Posts tagged with "SARS-Cov-2"

Kaelen Felix Illustrates a Dental Article for 360 MAGAZINE

Oral Hygiene × SARS-CoV-2

The British Dental Journal recently found that poor oral hygiene may be linked to more severe cases of COVID-19 because of the harmful bacteria found in mouths that have not been properly taken care of.

While the mouth has always been known as a gateway to the rest of the body, giving it the ability to cause problems in other areas, it is now found that poor oral hygiene can cause respiratory infections, making COVID-19 stronger.

The good news is that the best defense, in this scenario, is to follow good oral practices, like flossing, brushing and using mouthwash.

COVID-19 continues to be deadly, but there does appear to be some sort of link in more than half of fatal cases.

According to the British Dental Journal, “More than 80% of COVID-19 patients in ICUs exhibited an exceptionally high bacterial load, with more than 50% of deaths exhibiting bacterial superinfections.”

Even though COVID-19 is transferred virally, complications like pneumonia and acute respiratory distress might be caused by bacterial superinfection, which begins in the mouth.

The study says, “We recommend that oral hygiene be maintained, if not improved, during a SARS-CoV-2 infection in order to reduce the bacterial load in the mouth and the potential risk of a bacterial superinfection.”

Again, hygiene can be maintained by brushing, flossing and using mouthwash, but oral-care probiotics can also offer protection.

Oral-care probiotics are a specialized type of probiotic formulated to repopulate the oral cavity bacteria, which battles harmful bacteria that could lead to cavities, gingivitis and periodontal disease.

Dr. Eric Goulder, founder of the Heart and Stroke Prevention Center of Central Ohio, said he thinks heart health is also determined by oral health. His team uses ProBiora, which supports health in teeth and gums.

“We think everyone should be extra careful during the pandemic, and oral-care probiotics are a great way to help keep the oral cavity in balance 24-7,” Dr. Goulder said.

To see the study, you can click right here.

Kaelen Felix Illustrates a COVID-19 Article for 360 MAGAZINE

Antidepressant x COVID-19

Based on a trial from the University of Virginia School of Medicine, the antidepressant fluvoxamine appears to prevent COVID-19 infections from worsening, even keeping patients out of the hospital.

The clinical trial was conducted by the Washington University School of Medicine in St. Louis. Fluvoxamine was compared with a placebo in 152 adult patients who were infected with the coronavirus.

80 participants received the fluvoxamine, and not one of the 80 became seriously ill after 15 days. Six patients receiving the placebo became seriously ill with four being hospitalized for between four and 21 days. One of the four in the hospital was on a ventilator for 10 days.

Though the sample size was relatively small, the data is believed to be statistically significant. The plan is to launch a larger trial in coming weeks.

Eric J. Lenze, MD, of the Washington University School of Medicine, said patients who took fluvoxamine did not require hospitalization because of issues in lung function.

“Most investigational treatments for COVID-19 have been aimed at the very sickest patients, but it’s also important to find therapies that prevent patients from getting sick enough to require supplemental oxygen or to have to go to the hospital,” Lenze said. “Our study suggests fluvoxamine may help fill that niche.”

UVA’s Alban Gaultier, PhD, and former graduate student Dorian A. Rosen, PhD, found in 2019 that fluvoxamine may stop sepsis, a deadly inflammation causing the immune system to spiral out of control. The findings of Gaultier and Rosen inspired the tests at the Washington University School of Medicine.

Gaultier and Rosen determined that fluvoxamine reduces the production of cytokines, which have been linked to deadly cytokine storms, which are thought to occur in severe cases of COVID-19

“Because elevated cytokines levels have been associated with COVID-19 severity, testing fluvoxamine in a clinical trial made a lot of sense to us,” said Gaultier. “We are still unclear about the mode of action of fluvoxamine against SARS-CoV-2, but research is under way to find the answer.”

Washington University’s Angela M. Reiersen, MD, said the drug works by interacting with the sigma-1 receptor to reduce the production of inflammatory molecules.

“Past research has demonstrated that fluvoxamine can reduce inflammation in animal models of sepsis, and it may be doing something similar in our patients,” Reiersen said.

