More natural cures for COVID-19 validated

•Green tea, olive oil, and red wine block major coronavirus enzyme
•Just 150 minutes of moderate exercise weekly lower the risk of catching the virus
•Researchers assess the cytoprotective activity of nicotine against pandemic
•Lovemaking can boost heart, clear stuffy nose, fight off COVID-19

Scientists have validated more natural cures for the prevention and treatment of COVID-19.

They found that natural compounds in green tea, olive oil and red wine block major coronavirus enzyme; just 150 minutes of moderate exercise weekly lower the risk of catching coronavirus; consumption of ultra-processed foods associated with severe viral infection; demonstrated cytoprotective activity of nicotine against pandemic; and lovemaking can boost heart, clear stuffy nose and fight off COVID-19.

Cytoprotection is a process by which chemical compounds provide protection to cells against harmful agents.

Indeed, three natural compounds present in foods like green tea, olive oil and red wine are promising candidates for the development of drugs against the coronavirus.

In a comprehensive screening of a large library of natural substances at DESY’s X-ray source PETRA III the compounds are bound to a central enzyme vital for the replication of the coronavirus.

Deutsches Elektronen-Synchrotron (DESY), a Research Centre of the Helmholtz Association, is located in Hamburg, Germany. PETRA III, which took up operation in 2009, is the most brilliant storage-ring-based X-ray radiation source in the world.

As the most powerful light source of its kind, it offers scientists outstanding experimental opportunities with X-rays of exceptionally high brilliance. In particular, this benefits researcher investigating very small samples or those requiring tightly collimated and very short-wavelength X-rays for their experiments.

All three compounds are already used as active substances in existing drugs, as the team headed by Christian Betzel from the University of Hamburg and Alke Meents from DESY reports in the journal Communications Biology. However, if and when a coronavirus drug can be developed on the basis of these compounds remain to be investigated.

Study’s main author, Vasundara Srinivasan, from the University of Hamburg, said: “We tested 500 substances from the Karachi Library of Natural Compounds if they bind to the papain-like protease of the novel coronavirus, which is one of the main targets for an antiviral drug. A compound that binds to the enzyme at the right place can stop it from working.”

The papain-like protease (PLpro) is a vital enzyme for virus replication: When a cell is hijacked by the coronavirus, it is forced to produce building blocks for new virus particles. These proteins are manufactured as a long string. PLpro then acts like a molecular pair of scissors, cutting the proteins from the string. If this process is blocked, the proteins cannot assemble new virus particles.

Srinivasan said: “However, PLpro has another vital function for the virus. It blocks a protein of the immune system, called ISG15, and that severely weakens the cell’s self-defense. With inhibiting PLpro, we can also enhance the cell’s immune response.”

For the experiments, PLpro was mixed with each of the 500 natural substances in a solution, giving them the chance to bind to the enzyme. It is not possible to see if a substance binds to the enzyme with a conventional light microscope. Instead, tiny crystals were grown from the mixtures. When illuminated with the bright X-rays from PETRA III at the experimental station P11, the crystals produced a characteristic diffraction pattern from which the structure of the enzyme can be reconstructed down to the level of individual atoms.

Meents explained: “From this information, we can produce 3-dimensional models of the enzyme with atomic resolution and see if and where a substance binds to it.”

The screening showed that three phenols bind to the enzyme: hydroxymethyl phenol (YRL), isolated for the experiments from the henna tree Lawsonia alba, which is a compound present in many foods such as red wine and virgin olive oil and used as an anti-arrhythmia agent.

Hydroxybenzaldehyde (HBA) is a known anti-tumour agent and accelerates wound healing. It was isolated from the copperleaf Acalypha torta. Methyldihydroxybenzoate (HE9), isolated from the French marigold Tagetes patula, is an anti-oxidant with an anti-inflammatory effect and is found in green tea.

In subsequent lab tests, established and performed by Hévila Brognaro in Betzel’s group, the three phenols reduced PLpro’s activity by 50 to 70 per cent in living cells.

“The advantage of these substances is their proven safety,” said Betzel, who is also a member of the cluster of excellence CUI: Advanced Imaging of Matter. “These compounds naturally occur in many foods. However, drinking green tea will not cure your corona infection! Like it will not heal your wounds or cure your cancer. If and how a corona drug can be developed from these phenols is subject to further studies.”

