What is the difference between azivudine, monogravir and nematvir/ritonavir?💫💫💫

Azivudine, monogravir and nematvir/ritonavir are all clinical drugs used to treat the new coronavirus. What's the difference between them? 

What is the anti-coronavirus mechanism?

The new coronavirus is composed of RNA and protein. The raw material for RNA synthesis is cytosine nucleoside. Azivudine and monogravir are cytosine nucleoside analogs. They will synthesize poor RNA with the new coronavirus and inhibit the replication of the virus. Nematvir is a peptidomimetic substance. It will prevent the virus from synthesizing functional proteins by inhibiting 3C-like protease, and the replication of the virus will be inhibited. Although ritonavir has no effect against the new coronavirus, it will inhibit the elimination of nematvir and enhance its effect.

What are the properties of azivudine, monogravir and nematvir/ritonavir?

Due to their different chemical structures, they have different adverse reactions and metabolic processes in the body. 

Bone and Cartilage Toxicity: In trials, rats were repeatedly dosed with monogravir, which caused toxicity to the bones and cartilage of rats. Therefore, monogravir may affect bone and cartilage development in children.

Dosage in Patients with Hepatic or Renal Impairment: Monolavir is not eliminated primarily through the liver or kidneys, so no dose adjustment is required in patients with hepatic or renal impairment.

Drug interactions:

• Azivudine: Caution is required when combined with amiodarone, colchicine, dabigatran, digoxin, dronedarone, voriconazole, grapefruit juice, etc.
• Monolavir: Due to limited available data, no drug interactions have been found.
• Nematvir/ritonavir: These interact with many medicines.

What are the treatment differences between azivudine, monogravir, and nematvir/ritonavir?

Azivudine: It is mainly used to treat adult patients with characteristic pneumonia manifestations of new coronavirus infection visible on imaging (moderate infection). It is not intended for use in pregnant or breastfeeding women. If Azivudine is used, breastfeeding should be discontinued during treatment and for 4 days after treatment.

Monolavir: It is indicated for the treatment of adult patients with mild or moderate infections within five days of onset and who are at high risk for progression to severe disease. It has fetal toxicity similar to that of azivudine. If monogravir is used, breastfeeding should be discontinued during treatment and for 4 days after the end of treatment.

Nematrevir/ritonavir: Same indications as monogravir. However, it may still be used when the potential benefit to the mother outweighs the potential risk to the fetus. If nematvir/ritonavir is used, breastfeeding should be discontinued during treatment and for 7 days after the end of treatment.

What are the dosages of azivudine, monogravir, and nematvir/ritonavir?

Azivudine: If taken after meals, its absorption rate and total amount will be increased. Changes in drug concentration in the blood will also increase, thereby increasing the risk of adverse reactions. Its recommended usage is to take it orally once on an empty stomach before going to bed, 5mg each time (generally each tablet is 1mg, 5 pills taken orally each time), and the course of treatment should not exceed 14 days.

Monolavir: Take on an empty stomach or with food, once every 12 hours, 0.8g each time (usually 0.2g per tablet, 4 tablets taken orally each time) for 5 consecutive days.

Nematrevir/ritonavir: Take on an empty stomach or with food, once every 12 hours, 300 mg of nematvir (each tablet is 150 mg, 2 tablets taken orally each time) and 100 mg of ritonavir ( Each tablet is 100mg, 1 tablet taken orally at a time), taken continuously for 5 days.

What are the adverse reactions of azivudine, monogravir, and nematvir/ritonavir?

Azivudine: Common adverse reactions include diarrhea, increased transaminases, increased breathing, and occasionally increased the level of blood glucose. It may cause moderate to severe damage to the liver, so patients with moderate to severe liver damage should use it with caution.

Monolavir: Common adverse reactions include diarrhea, nausea, dizziness, and occasionally rash and urticaria.

Nematrevir/ritonavir: Common adverse reactions include diarrhea and taste problems, and occasionally elevated transaminases. It may cause severe liver damage and is therefore contraindicated in patients with severe hepatic impairment.

Additionally, they can affect fertility. Therefore, it recommends the use of effective contraception during and for 4 days after treatment with azivudine and monogravir, and the use of effective contraception during and for 7 days after treatment with nematvir/ritonavir.

