This article comes from Yiou.com (ID: i-yiou) , original title “America’s first new crown rehabilitation of patients with pneumonia, an exclusive interview with Transocean propaganda” cure “the Chinese scientist”, author: Lin Yi Ling

Redesivir is currently the only effective and safe drug for the Wuhan epidemic, and urges the Chinese government to negotiate with Gilead as soon as possible.

In the evening of the 31st, along with the Shanghai Institute of Materia Medica and the Wuhan Institute of Virology of the Chinese Academy of Sciences, the Chinese patent Shuanghuanglian oral solution could inhibit the new coronavirus. (2019-nCoV ) ‘s news detonated the network, Shuanghuanglian oral solution was sold out of the network overnight. After the “farce”, the Shanghai Medical Institute came out in the early morning on the 1st and responded: “We don’t want to go overboard with scientific things.”

Compared with the heat caused by today’s Shuanghuanglian oral solution, Gilead, who had only lived in the mouths of some experts at home and abroad, is in the process of studying Ebola and MERS-CoV, a nucleotide analog prodrug of ridicvir < span class = "text-remarks" label = "Remarks"> (Remdesivir) , it is not so “good luck”. At that time, Redecive seemed to these experts to be useful for the treatment of new crown virus, but it was far from “outside the world”.

On the 29th, he published “Yi ShiFor the sake of reference: author of the new emergency coronavirus 2019-nCov infection-induced emergency prevention and treatment strategy for acute respiratory infections “, Liu Wenshe, director of the Texas A & M Drug Search Center, accepted an exclusive interview with EurHealth.

In the interview, he mentioned that when he wrote his dissertation on the 25th, he came to the conclusion that Redecive was basically the only effective and safe drug that can be used in the Wuhan epidemic. He called on the Chinese government to negotiate with Gilead as soon as possible. On the day of the interview, Redecive appeared in three treatable drugs submitted by Wuhan Virus.

On February 1, the authoritative medical journal New England Journal of Medicine (NEJM) published a number of articles about the new coronavirus (2019-nCoV) case paper, one of which is an article about the diagnosis and treatment process and clinical manifestations of the first new type of coronavirus in the United States Later, it quickly aroused domestic attention.

Screenshot from the New England Journal of Medicine website

It is worth noting that the patient’s condition improved after the injection of ridevevir and then recovered, which is undoubtedly a fact supporting the judgment that ridevevir can treat the new crown virus.

The Chinese health authorities, who are “moving in the wind,” have also quickly contacted the donor Gilead to work out whether Redecive can be safely and effectively used to treat 2019-nCoV infection.

Treatment of the first patient in the United States

According to the New England Journal of Medicine, on January 19, 2020, a 35-year-old man appeared in an emergency clinic in Snohomish County, Washington, USA. At this point, he has coughedCough and fever for 4 days. On the 15th, he returned to Washington State after visiting his family from Wuhan, China.

The patient received the news about the epidemic situation in Wuhan, China from the (CDC) from the Centers for Disease Control and Prevention, and combined his symptoms and travel history Decided to go to a doctor. The paper states that the patient reported that he had not traveled to the South China Seafood Market and had not contacted known patients.

On the 20th, the patient was diagnosed with the new coronavirus and was admitted to an isolation ward at a hospital near Seattle for treatment. The paper mentioned that the patient had nausea and vomiting when he was hospitalized, but there was no shortness of breath or chest pain, and the main physiological indicators were within the normal range. On the second afternoon, the patient developed abdominal discomfort and diarrhea at night.

The doctor then collected stool samples from patients, as well as respiratory tract samples and serum for examination. As a result, stool and respiratory tract samples were positive for 2019-nCoV, while the serum was still negative. On the third day, the patient’s X-ray chest radiograph still looked normal.

The turning point happened on the 25th. On this day, the patient had features of pneumonia in the lower lobe of the left lung. By that night, the patient’s breathing also began to change, and oxygen saturation dropped to 90%. The next day, the doctors decided to give him oxygen. At this time, the patient’s X-ray chest radiograph showed the characteristics of atypical pneumonia, and samples of multiple sites showed positive results of the new coronavirus.