In a different screening, a team consisting largely of the same scientists had already screened thousands of existing drugs at PETRA III as possible inhibitors of the coronavirus’ main protease (Mpro), also a molecular pair of scissors and a main potential drug target.

The screening identified several corona drug candidates, and the most promising have entered preclinical testing. “The corona initiative from DESY and University of Hamburg is one of the very few worldwide that investigated both of COVID-19’s main targets,” Betzel said.

In the new study, scientists from the University of Hamburg, the University of Sao Paulo in Brazil, Diamond Light Source in the United Kingdom, European XFEL, Bahauddin Zakariya University in Pakistan, Hospital Israelita Albert Einstein in Brazil, Scientific Platform Pasteur in Brazil, the European Molecular Biology Laboratory in Hamburg, Fraunhofer Institute for Translational Medicine and Pharmacology in Hamburg, Jozef Stefan Institute in Slovenia, Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins in Slovenia, the University of Greifswald and DESY contributed to the work.

Also, a major review suggests regular exercise may lower the risk of catching COVID-19.

Physical activity has long been known to reduce the chance of severe illness by strengthening the immune system.

But researchers now believe keeping fit can help ward off the infection altogether after analysing more than a dozen international studies.

They found that 150 minutes or more of moderate exercises, such as brisk walking or dancing, reduced the risk of a COVID-19 infection by 11 per cent.

The same protective effect was seen in people who did 75-plus minutes of vigorous exercise a week, including running, swimming or sports like football and rugby.

People who regularly exercised were also up to 43 per cent less likely to die or fall seriously ill from the virus than their peers.

Researchers said the findings could help guide “a public health strategy”, that would include encouraging more regular exercise.

They believe working out more regularly helps the body fight off the infection before it penetrates the body by increasing white blood cell and antibody counts.

The latest research, published in the British Journal of Sports Medicine, looked at 16 studies carried out in South Korea, Iran, Canada, the United Kingdom (UK), Spain, Brazil, Palestine, South Africa and Sweden.

Studies dated from November 2019 to March 2022, encompassing the very first COVID-19 cases in Wuhan, China, up to the Omicron variant.

Only studies that used Polymerase Chain Reaction (PCR) tests and had exercise data were included. In total, more than 1.8 million participants were involved in the research.

Physical activity levels were recorded either through self-reported questionnaires or figures from wearing heart rate monitors and other activity-tracking devices.

Most of the studies controlled for other factors, such as smoking or obesity, that could affect COVID-19 infection, although “the adjustment for covariates of some individual studies could have been not sufficient”, the authors said.

Overall, the studies showed exercising regularly reduced the risk of infection by 11 per cent and serious illness — defined as needing intensive care or a ventilator — by 34 per cent.

Exercise also reduced the chance of hospitalisation of any kind by 36 per cent and death by 43 per cent.

The researchers, led by Yasmin Ezzatvar, a nurse at the University of Valencia, said the results showed how well exercise protects against COVID-19.

Writing in the paper, the authors said: “Regular physical activity seems to be related to a lower likelihood of adverse COVID-19 outcomes.

“Our findings highlight the protective effects of engaging in sufficient physical activity as a public health strategy, with potential benefits to reduce the risk of severe COVID-19.”

They said exercise could help reduce the chance of getting severe COVID-19 by reducing the chance of getting diabetes, obesity and high blood pressure. All three conditions have been linked with reacting more strongly to the virus.

Little is known about why exercise limits the chances of actually catching the virus, but the experts suggested it could help increase the body’s immune defence.

Previous research has shown exercise helps the body produce more antibodies and white blood cells, which are vital in the body’s response to infection.

Physical activity also reduces the release of the stress hormone cortisol, which can reduce the number of disease-fighting white blood cells produced in the body.

Meanwhile, the rapid transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of the COVID-19 pandemic, has immensely affected the global healthcare sector and economy. Additionally, the incidence of long COVID, which involves the persistence of symptoms for more than three months, has significantly affected millions of individuals.

Several COVID-19 vaccines, therapeutics, and non-pharmaceutical strategies have been designed to manage the ongoing pandemic. Nevertheless, a better understanding of the risk factors associated with SARS-CoV-2 infection would help protect individuals from contracting the infection in the future.