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The impact of COVID-19 pneumonia on children may be seriously underestimated👪👪👪

Long-term symptoms of COVID-19 refer to a series of symptoms appearing after infection with COVID-19, including organ inflammation, shortness of breath, fatigue, behavior changes and so on. Studies have shown that about 30% of people infected with the COVID-19 will have long-term symptoms, even though most people can recover quickly. A recent study in the United Kingdom showed that only 4.4% of children with COVID-19 pneumonia will have symptoms for more than 4 weeks. Only 2% will last for more than 8 weeks. However, another study pointed out that 14% of 11 to 17-year-old children still have symptoms after 15 weeks. The child is older, the situation seems more serious.

Compared with adults, it is more difficult to diagnose long-term symptoms of COVID-19 pneumonia in children. Although most symptoms are similar between adults and children, it is just more difficult to detect. Experts believe that children's bodies have a lot of functional reserves. Therefore, if a 5-year-old child loses 20% of his physical functions, it is hard to find out. Some children with long-term symptoms of COVID-19 suffer from multisystem inflammatory syndrome in children (MIS-C), which may cause organ damage. There are also adolescents with long-term symptoms of COVID-19 who have developed Tourette's syndrome, which is characterized by convulsions and sometimes involuntarily cursing. These are very serious symptoms, not only for the children, but also for their family and related people around them will cause great mental stress. 

Risk and benefit balance

However, some experts believe that the benefit of unblocking is greater than that. They think that infections in children are not unacceptable because their symptoms are usually not serious. 

Without fully understanding the mechanism of this disease, and if its consequences may not slowly appear until many years later, it seems a bit reckless to risk the children. Although it is necessary of reopening the economy, it should adopt certain simple measures, such as wearing masks in schools and enhancing ventilation. Taking these measures can effectively protect the next generation. 

Protect the children from COVID-19

The risk of long-term symptoms of COVID-19 does exist. Schools should improve their preventive measures to protect their students from infecting the COVID-19 virus. It is recommended to provide vaccines to all suitable children. It is not mandatory. Their parents can choose if their children received the vaccines. Doctors need to recognize the severity of the long-term symptoms of COVID-19, rather than just treating it as a psychological problem and asking patients to see a psychologist. This is a physiological problem, so there must be some methods of physiological solution. People often ignore related issues. 

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The COVID-19 epidemic is far from over😷😷😷

Recently, the counter-attack of COVID-19 epidemic will cause schools to be forced to close and classes to be suspended. People received the COVID-19 vaccine will still face a new round of infection. When the hospital is overwhelmed again, office workers will also weigh whether they need to continue working at home. 
Scientists believe that before the end of COVID-19 epidemic, almost everyone has either been infected with the COVID-19 virus or vaccinated with the COVID-19 vaccine or maybe both. A few unlucky people may be infected with COVID-19 more than once. Before all human beings are infected with the virus, the race between the virus mutation and vaccination will not end.
Dr. Michael Osterholm, American Covid-19 consultant, he said that the cases around the world continue to rise and then decline. It may be a sharp decline. However, he think it is likely that there will be a sharp rise again in the autumn and winter of this year. There are still billions of people in the world who have not been vaccinated and there is currently very little chance of eradicating the virus. Then, as the economy reopens, it is expected that more new cases will appear in public transportation, workplaces  schools in the coming months. Even if the immunization rate rises, there will still be people who are vulnerable to COVID-19: newborns, people who are unable or unwilling to receive the vaccine and people have been vaccinated with the vaccine but have breakthrough infections because of the reduced protection of the vaccine. 

COVID-19 vs. Other epidemics

An Epidemiologist pointed out that there were 5 well-documented epidemics in the past 130 years, they provide some inspiration for the future development of COVID-19 epidemic. Although the longest global flu has lasted for five years, the average cycle is two to three years with two to four rounds of infection. However, COVID-19 may not follow the development pattern of past epidemics. This is a new type of pathogen that is potentially more infectious. So far, the death toll from the new crown epidemic has exceeded 4.7 million. Vaccination can effectively reduce the rate of severe illness and mortality.  The vaccination rate continues to increase, but the rise in infection means that the virus is infecting teenagers and other people who have not been vaccinated. It is leading to an increase in the rate of severe illness in these groups. Countries with low COVID-19 vaccination rates are facing the largest outbreak so far due to the emergence of the delta variant strain. With the delta variant strains raging in many countries, another new variant strain is likely to emerge.