In view of the continuous development of the patient’s symptoms, the doctors of the hospital after careful consideration decided to allow the patient to receive antiviral treatment on the seventh day of hospitalization-injecting the patient with ribecvir.

A turnaround followed. On the eighth day, the patient’s clinical symptoms improved immediately. He no longer needed oxygen, and his oxygen saturation returned to 94% -96%. Apart from dry cough and runny nose, he has no other symptoms. On January 30, the patient had a fever, although he was still in hospital. The only symptom is a cough, which decreases in severity.

Gilead is working closely with the Chinese health authorities

Reedivir seems to show its effect. During the treatment period of this patient, many experts have mentioned the drug among the drugs that can treat the new coronavirus. On the same day this paper was published, Gilead released the company’s chief medical officer, Merdad Par.Dr. Sey’s statement on the 2019 new coronavirus (2019-nCoV) on ongoing drug development actions.

Dr. Merdad Parsey pointed out that Gilead is currently working closely with Chinese health authorities and hopes to start a randomized, controlled clinical study as soon as possible to determine whether Redecive can be safely and effectively used to treat 2019-nCoV infection. We are also accelerating laboratory testing of Radixivir anti-2019-nCoV activity.

But he also said that Redecive has not yet been approved in any country or region in the world, and the safety or effectiveness of clinical use has not been proven. However, in order to respond to the needs of clinicians and to support the work of some drug regulatory agencies, we have carefully evaluated the risks and benefits of the drug under study that has not obtained any data in 2019-nCoV. Gilead has provided Redecive for a small number of patients who need emergency treatment but lack treatment.

At present, there are a lot of heated discussions about whether Radixivir really played a role in this case. However, the authors of the paper believe that this is a treatment based on the patient’s worsening condition, using the US “sympathetic medication” principle. Although this patient’s condition has shown rapid remission after treatment, randomized controlled clinical trials are still needed to determine the safety and effectiveness of redecive and other drugs under investigation in the treatment of new coronavirus infections .

On the 29th, Liu Wenshe, who had an exclusive interview with Yiou Health, also introduced the results of his experimental analysis and his judgment on the safety and effectiveness of treatable drugs.

The following is an excerpt from “Chinese scientists call across the oceans and negotiate as soon as possible Record of Dialogue of Xiwei for New Crown Virus :

Q1: What was your research method at that time? How to screen for available drugs?

We did analysis and comparison of RNA and protein sequences.

First, the new coronavirus is most homologous to SARS virus. Then, we selected four proteins: Spike (spike protein), RdRp (RNA replicase), 3CLpro, and PLpro.To analyze their similarity in the two viruses and their effect on the active center, make a deeper comparison.

It turns out that the spike proteins of the two viruses have no homology, especially the binding point, so the way to find spike protein blockers is not the same. But fortunately, we also found that the RNA replicase and the two major proteases 3CLpro and PLpro not only have high sequence similarity, but also highly similar simulated structural similarity, providing potential for biological agents and cyclic peptide drugs. Target. The high sequence and structure identity also indicates that small-molecule drugs targeting these enzymes can be used in the treatment of new coronaviruses without any concerns.

In addition, in terms of peptide drugs, our laboratory has a relatively special set of platforms that can specifically develop these peptide drugs. Many research groups including us have developed methods for constructing macrocyclic peptide libraries and applied them to rapid screening methods for drug targets.

Q2: What does the mutation of the spike protein on the novel coronavirus mean?

During the investigation, we compared the new coronavirus with SARS virus. As for the spike protein, when the comparison results came out, we were very shocked. Because the spike protein on the novel coronavirus has a large number of non-conservative mutations inherent in the part that binds to human receptors. This means that the existing drugs against SARS can basically be judged to be useless for new coronaviruses.

In fact, before our research results came out, there were several articles in China that showed that the relevant personnel made a simple comparison in the laboratory, but they did not notice any important amino acid mutations. Therefore, I am skeptical about the current prediction that the interaction between the receptor-binding region of the new coronavirus and the ACE2 receptor will be weaker than the SARS coronavirus.