Nutrition is the key source of energy and is considered to be a major determinant of human health. A balanced diet is associated with maintaining a healthy gut microbiome, which is an important factor that regulates the immune system.

According to a recent study, individuals who consume greater amounts of fruits and vegetables, as well as a healthy plant-based diet, are at a lower risk of COVID-19. This observation indicates a potential link between diet and COVID-19.

Based on the extent and purpose of industrial processing, food-based products have been categorised into four groups by the NOVA classification system. Of these four groups, ultra-processed foods (UPFs) consist of industrial formulations of processed food substances, such as fats, oils, starch, sugar, and protein isolates. These food products are subjected to hydrogenation, hydrolysis, or other chemical modifications by the addition of colorings, flavourings, and emulsions.

Typically, UPFs contain high levels of saturated fats, sugars, trans fats, and salt. Additionally, these products contain a low amount of protein, dietary fibre, vitamins, and minerals.

Several studies have indicated that UPFs are a primary dietary source of food adulterants and neo-formed compounds, which may alter the composition of the gut microbiota and increase the risk of inflammation.

Individuals heavily dependent on a UPF-rich diet often suffer from mineral and vitamin deficiencies, experience damage to the immune system, and are highly susceptible to infections. UPFs are associated with an increased risk of inflammatory bowel disease, cardiovascular disease, and cancer.

Scientists have noted a scarcity of evidence related to the relationship between UPF consumption and the risk of COVID-19. Considering this gap in research, a recent European Journal of Nutrition study explored the association between UPF consumption and the risk of SARS-CoV-2 infection.

The current study used data from the United Kingdom Biobank, which is a prospective cohort containing about half a million participants from 22 assessment centres across Scotland, Wales, and England. All study participants were between 40 and 69 years of age. A total of 41,012 participants from the U.K. Biobank were considered in this study.

To assess the dietary intake of the participants in the previous 24 hours, scientists used the Oxford WebQ dietary questionnaire. This questionnaire included 206 types of food, along with their quantities and 32 types of drinks.

For the 24 hours dietary assessment, the online dietary questionnaire was recalled a minimum of two times and a maximum of five times. The current study measured the association between UPF consumption, as indicated by the percent daily gram intake, and SARS-CoV-2 infection using a multivariable logistic regression that was adjusted for potential confounders.

A strong relationship between UPF consumption and increased risk of COVID-19 was observed. This association was consistent in varied sub-groups based on age, comorbidity status, and educational level.

Although the association between UPF consumption and COVID-19 was partially mediated by body mass index (BMI), a direct effect of UPF weight ratio on the risk of COVID-19 was established.

Some of the mechanisms that link UPF intake and increased risk of COVID-19 include enhanced levels of sugars and trans-fat, which stimulates pro-inflammatory effects. This condition could adversely affect the synthesis and function of immune cells.

Additionally, UPFs contain high saturated fats and reduced fibres, which might lead to chronic activation of the innate immune system and suppression of the adaptive immune system. The chemical additives of UPFs also adversely affect human health. Furthermore, a UPF-rich diet may cause vitamin and mineral deficiencies that could significantly affect the human immune system.

Body Mass Index (BMI) was found to be a partial mediator that influenced the association between UPF and COVID-19. A significant increase in UPF consumption occurred during the COVID-19 lockdown, which might have affected people’s immunity, thus making them more susceptible to the infection.

The current study is the first to explore the relationship between UPF consumption and the risk of SARS-CoV-2 infection. This large prospective cohort study revealed that an UPF-rich diet was associated with a significantly increased risk of COVID-19. Therefore, a healthy diet with reduced UPF intake has been recommended to protect individuals from severe clinical outcomes.

Meanwhile, in a recent study published in the PLoS ONE journal, researchers assessed the cytoprotective activity of nicotine against coronavirus disease 2019 (COVID-19).

In the present study, the researchers performed cytotoxicity assays to assess the potential cytoprotective activity displayed by nicotine against COVID-19.