Experience has shown that people usually think that the pathogenicity of the virus will diminish over time, so that all hosts will not be completely wiped out, but this idea is not correct. Although the pathogenicity of new mutant strains is not necessarily more serious, as the virus is constantly adapting to new hosts during the epidemic. Its fatality rate may actually be higher.

Some researchers said that the new coronavirus may be completely resistant to the first-generation new coronavirus vaccine. As the virus continues to evolve, we may need to be vaccinated regularly to effectively deal with the new coronavirus just like preventing the flu.

When will the COVID-19 epidemic end?

Experts generally believe that only when most people (approximately 90% to 95% of the global population) have gained a certain degree of immunity through COVID-19 vaccination or infection, the current epidemic can be controlled. They believe that the key to controlling the epidemic should be the vaccination of COVID-19 vaccine. If people are not vaccinated, the virus may spread widely in the autumn and winter of this year and almost everyone will be infected by that time. 

An associate professor of medical history at Oxford University believes that the end of the COVID-19 epidemic will vary in different regions, just like the time of the outbreak. Governments will have to make decisions about the extent to which they can tolerate coexistence with the virus. The response measures taken vary greatly. Although some countries strive to achieve zero cases of COVID-19, it is unlikely that the world will completely eradicate the virus.

🔑We must remain alert and treat the COVID-19 epidemic with caution. If anyone thinks that we will be able to resolve the pandemic in the next few days or months, that would be a big mistake.

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Inventory of various new discoveries of metformin😎😎😎

Metformin is an anti-diabetic drug and a classic oral hypoglycemic agent. Since its inception in 1957, it has been used clinically for more than 60 years. It is currently one of the most widely used oral hypoglycemic drugs in the world. Even though there are many new hypoglycemic drugs, metformin is still the primary drug for type 2 diabetes.

Metformin was born in 1929 and originated from galega officinalis. In 1957, French diabetologist professor Jean Sterne first used metformin for clinical hypoglycemic reduction. Then its application value is still being discovered. Let us take a look at what new discoveries have been made recently.

1. Cancer

Acidic phospholipids play an important role in regulating electrostatic membrane association of programmed cell death ligand 1 cytoplasmic domain (PD-L1-CD). Metformin can competitively dissociate PD-L1-CD from the membrane and affect the stability of PD-L1. This revealed that the molecular mechanism of metformin's anti-tumor effect and provided new ideas for related immunotherapy targeting PD-L1.

There are many studies that supporting metformin can decrease the risk or improve the symptoms of cancer patients. Such as esophageal squamous cell cancer, pancreatic cancer, primary bone cancer.

2. Obstetrics & Gynecology

a. Improve neonatal obesity

    Metformin has many benefits for mother's blood glucose and neonatal obesity, including improved blood glucose, reduced caesarean section, reduced mother's weight, lower insulin requirements,  lower birth weight and obesity measurements of newborns.

b. Prevent adverse pregnancy outcomes in patients with polycystic ovary syndrome

    Metformin can prevent late period abortion and premature birth in women with polycystic ovary syndrome.

3. Metabolic diseases

Metformin can improve the metabolic status of patients treated with systemic glucocorticoids. It can not only reverse the metabolic complications caused by the use of systemic glucocorticoids, but also reserve the anti-inflammatory effects of glucocorticoids. It benefits many patients taking systemic glucocorticoids.

4. Cardiovascular System

 a. Heart failure

    Non-diabetic heart failure patients with reduced ejection fraction (HFrEF) use metformin to reduce myocardial oxygen consumption and improve myocardial efficiency.

b. Left ventricular hypertrophy

    Metformin treatment significantly reduced the left ventricular mass index. Patients taking metformin reduced left ventricular thickening by two time less. In addition, metformin also reduced blood pressure, oxidative stress, and weight. Metformin has the potential to improve cardiovascular health.

c. Air-pollution-induced thrombosis

    Atmospheric particulate matter can induce alveolar macrophages to release pro-inflammatory factors including interleukin 6 (IL-6), leading to arterial thrombosis and death.

