Chapter 76 Dawn



"In agriculture, papers are merely a summary of your work. The essence of evaluating the quality of your work lies in the positive impact your research results have on agriculture. Publishing papers is just a secondary effect."

"I can't convince you to believe my method right now. The cabbage takes about forty days to mature. If you take good care of the crop, the final result will prove me right."

Dong Wenxu didn't know where Jiang Yan's confidence came from; he only hoped that his work during this period hadn't been in vain.

However, Dong Wenxu can find enjoyment in the planting process, and sometimes he thinks that the Chinese people have a very strong gene for farming.

Farming is an instinct deeply rooted in the genes of Chinese people, and Jiang Yan continued to devote himself to agricultural research after obtaining the standard magic brain.

If Jiang Yan can sense life, then Simmons also possesses the same ability; the characteristics bestowed by the standard demonic brain are consistent.

Simmons joined Pfizer's special drug development team, with America hoping he could work his magic.

Researchers identified twelve proteins as potential targets.

They can be broadly divided into two categories: the first is structural proteins, including spike proteins, envelope proteins, membrane proteins, nucleocapsid proteins, and another category of proteins called non-structural proteins.

The non-structural proteins mainly include proteases (M pro), papain, nsp13: helicase, nsp12: RNA-dependent RNA polymerase, nsp14: N-terminal exoribonuclease and C-terminal guanine-N7 methyltransferase, nsp15: uridine monophosphate-specific endonuclease, nsp16: 2'-O-methyltransferase, and nsp10.

The virus is responsible for replicating and packaging its nuclear material into the capsid protein shell.

Blocking any of these proteins will cause the virus to stop replicating or to stop packaging its RNA into a protein coat.

Of the 12 proteins identified as targets for controlling CoV, 3CL pro was identified as one of the most important targets due to its crucial role in mediating viral replication and transcription.

3CL pro is a chymotrypsin-like cysteine ​​protease (~33 kDa), and is similarly referred to as the major protease due to its dominant role in processing replicase polyproteins and genes.

Although 3CL pro is a dimer that provides a substrate-binding cleft, the protease exerts its proteolytic activity through a nucleophilic attack guided by cysteine ​​thiol in its Cys-His bimolecule.

There is a lack of evidence regarding the viability of 3CL pro during the viral life cycle, particularly regarding its human analogues.

Therefore, Pfizer researchers only consider 3CL pro as a potential primary drug target to bind to and inhibit viral replication activity.

They need Simmons to give his opinion from his perspective.

The 3CL pro structure is highly similar to the 3CL pro of different viral mutants, and inhibitors previously designed for MERS or SARS can also effectively combat currently prevalent viruses.

Meanwhile, an inhibitor called N2, previously designed to inhibit SARS-CoV and MERS-CoV, was also included in the testing against the virus.

Some researchers have proposed targeting 3CL pro, among which available drugs such as ritonavir, emetin, hesperidin, lopinavir, and indinavir have shown the potential to inhibit 3CL pro.

Phytochemicals in green tea have also been thoroughly evaluated to identify those with the potential to inhibit 3CL pro.

In addition, phytochemicals of neem were evaluated against the target proteins of SARS-CoV-2, namely membrane protein (M) and envelope protein (E). Nimocin, 24-Methylenecycloartan-3-one, phytosterols, Beta-Amyrin, and Nimbolin A were injected into mice by Pfizer researchers.

Simmons touched each of the mice one by one. Whether it was psychological or not, he believed that touching them personally would allow for a better assessment.

"I think this is just the best-performing guinea pig here."

The researchers nearby quickly disinfected him, and another researcher asked, "This mouse was injected with a protease inhibitor."

"We developed a protease inhibitor based on five prevalent M protease variants in the SARS-CoV-2 lineage, including G15S, T21I, L89F, K90R, and L205V."

"I think we need to observe more. We've only just completed the initial injections, and it's still unknown whether the mice that are injected with protease inhibitors later will be able to maintain their best condition."

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