The team utilised virus strains including SARS-CoV-2, USA WA 01/2020, and CSU V3 3/17/2020 for this study, and the cell line Vero E6 was employed for the plaque reduction assay. The cytotoxicity assay was performed by testing nicotine at different concentrations such as 0.005, 0.01, 0.05, 0.1, 0.5, 1, 5, 10 μM. This wide range of concentrations ensured that plasma nicotine levels reported in smokers were also included in the assay. Cytotoxicity was estimated with the alamar blue reagent, while cytoprotection and cell viability were assessed after staining with acridine orange (AO)/ propidium iodide (PI).

Cytotoxicity tests were performed on the activity of nicotine against SARS-CoV-2 in Vero E6 cells. Cytoprotection was evaluated as cell death in comparison to the live cell count. Cell death was calculated as per the number of cells that were stained with PI while the number of live cells was estimated as per AO staining. Furthermore, the team determined if nicotine was active in the assessed cell growth media and the cell culture condition using two per cent Dulbecco’s modified eagle medium (DMEM) comprising 2mM L-glutamine by exposing A549 lung cancer cells to nicotine or the vehicle control.

The study findings showed that none of the nicotine concentrations provided sufficient cytoprotection against COVID-19 in Vero E6 cells. Additionally, compared to the media control sample comprising DMEM, the team found no cytotoxicity in the nicotine treatment.

Notably, nicotine elicited Erk1/2 (extracellular signal‑regulated protein kinase) phosphorylation in A549 cells. This indicated that nicotine showed significant activity in the DMEM cell culture.

The study findings showed that even in the presence of high concentrations of nicotine, there was no considerable cytoprotective activity induced against COVID-19 while nicotine at 2 μM to 10 μM in the control media displayed normal activity of Erk phosphorylation.

The researchers believe that future studies could determine the activity of nicotine against SARS-CoV-2 in other cell lines.

Also, researchers have demonstrated why sex twice a week is the magic medicine: Lovemaking can boost one’s heart, clear a stuffy nose, and even fight off COVID-19. An active sex life can help reduce the risk of heart disease and incontinence. Sexual activity least three times a month is linked to a milder COVID-19 infection. Another study found an orgasm cleared a stuffy nose as well as a nasal spray.

Latest studies showed an active sex life could be as important as watching one’s diet, moderating alcohol intake and quitting smoking to boost health.

Research shows that it can help reduce the risk of heart disease and incontinence.

And last year, a study published in the journal Fertility and Sterility showed that sexual activity at least three times a month was linked with a milder COVID-19 infection.

The theory is that it primes the body to handle pathogens more effectively.

This followed a 2004 study in the journal Psychological Reports which found that intercourse once or twice a week increases levels of immunoglobulin A, part of the antibody response of the immune system that defends us against infection.

Another study suggested that orgasms can clear a stuffed-up nose as effectively as a nasal spray, reported the journal Ear, Nose & Throat last year — probably because exercise has also been shown to be a decongestant, as the resulting increase in body temperature loosens mucus while the increase in circulation encourages the flow of nasal discharge.

And research from University College London found that women engaging in sexual activity at least monthly had a later menopause than those who weren’t sexually active.

The researchers suggest that if sexual activity is not detected, the body deprioritises ovulation, triggering the menopause.

It can also be good for mental health. A study in The Journal of Sexual Medicine in January found that people who maintained a sexual relationship during lockdown — whether they were living with their partner or not — were 34 per cent less likely to experience depression than those who didn’t.

In fact, some experts believe sex to be such an important barometer of general health that it should be more widely discussed by doctors with their patients — yet this rarely happens.

An inability to get an erection can have a number of causes but may occur as a result of blockages in the arteries supplying the penis, a potential sign of furred arteries elsewhere in the body.

Being physically able to have sex also indicates a certain level of fitness.

When having sex, men burned on average 100 calories and their heart rate rose to as much as 170 beats per minute — this helps strengthen the heart — according to research published in the Archives of Sexual Behaviour in February.

Men having sex two to three times a week have a 45 per cent lower risk of a heart attack compared with those having sex once a month or less, reported the American Journal of Cardiology in 2010.

The physical exertion is thought to help explain why it might improve immunity — specifically raising levels of immunoglobulin A, which exercise has also been shown to improve.

A 2016 study from Harvard University, published in the journal European Urology, found that ejaculating more than 20 times per month reduced prostate cancer risk by 20 per cent for men aged 20 to 50 — the theory being that it “flushes the system.”