    Metformin blocks the mitochondrial electron transport and inhibits the production of reactive oxygen species, thereby blocking the release of IL-6 and inhibiting the formation of arterial thrombosis. This confirms that metformin can be used as a potential therapeutic drug to prevent cardiovascular diseases caused by air pollution.

5. Nervous system

a. Cognitive and nerve recovery after brain tumor surgery

    For children with brain tumor patients who have received craniocerebral radiotherapy, metformin can significantly improve their statement memory and working memory function, repairing white matter damage. Metformin is also safe and tolerable in this population.

b. Multiple Sclerosis

    After treatment with metformin, oligodendrocyte precursor cells can restore their response to the signal of promoting-differentiation, promote the regeneration of nerve myelin. This is useful for the treatment of central nerve demyelination such as multiple sclerosis.

c. Cognitive decline and dementia

    Patients with type 2 diabetes who take metformin have slower cognitive decline and a lower risk of dementia.

6. Locomotor system

a. Osteoarthritis

    Metformin can prevent the occurrence and development of osteoarthritis, alleviate the pain sensitivity associated with osteoarthritis in mice. Its protective effect on cartilage is mainly through the activation of AMPK signals.

b. Intervertebral disc degenerative disease

    Metformin can promote the release of small extracellular vesicles of mesenchymal stem cells, increase the level of proteins that regulate cell proliferation in the vesicles, and can optimize the application effect of extracellular vesicles in the regeneration and repair of intervertebral discs.

7. Digestive system

Metformin stimulates bile secretion in the intact liver, but this drug can also cause severe damage to bile acid secretion.

8. Infection

a. COVID-19

   Metformin inhibits the activation of NLRP3 inflammasomes and the production of IL-1β in cultured macrophages and alveolar macrophages, as well as the secretion of inflammasome-independent IL-6, thereby attenuating lipopolysaccharide and COVID-19 induced acute respiratory distress syndrome. Metformin can be a potential treatment for severely patients with COVID-19 and other induced acute respiratory distress syndrome.

b. HIV

    Metformin reacted on mitochondrial respiratory chain complex-I and inhibit the oxidative phosphorylation (OXPHOS) pathway. It inhibited the replication of human CD4⁺ T cells and HIV-1 virus in humanized mouse models. It revealed that metformin and others OXPHOS pathway inhibitors may be an adjunct to treat AIDS.

👉Metformin has also anti-aging effect. Most effects still are at the research stage and may not be used on treatment. Therefore, metformin still deserves more in depth research.

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Is the COVID-19 drug better than vaccine??? 😲😲😲

On October 1st, Merck and Ridgeback Biotherapeutics reported the results from their COVID-19 drug Molnupiravir from phase 3 study in patients with mild to moderate COVID-19. 

In their study, the risk of hospitalization or death are reduced by about 50%. Only 7.3% patients who got Molnupiravir were either hospitalized or died during the research. And the placebo group is 14.1%. The Molnupiravir group is no one dead and the placebo group is reported 8 people dead. 

But after a few days of that announcement, a source with the drug controller general of India reported that Molnupiravir is no significant efficacy toward the moderate COVID-19 and that effective effect is only against the mild COVID-19.

Although Merck said that no significant safety issues have been observed in the study, some scientists have expressed doubts about the safety of Molnupiravir. The structure of Molnupiravir is similar to the nucleotide of RNA. That makes the virus produce ineffective RNA to stop virus replication. Those scientists believe that this function will have adverse effects on the human too.

So, is the COVID-19 drug better than vaccine?

It is hard to say which one is better. The vaccine is always being the first way for diseases. It can protect people to avoid getting sick. The treated drugs will be used when the people get sick. Therefore, we should not compare with drug and vaccine. You can think that they are two different things.

Although Molnupiravir is highly cheaper than other COVID-19 treatment methods, it is still much more expensive than the widely vaccinated COVID-19 vaccine.

As the first oral small molecule antiviral drug supported by clinical data, Molnupiravir has obvious advantages over the current neutralizing antibody treatment of COVID-19: 

1. It does not require low-temperature storage and transportation.

2. It can be taken orally.

3. It provides a life defense for people who cannot or refuse to receive the COVID-19 vaccine.

The convenience and price of Molnupiravir make it more approachable for the early-stage patients or high-risk groups.

The FDA will discuss for an emergency es authorization for Molnupiravir to treat COVID-19 on 30th November 2021. Let's look forward about it.

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