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Clinical human trials begin for COVID-19 vaccine in China

Zhong Nanshan, Chen Wei embark on new type of vaccine R&D
By Zhao Yusha and Huang Lanlan
Published: Mar 06, 2021 08:23 PM

Sinovac FINAL

File photo​

Thanks to a nano-carrier research breakthrough, Chinese scientists, including top epidemiologist Zhong Nanshan, have embarked on developing an advanced type of COVID-19 mRNA vaccine, which can be preserved for half a year under the condition of two to eight degrees Celsius.

Under the organization of China's top respiratory disease expert Zhong Nanshan, Zhang Biliang, founder of Guangzhou RioBio Co. biotechnology company has recently briefed China’s vaccine developers on the new progress of COVID-19 vaccines, the Science and Technology Daily reported on Saturday.

Zhang said that the mRNA COVID-19 vaccine developed by his team can be preserved for half a year under the condition of two to eight degrees Celsius; whilst the mRNA vaccines made by other companies, have to be stored at minus 70 degrees Celsius, like the Pfizer vaccine. Some need to be stored at minus 20 degrees Celsius.

Zhong’s team has already embarked on researching this project, which has also been listed by the Ministry of Science and Technology as a key R&D project on coronavirus.

Zhang has compared mRNA vaccines to an egg, the shell that encompass the egg in fact is a lipid compound. Different vaccine producers such as Pfizer and Moderna are searching for different formulas to make the “shell” safer and more stable, said Zhang.

The mRNA COVID-19 vaccine injected in other countries is designed to use a nano artificial “shell” (Liposomal nanoparticles), and use it to bring mRNA into cells to instruct them to make antigens and stimulate the immune system to make antibodies against coronavirus.

Zhang said that based on their previous experience on medicine R&D, the team has managed to develop special lipid nanoparticles, that enable the vaccine to be preserved in higher temperatures for longer time.

The safety standards for the vaccine carrier are extremely high, which requires it to send the mRNA in a short time and make it disappear after completing its task, according to Zhang.

He said his team has finished clinical research testing on animals, and is steadily pushing forward the process.

He also said that his company has the biggest mRNA raw material factory, which allows rapid mass production of such a vaccine.

The development of COVID-19 mRNA vaccines in China, although starting later than some Western countries, focuses more on improving storage limits of the vaccines as it is directly aimed at future mass vaccination among people, said Tao Lina, a Shanghai-based vaccine expert.

The capacity to produce COVID-19 mRNA vaccines is not a problem for China, Tao told the Global Times on Saturday, saying there have been several domestic institutes and companies developing this vaccine.

China’s first mRNA COVID-19 vaccine production plant, for instance, is under construction in Yuxi, Southwest China’s Yunnan Province, Tao said. “The plant is expected to produce 120 million doses of vaccines annually,” he added.

Research on a new type of nano-carrier vaccine has also witnessed a breakthrough on cooperation between Chen Wei, a researcher at the Institute of Military Medicine under the academy of Military Sciences and the National Center for Nanoscience and Technology.

The nano-carrier system is like a vehicle with a navigation system, which helps to transport the medicine to certain locations, said Zhao Yuliang, chief of the center, noting that on one hand it elevates efficiency of the medicine, and on the other, reduces side effects.

Chen, who also leads a team developing CanSino's recombinant COVID-19 vaccine, used recombinant adenovirus vector technology, which is similar to the Ebola vaccine approach. “Virus vector and nano-carriers share similarities,” said Zhao, noting his center and Chen’s team chimed in easily based on their experiences.

Zhao noted that COVID-19 has broken the boundaries of different walks of science. “China leads the world in basic scientific research on nano-particles. But nano-researchers have little contact with vaccine producers. It is COVID-19 that has broken such boundary,” he said.
 
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Hilda Bastian, PhD @hildabast

The UAE has begun injecting a 3rd dose of Sinopharm's inactivated Beijing vaccine for people who had low antibody levels are the ordinary course (3rd dose = 2nd boost). Number said to be "minimal". https://thenationalnews.com/uae/health/first-booster-shots-of-covid-19-vaccine-administered-in-uae-1.1180482… Which I guess means that everyone's been getting tested.
Hilda Bastian, PhD @hildabast

A phase 4 trial in China for vaccinating with Covid vaccine (appears to be Sinopharm's Beijing vaccine, calling it COVIV) & flu or pneumococcal vaccine: https://clinicaltrials.gov/ct2/show/NCT04790851… Safety & immunogenicity outcomes, in China: 1,152 people
 