The limitations of the research were emphasized. The small sample size was noted along with the fact that 20% of participants stopped answering surveys during the trial. Though the researchers could rule out hospital visits for those who stopped answering, they did believe it possible that the participants sought treatment elsewhere.

Because of the limitations, the findings should be considered encouraging and worthy of further research rather than iron clad truth.

Gaultier said, “If a larger clinical trial (phase III) confirms the results, fluvoxamine would be a perfect treatment for COVID patients newly diagnosed. Fluvoxamine is not an experimental drug, it is cheap and safe and could be available as a first line of defense to unburden the hospitals that are overwhelmed by the COVID health crisis.”

For more medical research news from UVA, you can click right here.

Mina Tocalini, 360 Magazine, COVID-19

New Possible Key for Targeting Viruses

“Position 4” didn’t seem important until researchers took a long look at a particular peptide. That part of the peptide drawn from a SARS-CoV virus turned out to have an unexpected but significant influence on how it stably binds with a receptor central to the immune system’s ability to attack diseased cells. 

In a study published by the Proceedings of the National Academy of Sciences, researchers at Rice University’s Brown School of Engineering and the University of Texas MD Anderson Cancer Center revealed models at an atomic resolution that detail not only the binding but also, for the first time, the unbinding mechanisms that underlie a key component of the immune system. 

They say a better understanding of the entire mechanism could lead to advancements in immunotherapy that boost the body’s ability to fight disease. 

Rice computer scientist Lydia Kavraki, alumnus Jayvee Abella and postdoctoral researcher Dinler Antunes, led the study.

“Finding good targets to trigger a protective immune response is very challenging, especially in cancer research,” Antunes said. “The fact that this particular peptide was predicted not to bind to HLAs (human leukocyte antigens) by sequence-based methods highlights a blind spot in our current prediction capacity.”

“By incorporating structural analysis, we can detect the contribution of these secondary interactions to peptide binding and stability, hopefully enabling us to find better targets for antiviral vaccine development and T-cell-based cancer immunotherapy,” he said.

The researchers used their simulations to illuminate details of how the intracellular SARS peptide, QFKDNVILL, binds to an MHC receptor protein known as HLA-A24:02, primarily at dominant anchors on both ends of the peptide (at positions 2 and 9) and presents them for inspection to the immune system’s T cells. 

Stable binding of a peptide and MHC is a prerequisite to the activation of T cells, which look for peptides not normally found in healthy cells. If the peptide and protein don’t bind, the T cell is not prompted to attack. 

“That much was known from previous studies of the bound and unbound states of many such complexes,” Kavraki said. “What they didn’t capture was the intermediate states and the transitions that lead from one state to another, especially the unbinding.

“I think this is the only analysis that shows the unbinding of peptides from the MHC with atomic resolution,” Kavraki said. “Other peptides have similar characteristics and we think they would have similar behaviors.”

All of these interactions were revealed in great detail through Markov state models that analyze how systems change over time. In this case, the models revealed the importance of secondary sites that support the peptide’s primary anchors. That’s where position 4 stood out.

“There are the main, canonical anchors that people know, but there are these secondary interactions that contribute to the binding and the stability,” Antunes said. “These are harder to capture, but in this study, it seems that position 4 plays a very important role. When you mutate it, it affects the behavior of the peptide as it unbinds from the molecule.”

The researchers modeled mutations of the MHC to see how they would influence binding and found they supported the importance of position 4 to the stability of the complex.

“Our computational approach was able to make predictions on the effect of mutations that are then experimentally verified,” said co-author Cecilia Clementi, a former Rice professor who recently became Einstein Professor of Physics at the Free University of Berlin. 

The researchers developed a two-stage process to simplify the computational complexity of atom-scale analysis of large molecules. The first stage used a technique called umbrella sampling to accelerate the initial exploration of the molecules. The second, exploratory stage used adaptive sampling, in which simulations are driven to accelerate the construction of the Markov model.  

“The challenge is that these MHCs are pretty large systems for computational chemists to simulate,” said Abella, whose research on the topic formed much of his doctoral thesis. “We had to make some approximations and leverage advances in these classes of methods to move forward.”

