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On November 4, 2021, Merck/Ridgeback announced that its small molecule drug Molnupiravir has been approved for marketing by the British Medicines and Healthcare Products Regulatory Agency (MHRA) for the treatment of severe and mild to moderate COVID-19 adult patients with a higher risk of hospitalization
.
Molnupiravir has become the world's first oral anti-coronavirus drug approved for the treatment of mild to moderate COVID-19 in adults.
Small molecule drugs have more advantages in price and production, and are more accessible and affordable
.
As the new coronavirus (SARS-CoV-2) continues to spread and mutate, in addition to promoting vaccination, it is very important to determine a new treatment plan to end the new coronavirus pandemic
.
As an oral anti-coronavirus drug, Molnupiravir has just been approved for marketing in the United Kingdom and has been submitted to the U.
S.
Food and Drug Administration (FDA) for review
.
In view of the current pandemic situation, the potential high demand and urgency for this drug, from simple raw materials to develop a short process and sustainable synthesis method to minimize the time required for manufacturing and supply, this to Important
.
Recently, researchers from Merck & Co.
, Inc.
published a research paper titled Engineered Ribosyl-1-Kinase Enables Concise Synthesis of Molnupiravir, an Antiviral for COVID-19 in the journal ACS Central Science
.
The research achieved a new synthetic route for Molnupiravir through a biocatalytic cascade reaction with engineered ribosyl-1 kinase and uridine phosphorylase, these engineered enzymes and pyruvate oxidase enabled phosphate recovery strategy Working together, compared with the original synthetic route, the new synthetic route is shortened by 70%, and the total yield is increased by 7 times
.
Molnupiravir was originally developed to treat influenza.
Its mechanism of action is to make the virus make mistakes when copying its own RNA and produce mutations that inhibit replication
.
The results of the recent mid-term phase 3 clinical trial showed that Molnupiravir reduces the risk of hospitalization and death in COVID-19 patients, and it is equally effective against different new coronavirus mutant strains
.
As a small molecule drug, shortening the synthesis process and increasing the yield can further reduce its cost and help the rapid popularization of the drug
.
In this study, the research team developed a three-step method to synthesize Molnupiravir directly using ribose as a raw material.
They identified enzymes or chemical treatments to sequentially add appropriate chemical groups to ribose to generate molecules
.
For the second step of the synthesis, the team identified bacterial enzymes that weakly catalyze the desired reaction
.
Through in vitro evolution, they greatly enhanced the activity of these enzymes
.
The new synthetic route also includes a phosphate recovery strategy, which is 70% shorter than the original route, and the total yield is increased by 7 times
.
All in all, the research has developed an efficient and sustainable method for the synthesis of Molnupiravir using only simple raw materials and enzymes, thereby realizing the rapid supply of Molnupiravir on a large scale
.
Compared with the initial synthetic route, the new route is shortened by 70%, and the total yield is increased by about 7 times
.
These results not only provide new strategies for nucleoside-based synthesis, but also highlight the huge potential for rapid discovery and modification of new biocatalytic enzymes to increase production scale
.
Link to the paper: https://doi.
org/10.
1021/acscentsci.
1c00608, open for reprinting, welcome to forward to Moments and WeChat groups
.
Molnupiravir has become the world's first oral anti-coronavirus drug approved for the treatment of mild to moderate COVID-19 in adults.
Small molecule drugs have more advantages in price and production, and are more accessible and affordable
.
As the new coronavirus (SARS-CoV-2) continues to spread and mutate, in addition to promoting vaccination, it is very important to determine a new treatment plan to end the new coronavirus pandemic
.
As an oral anti-coronavirus drug, Molnupiravir has just been approved for marketing in the United Kingdom and has been submitted to the U.
S.
Food and Drug Administration (FDA) for review
.
In view of the current pandemic situation, the potential high demand and urgency for this drug, from simple raw materials to develop a short process and sustainable synthesis method to minimize the time required for manufacturing and supply, this to Important
.
Recently, researchers from Merck & Co.
, Inc.
published a research paper titled Engineered Ribosyl-1-Kinase Enables Concise Synthesis of Molnupiravir, an Antiviral for COVID-19 in the journal ACS Central Science
.
The research achieved a new synthetic route for Molnupiravir through a biocatalytic cascade reaction with engineered ribosyl-1 kinase and uridine phosphorylase, these engineered enzymes and pyruvate oxidase enabled phosphate recovery strategy Working together, compared with the original synthetic route, the new synthetic route is shortened by 70%, and the total yield is increased by 7 times
.
Molnupiravir was originally developed to treat influenza.
Its mechanism of action is to make the virus make mistakes when copying its own RNA and produce mutations that inhibit replication
.
The results of the recent mid-term phase 3 clinical trial showed that Molnupiravir reduces the risk of hospitalization and death in COVID-19 patients, and it is equally effective against different new coronavirus mutant strains
.
As a small molecule drug, shortening the synthesis process and increasing the yield can further reduce its cost and help the rapid popularization of the drug
.
In this study, the research team developed a three-step method to synthesize Molnupiravir directly using ribose as a raw material.
They identified enzymes or chemical treatments to sequentially add appropriate chemical groups to ribose to generate molecules
.
For the second step of the synthesis, the team identified bacterial enzymes that weakly catalyze the desired reaction
.
Through in vitro evolution, they greatly enhanced the activity of these enzymes
.
The new synthetic route also includes a phosphate recovery strategy, which is 70% shorter than the original route, and the total yield is increased by 7 times
.
All in all, the research has developed an efficient and sustainable method for the synthesis of Molnupiravir using only simple raw materials and enzymes, thereby realizing the rapid supply of Molnupiravir on a large scale
.
Compared with the initial synthetic route, the new route is shortened by 70%, and the total yield is increased by about 7 times
.
These results not only provide new strategies for nucleoside-based synthesis, but also highlight the huge potential for rapid discovery and modification of new biocatalytic enzymes to increase production scale
.
Link to the paper: https://doi.
org/10.
1021/acscentsci.
1c00608, open for reprinting, welcome to forward to Moments and WeChat groups