On the contrary, I think the interaction may be stronger than SARS virus. This is also the reason why the new coronavirus is found to be more aggressive than SARS through confirmed data.

Q3: In the list published in China, Lendesivir is one of 30 kinds, but the principle of action is anti-HIV. Is it a drug for coronavirus?

Gilead developed this drug primarily to treat Ebola virus. But it was later discovered that the drug was not as effective as antibodies against Ebola virus. But MERS (Middle East Respiratory Syndrome) However, rendesivir has shown its effect. Because MERS, SARS and the new coronavirus are homologous, they are also coronaviruses and are considered Lendesivir with broad-spectrum anti-coronal activity can also be used for new coronavirus treatment.

Q4: Many of the 30 drugs are anti-HIV. How effective is it in dealing with the Wuhan epidemic?

Different genus and different genera of HIV and new coronavirus. The former belongs to the genus Lentivirus, while the latter belongs to the coronavirus genus, with different replication mechanisms and synthetases. Some anti-HIV drugs are now used because they have been approved and their pharmacology and toxicology are known.

And there are broad-spectrum protease inhibitors in anti-HIV drugs, which may have a certain inhibitory effect on the virus in Wuhan, but the effect is not so strong.

Q5: Based on your judgment that rendesivir is the only effective and safe drug at present?

First, Lendesivir has an inhibitory effect on RNA replicase and performs very well. And other major proteases, because research is not enough, there is no particularly good small molecule drugs can inhibit.

Second, Lendesivir has undergone Phase I and II clinical trials, among which there are trials on toxicology. Currently, the drug has been used in patients infected with the MERS virus. Looking at it now, it does not cause much harm to the human body.

But it is irresponsible to say that there are no side effects. Because the drug is a small molecule that inhibits RNA synthesis, it definitely has an impact on the human body, depending on the pharmacological and toxicological evaluation.

In previous media reports, Xu Shuchang also pointed out that in mice experiments, when mice were infected with the Middle East Respiratory Syndrome Coronavirus, treatment with the drug could cause the amount of virus to drop rapidly, which was more effective than protease inhibitors and interference. Good. However, it may cause pancreatitis in a small number of people, but it is relatively safe overall.

Q6: If the negotiation is successful, can the drug be used directly on patients?

It ca n’t be said that it can be used completely, because this is just a suggestion, it must be done step by step.

It can be used on some severely ill patients, that is, they will die without this medicine, and then slowly see how it works, and finally gradually spread to all patientsBy.

In addition, this requires the hospital and the patient to sign a consent agreement, while mild patients cannot use unapproved drugs.

I think that in the face of a brand new virus and a new virus treatment, what exactly the medical norms should be should be considered. This situation is a huge challenge for both the China Drug Administration and the US Drug Administration. In the face of a large number of human infections and deaths, and without any treatment, can we break some regulations and directly give drugs to patients?

Q7: Will the new coronavirus mutate and will Lendesivir continue to be effective?

The new coronavirus referred to by the Wuhan epidemic is RNA virus. One characteristic of this type of virus is that it mutates very quickly, so after the drug is applied to a patient, the virus will mutate and try to escape the process of small molecule suppression.

But it’s hard to say if there will be further mutation now. Because according to our analysis and comparison, the similarity between SARS virus and new coronavirus is relatively low, only 82% similarity in the genome. But in RNA replicase, the similarity is as high as 96%.

We can consider that the RNA replication enzyme of the new coronavirus is relatively very conservative. In other words, any mutation on this enzyme will cause the virus to fail, so the mutation speed of this enzyme will be relatively slower than that of other places, so using small molecules such as rendesivir to target the enzyme is more Safe and effective.

This article comes from Eurnet (ID: i-yiou) , the original title” The first rehabilitation of patients with new crown pneumonia in the United States, an exclusive interview with a Chinese scientist who hailed “special effects” across oceans “, author: Yi Lin age