“We’re not the first one to study unbinding, but what characterizes our work over others is that we keep full atomic resolution in our simulations,” he said. “Other works use a technique known as a Markov chain Monte Carlo, whereas we use molecular dynamics, which lets us incorporate time into our computation to capture the kinetics.”

Their methods can be applied to other peptide-MHC complexes with existing 3D models. “This was, in some sense, a feasibility study to show we can use molecular dynamics and build a Markov state model of a system this size,” Abella said. 

The researchers also noted the study’s relevance to the current fight against COVID-19, as the SARS peptide they viewed, QFKDNVILL, is highly similar to the NFKDQVILL peptide in SARS-CoV-2, with the same binding pockets in positions 2, 4 and 9.

“These results suggest that both peptides can bind to HLA-A*2402 and provide targets for anti-viral T-cell responses, which are of great interest in light of the current pandemic,” said co-author Gregory Lizée, a professor in the Department of Melanoma Medical Oncology at MD Anderson. “But these results also shed light on many other potential immune targets, including those of other viruses and even human cancers.”

Kavraki noted that experimental work by long-term collaborator Lizée and Kyle Jackson, a graduate research assistant at Lizée’s lab who produced the mutant proteins, were critical to validate their simulations. Kavraki’s own lab won a National Science Foundation (NSF) Rapid Response Research grant to help identify fragments of SARS-CoV-2 viral proteins as possible targets for vaccine development. 

Kavraki is the Noah Harding Professor of Computer Science and a professor of bioengineering, mechanical engineering and electrical and computer engineering. 

The Cancer Prevention and Research Institute of Texas, the Gulf Coast Consortia, the NSF, the Einstein Foundation Berlin and the Welch Foundation supported the research.

Pine-Sol x COVID-19

By Justin Lyons

The United States Environmental Protection Agency approved Pine-Sol Original Multi-Surface Cleaner to be added to a list of disinfectants proven to kill SARS-Cov-2.

According to a press release from The Clorox Company, a third-party testing company found that Pine-Sol killed SARS-Cov-2 on “hard non-porous surfaces” within ten minutes of contact.

The entire list of approved disinfectants, including many others from The Clorox Company, can be seen by clicking right here.

The key appears to be glycolic acid, as it is listed as an active ingredient in killing SARS-Cov-2 by the EPA and is listed in the ingredients for Pine-Sol Multi-Surface Cleaner by SmartLabel.

The press release pointed out that 58% of black millennial women are essential workers during the pandemic, putting them on the front lines and, therefore, at high risk of contracting the virus.

40% of black millennial women also expressed concern about access to disinfectants that kill SARS-Cov-2, while over 60% are concerned about keeping their families safe, keeping themselves safe and their financial stability.

While things like bleach, disinfectant wipes and Lysol sprays remain in high demand and difficult to find, Pine-Sol could help the fight against COVID-19 inside homes.

Chris Hyder, vice president and general manager of the cleaning division at The Clorox Company, looks at Pine-Sol’s availability as an important factor.

“With a long-standing history of being a powerful cleaner and disinfectant, and the trusted brand choice within the Black community, Pine-Sol® Original Multi-Surface Cleaner now offers the clean families have trusted through generations with the protection they need right now against the spread of SARS-Cov-2, the virus that causes COVID-19,” Hyder said. “We hope this new Pine-Sol® kill claim will increase access to disinfectants that can help prevent the spread of COVID-19.”

The Clorox Company’s press release also explained the most effective way to use Pine-Sol on household surfaces.

First, apply Pine-Sol with a clean sponge or cloth to the surface. Then, wet the surface and allow ten minutes to kill SARS-Cov-2 before finally rinsing area. The Clorox Company also advised removing excess dirt and dust with a pre-clean prior to using Pine-Sol.

The EPA’s list of approved disinfectants says additional products may be effective against SARS-Cov-2, and they will update their list as needed. They also advise following the directions on all product labels for safe and effective use.

It is possible that products not on the list could work against SARS-Cov-2 if it has an EPA registration number and lists human coronavirus as a target pathogen.