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Few virus infections reported among vaccinated people in Turkey
A man gets vaccinated against the coronavirus, in Antalya, southern Turkey, March 5, 2021. (İHA PHOTO)
A man gets vaccinated against the coronavirus, in Antalya, southern Turkey, March 5, 2021. (İHA PHOTO)

BY DAILY SABAH
MAR 12, 2021 1:53 PM

An official from Turkey’s top body overseeing the fight against COVID-19 said only 852 people who received two doses of the vaccine were infected and none died, though a few were hospitalized

A vaccination drive has been underway in Turkey against the coronavirus since January. As the public wondered about whether the vaccine would help in protecting them against the deadly disease, professor Mustafa Necmi Ilhan assured them of its efficacy. Ilhan, a member of the Health Ministry’s Coronavirus Scientific Advisory Board, said Friday that only 852 of the 1.3 million people who had received both doses of the vaccine were diagnosed with the virus. Fifty-three of them were hospitalized, while five among the hospitalized were in intensive care. Three out of five have already been discharged from the hospital, he said.

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China approves fourth COVID-19 vaccine for emergency use
By Global Times
Published: Mar 15, 2021 11:15 PM

Photo: Institute of Microbiology, Chinese Academy of Sciences
Photo: Institute of Microbiology, Chinese Academy of Sciences

China has approved the fourth COVID-19 vaccine for emergency use, a Chinese hamster ovary (CHO) cell vaccine jointly developed by experts from the Chinese Centers for Disease Control and Prevention (China’s CDC) and the Chinese Academy of Sciences (CAS), the academy announced Monday.

On February 22, the Uzbek legislature approved the Emergency Use Authorization (EUA) for the vaccine in Uzbekistan. The vaccine was approved for use on March 1. Uzbekistan rates the vaccine as one of the safest and most effective in the world.

The vaccine, developed by a team led by Gao Fu, director of China’s CDC, is one of the five technical routes, laid out by the scientific research team of the State Council, for the joint prevention and control mechanism of COVID-19.

The academy’s statement said the vaccine completed phases I and II of the clinical trials in October 2020. The results showed that there were no serious adverse reactions after complete inoculation. The neutralizing antibody level produced by the vaccine was comparable to that of other recombinant protein vaccines and mRNA vaccines currently used worldwide, meeting advanced international standards.

Phase III of clinical trials of the vaccine was launched in China, Uzbekistan, Pakistan, Ecuador and Indonesia, in November 2020, with 29,000 participants scheduled to be vaccinated.

The Phase III of the clinical trial is progressing well, particularly with high recognition from Uzbekistan, the country where the trial was first started, the statement said.

The CHO cell vaccine does not require a high-level biosafety laboratory production facility. The production process is stable and reliable, and production can be quickly increased at home and abroad, significantly reducing production costs, and is convenient for storage and transportation.
 
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China approves fourth COVID-19 vaccine for emergency use
By Global Times
Published: Mar 15, 2021 11:15 PM

Photo: Institute of Microbiology, Chinese Academy of Sciences
Photo: Institute of Microbiology, Chinese Academy of Sciences

China has approved the fourth COVID-19 vaccine for emergency use, a Chinese hamster ovary (CHO) cell vaccine jointly developed by experts from the Chinese Centers for Disease Control and Prevention (China’s CDC) and the Chinese Academy of Sciences (CAS), the academy announced Monday.

On February 22, the Uzbek legislature approved the Emergency Use Authorization (EUA) for the vaccine in Uzbekistan. The vaccine was approved for use on March 1. Uzbekistan rates the vaccine as one of the safest and most effective in the world.

The vaccine, developed by a team led by Gao Fu, director of China’s CDC, is one of the five technical routes, laid out by the scientific research team of the State Council, for the joint prevention and control mechanism of COVID-19.

The academy’s statement said the vaccine completed phases I and II of the clinical trials in October 2020. The results showed that there were no serious adverse reactions after complete inoculation. The neutralizing antibody level produced by the vaccine was comparable to that of other recombinant protein vaccines and mRNA vaccines currently used worldwide, meeting advanced international standards.

Phase III of clinical trials of the vaccine was launched in China, Uzbekistan, Pakistan, Ecuador and Indonesia, in November 2020, with 29,000 participants scheduled to be vaccinated.

The Phase III of the clinical trial is progressing well, particularly with high recognition from Uzbekistan, the country where the trial was first started, the statement said.

The CHO cell vaccine does not require a high-level biosafety laboratory production facility. The production process is stable and reliable, and production can be quickly increased at home and abroad, significantly reducing production costs, and is convenient for storage and transportation.
This is a very clever shit. Media usually mentions about 4 technical routes for covid vaccines. This one is none of them and really unique.
 
