fluid movement.

Richter was doubtful the coronavirus directly caused the eye complication. In general, certain anatomical features of the eye make some people vulnerable to acute angle-closure glaucoma, and it can be triggered by medications, she explained.

Richter speculated that since the patient was hospitalized and likely received various drugs, that might have been the cause.

That is possible, agreed Dr. Sonal Tuli, a clinical spokeswoman for the American Academy of Ophthalmology and chairwoman of ophthalmology at the University of Florida College of Medicine, in Gainesville.

Tuli said the patient’s case is “interesting,” but leaves open a number of questions. One is whether the virus present in the eye tissue is actually infectious.

The patient was a 64-year-old woman who was hospitalized for COVID-19 on Jan. 31. Eighteen days later, her symptoms had fully resolved, and throat swabs turned up negative for SARS-CoV-2.

About a week later, though, she developed pain and vision loss in one eye, and then in her other eye a few days afterward, according to the report by Dr. Ying Yan and colleagues at the General Hospital of the Central Theater Command in Wuhan, China.

The patient landed in the hospital again, where she was diagnosed with acute angle-closure glaucoma and cataract. Medication failed to bring down her eye pressure, so her doctors performed surgery — taking tissue samples in the process.

Tests of those samples turned up evidence that SARS-CoV-2 had invaded the eye tissues, Yan’s team reported.

While it’s not clear how the virus got into the patient’s eyes, the experts agreed the case underscores the importance of eye protection. For health care providers, that means goggles and face shields; for the average person, it’s regular hand-washing and keeping the hands away from the eyes.

“I think people don’t realize how often they touch their eyes,” Tuli said.

That advice will reduce the chance of any virus, including cold and flu bugs, from coming into contact with the eyes, she noted.

While that may be enough in most cases, people caring for someone with COVID-19 at home may want to be extra cautious, Tuli suggested. Wearing eye protection in addition to a mask is a “good idea,” she said.

Source: HealthDay