The most "strong" mutant strain "Mu" is here!

Author: Good Lentils

The new coronavirus has discovered a new strain again!

On September 1, the World Health Organization announced that due to the recent strong momentum of the "MU" strain, it was included in the "variants of interest" list
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It is reported that "MU" was discovered in January this year, but in the past half a year, it has invaded more than 40 countries.
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Variant strains of the new crown are coming fiercely, and currently there is only one drug called "Remdesivir" in the world, which has been approved for marketing as a new crown therapeutic drug
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A few days ago, the Ministry of Science and Technology issued the "Guidelines for the Application of Small Molecule Novel Coronavirus Drug R&D Emergency Projects", and specific drugs are imminent
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From Alpha to Lambda, are you really helpless in the face of "cunning and changeable" mutant strains?

There will never be a new crown special medicine?

At present, 8 vaccines have been approved for marketing globally, 10 vaccines are in clinical phase III, and 6 vaccines are in clinical phase II
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However, the current situation of the global epidemic situation still shows the characteristics of low vaccination rate, continuous virus mutation, and low effective protection rate of vaccines
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Therapeutic drugs, especially specific treatments, will become the last line of defense for human life and health
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At present, only Remdesivir has been approved as a new crown therapeutic drug in the world, but its clinical efficacy has been questioned
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The global R&D pipeline continues to expand, and major pharmaceutical companies have their own magical powers; neutralizing antibodies, small-molecule chemicals, Chinese patent medicines, Chinese medicine prescriptions.
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Hundreds of people compete for the flow
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Drug development is full of uncertainty, and the road to the development of new crown specific drugs is already full of "corpses":

Oseltamivir, hydroxychloroquine, remdesivir, lopinavir/ritonavir, beta interferon, etc.
have been eliminated one after another
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Takeda Pharmaceuticals, Regeneron, Sanofi, Roche, AstraZeneca, etc.
have all succumbed to the new crown "special medicine" field
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The WHO even gave a pessimistic warning: there may never be a new crown drug
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However, the magic of nature is that there is always an invisible hand balancing the entire ecosystem
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In the process of hundreds of millions of years of evolution, the mutual growth and mutual restraint relationship of our ecosystem has developed extremely complete
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The natural enemy of the new crown virus is likely to be left behind by nature, that is, there may be a "natural nemesis" in natural medicine
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Natural medicine, gift of nature

Natural products are a treasure trove of drug development
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"Nature Chemistry" review article analysis data shows that since 1939, a considerable number of drugs approved by the US FDA for marketing contain natural product fragments
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Image source: Nature Chemistry

The following are the notes on a and b in the figure
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a.
Natural product medicinal fragments
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b.
The average number of natural product fragments in the marketed drugs each year
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A recent review reported that approximately 36% of the drugs marketed between 1981 and 2019 were derived directly or indirectly from natural products

Several classic stories about natural medicine fighting the virus have far-reaching influence so far, and I hope they can be inspired

Malaria is one of the oldest diseases of mankind, and it is still an important public health problem of global concern and urgently to be solved

Humans have been searching for a specific therapeutic drug for Plasmodium falciparum for hundreds of years

China's 523 mission has focused global attention on China

The team led by Professor Tu Youyou took the lead in discovering artemisinin, and carrying out structural determination, clinical verification and optimization, and was subsequently hailed by the international medical community as the "nemesis" of drug-resistant malaria

With the gradual deepening of research on artemisinin and its derivatives, its efficacy in anti-inflammatory and immune regulation has been gradually discovered, and it has been proven to have a good effect in a variety of disease models

In addition, studies have confirmed that artemisinin compounds have inhibitory effects on herpes viruses such as cytomegalovirus, hepatitis B virus, hepatitis C virus, pseudorabies virus and other viruses

This is one of the most representative cases in natural medicine discovery
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In addition, avian influenza also made the legend of shikimic acid
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From 2004 to 2005, the bird flu swept the world, and everyone heard of it
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Fortunately, people discovered that star anise preparation contains an important medicinal ingredient-shikimic acid, which is an important ingredient of the anti-H5N1 avian influenza virus drug "Tamiflu"
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Shikimic acid was once a weapon against bird flu
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2009 was also an uneasy year for Tamiflu, because this year, influenza A (H1N1) became the key word of the year
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According to the recommendations of the Ministry of Health and the World Health Organization, Tamiflu is the preferred western medicine for anti-A influenza
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In this protracted war against the influenza virus, Tamiflu once again established its status as the "one brother" in the fight against the influenza virus
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The story of natural medicine is not over yet.
Among the new coronavirus specific medicines, is it possible for natural medicines to reappear brilliantly?

Three key points in the development of natural medicines

Let's review several key technical nodes in the development of natural medicines
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(1) Natural products as the starting point for lead compounds

In the protracted challenge of new drug discovery, current medicinal chemistry gradually abandons simple planar molecular structures, and instead emphasizes three-dimensional design.
The unique structure of natural products serves as a reference
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The rise of fragment-based drug discovery, bypassing the toxicity and lack of effectiveness in early drug discovery, and with the help of biophysical technology and ligand screening, the molecular structure is gradually linked and increased to develop Become a lead compound with biological activity
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(2) Computer-aided design

Natural products have inspired inspiration, and computer programs have increased the efficiency of rationally designing molecules
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The molecular framework or framework acts as a bridge to connect the two worlds of natural products and synthetic compounds
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The core of computer software is to visualize natural products and synthetic compounds, and to generate a skeleton tree through gradual simplification to obtain an intuitive structure diagram
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Compared with high-throughput screening, this method has a higher hit rate
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However, the activity of compounds obtained through molecular design based on natural product fragments is often only weak to moderate, and subsequent further structural optimization is an indispensable step to improve the activity
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(3) Predict the macromolecular targets of natural products

The lack of precise information on natural product targets once hindered the design of molecular skeletons in medicinal chemistry and drug discovery.
Now there are many innovative target prediction tools that can help determine biological macromolecular targets or potential drug off-target effects.
, May help determine the biological activity of natural products
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Target prediction can guide the biochemical screening of natural products to reduce the number of experiments and save valuable resources
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Figure 2 Target prediction and structure analysis of natural products and synthetic biologically active molecules

Image source: Nature Chemistry

Tools such as modern chemistry and bioinformatics have promoted drug development based on natural products, such as target prediction software, natural product metabolite research, pharmacophore kinetics and thermodynamics to help discover leading compounds from natural products, and realize The transformation from structure to fragment and then to structure
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Time waits for no one, is there no shortcut to develop new anti-coronavirus drugs? Yes, the most effective shortcut is to screen out potentially effective drugs from natural drugs
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The screening and development of natural medicines are likely to break through our existing cognition.
Whether in terms of target binding or mechanism of action, natural medicines have a variety of core structures, which can broaden the screening library
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Just like natural evolution, if the sample size is large enough, nature will find the seeds of evolution
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Whether natural medicine may become the winner of the new crown special medicine, we will wait and see!