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Please Note this is drug, not vaccine.

0619Cover.jpg
Structure-based Design of Antiviral Drug Candidates Targets SARS-CoV-2 Main Protease
Editor: LIU Jia | Apr 22, 2020

A team of Chinese scientists has recently developed two novel compounds that inhibit the SARS-CoV-2 main protease (Mpro) and one of them is a good drug candidate for further clinical studies.

The research, published online in Science on April 22, was conducted by Prof. LIU Hong and Prof. XU Yechun from the Shanghai Institute of Materia Medica (SIMM) of the Chinese Academy of Sciences (CAS), Prof. YANG Haitao from the Shanghai Institute for Advanced Immunochemical Studies of ShanghaiTech University, Prof. ZHANG Lei-Ke from the Wuhan Institute of Virology of CAS, and their collaborators.

As of April 22, more than 2.5 million cases of COVID-19 have been confirmed, with more than 170 thousand deaths. No clinically effective vaccines or specific antiviral drugs are currently available for the prevention and treatment of COVID-19.

SARS-CoV-2 – the etiological agent responsible for the global COVID-19 outbreak – is an enveloped, positive-sense, single-stranded RNA virus and SARS-CoV-2 Mpro plays a vital role in its life cycle. Since SARS-CoV-2 Mpro has no human homologue, it is an ideal antiviral drug target.

After analyzing the substrate-binding pockets of SARS-CoV-2 Mpro, the scientists designed and synthesized two compounds, 11a and 11b. A fluorescence resonance energy transfer (FRET)-based cleavage assay was then used to determine their IC50 values. The results revealed excellent SARS-CoV-2 Mpro inhibitory activity for both 11a and 11b, with IC50 values of 0.053 ± 0.005 μM and 0.040 ± 0.002 μM, respectively.

The researchers also employed immunofluorescence, quantitative real-time PCR and plaque assay to monitor the antiviral activity of 11a and 11b. The results all showed that compounds 11a and 11b exhibited good anti-SARS-CoV-2-infection activity in cell culture (e.g., EC50 values were 0.53 ± 0.01 μM and 0.72 ± 0.09 μM, respectively, when using the plaque assay). In addition, these compounds showed good PK properties in vivo, suggesting they are promising drug candidates. However, the lower toxicity of compound 11a makes it particularly promising.

In order to elucidate the inhibition mechanism of SARS-CoV-2 Mpro in compounds 11a and 11b, the scientists determined the high-resolution crystal structure of complexes Mpro-11a (PDB: 6LZE) and Mpro-11b (PDB: 6M0K) at 1.5-A resolution. The high-resolution crystal structure of these complexes not only demonstrated SARS-CoV-2 Mpro-11a/11b interactions, but also revealed the mechanism of SARS-CoV-2 inhibition. High-resolution analysis of complexes is useful to medicinal chemists in designing novel inhibitors that act against SARS-CoV-2.

This study shows that structure-based drug design is an effective strategy for designing specific antiviral leads against SARS-CoV-2. Preclinical research on compound 11a is now proceeding. The team has decided to share its research data with scientists around the world to accelerate the development of anti-SARS-CoV-2 drugs.

In this study, the team led by Profs. LIU Hong, XU Yechun and JIANG Hualiang accomplished the design and synthesis of compounds and evaluated enzyme inhibitory activity; the team led by Profs. YANG Haitao and RAO Zihe determined the high-resolution crystal structure; and the team led by Profs. ZHANG Lei-Ke and XIAO Gengfu tested the antiviral activity. The research was also supported by the National Chengdu Center for Safety Evaluation of Drugs and Frontier Biotechnologies Inc.

W020200422548879490461.jpg
Figure: Mpro-inhibitor binding modes for 11a and 11b. (Image by SIMM)

Structure-based Design of Antiviral Drug Candidates Targets SARS-CoV-2 Main Protease----Chinese Academy of Sciences
Chinese COVID-19 drug candidate undergoes clinical trials in U.S.
Source: Xinhua| 2021-03-17 17:06:31|Editor: huaxia

139816893_16159719911371n.jpg
Photo taken on Dec. 11, 2020 shows the U.S. Food and Drug Administration in Silver Spring, Maryland, the United States. (Photo by Ting Shen/Xinhua)

SHANGHAI, March 17 (Xinhua) -- A Chinese COVID-19 drug candidate is undergoing clinical trials in the United States after receiving approval from the U.S. Food and Drug Administration (FDA), the drugmaker said on Wednesday.

Clinical research permits for the drug, coded DC402234, were sought from both China's National Medical Products Administration and the U.S. FDA in July 2020, the Shanghai Institute of Materia Medica of the Chinese Academy of Sciences (CAS), the major developer of the drug, said in a statement.

Researchers commenced phase-1 clinical trials for the drug on Monday at a clinical research center of New Jersey-based Frontage Laboratories, Inc., according to the institute.

The drug is a novel compound designed and synthesized based on the crystal structure of the coronavirus' main protease, a key enzyme that plays a pivotal role in mediating viral replication and transcription. Preclinical research showed that the compound exhibited potent inhibitory activity against the protease and good antiviral activity in cell culture.

Good pharmacokinetic properties -- how a drug is absorbed and moves through the body, and its safety in animal trials -- also suggested the potential for further clinical tests, the statement read.

The results were reported in a paper titled "Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease," published as the cover story for the journal Science in June 2020.

The patented drug was jointly developed by researchers from the ShanghaiTech University and the Wuhan Institute of Virology under the CAS.
 
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Global Times @globaltimesnews
China state-affiliated media

Tibet Rhodiola Pharmaceutical announced Tue that the #COVID19 vaccine product developed by StemiRna based on the #mRNA technology has been approved for clinical trials in China and will be carried out as planned.

Image
10:04 AM · Jan 5, 2021
Phase-1 clinical trials for Shanghai vaccine
Yang Jian
21:01 UTC+8, 2021-03-25

Phase-1 clinical trials for Shanghai vaccine
Li Lanjuan (left), a Chinese epidemiologist, and experts from Shanghai East Hospital discuss the clinical trials of a COVID-19 vaccine developed in Shanghai.

A locally developed COVID-19 vaccine has entered phase-I clinical trials in neighboring Zhejiang Province.

The mRNA (messenger ribonucleic acid) vaccine developed by Stemirna and Shanghai East Hospital will be tested on people aged 18 and above at Shulan (Hangzhou) Hospital, where similar trials have been conducted.

In cooperation with the Chinese Center for Disease Control and Prevention, the local team began its research in January last year, shortly after the coronavirus outbreak.

Based on the city’s mRNA emergency vaccine technology innovation center and the stem cell bank in Zhangjiang High-tech Park in Pudong, the team finished integration, production and testing of a vaccine sample in 40 days.

The vaccine was listed as one of the five emergency researches for COVID-19 vaccines by China’s Ministry of Science and Technology and overseen by the National Health Commission. It was approved by the National Medical Products Administration for clinical trials on January 4.

It is based on mRNA technology, which is used to deliver genetic material to the body and make human cells create a protein from the virus. This trains the immune system to be ready to attack if it encounters SARS-CoV-2.

The vaccine is one of the specialized projects of the vaccine lab at Tongji University, which has conducted multiple clinical trials for mRNA tumor vaccines.

The lab is expected to become a vaccine strategic bank of Shanghai with its rapid and highly efficient research capability during major public health incidents, said Liu Zhongmin, the hospital’s president.
 
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Inhibitors to target SARS-CoV-2 viral protein display strong antiviral activity in transgenic mouse model
Reviewed by Emily Henderson, B.Sc.
Feb 18 2021

Inhibitors based on approved drugs and designed to disrupt the SARS-CoV-2 viral protein Mpro display strong antiviral activity both in vitro and in a transgenic mouse model, a new study reports. While vaccines are an important tool in the fight against COVID-19, it remains a high priority to develop antiviral drugs, especially with the rise of variants that may partially evade vaccines.

The viral protein Mpro is a protease that is required for cleaving precursor polyproteins into functional viral proteins. This essential function makes it a key drug target. Jingxin Qiao et al. designed 32 inhibitors based on either Boceprivir or Teleprovir, both of which are protease inhibitors approved to treat hepatitis C virus.

Six compounds protected cells from viral infection with high potency and two of these were selected for in vivo studies based on pharmacokinetic experiments. In a SARS-CoV-2 infection transgenic mouse model, treatment with both compounds greatly reduced lung viral loads and lung lesions.

Both also displayed good pharmacokinetic properties and safety in rats. The work in this paper "represents an important step toward the development of orally available anti-SARS-CoV-2 drugs," the authors say.

Source:
American Association for the Advancement of Science
Journal reference:
Qiao, J., et al. (2021) SARS-CoV-2 Mpro inhibitors with antiviral activity in a transgenic mouse model. Science. doi.org/10.1126/science.abf1611.

 
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