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New ideas and innovations in drug discovery

Synonymous Mutations Can Affect Protein Folding And Impair Cellular Fitness

   by Ellen Burns    58
Synonymous Mutations Can Affect Protein Folding And Impair Cellular Fitness

Synonymous codon substitutions affect the mRNA coding sequence, but the encoded amino acid sequence remains unchanged. Therefore, ostensibly these substitutions do not affect the phenotype and are often ignored in the study of human genetic variation. However, a variety of studies have shown that protein levels, translational accuracy, secretory efficiency, final folding structure and post-translational modifications are regulated by multiple mechanisms.

Synonymous codon action has gradually emerged, and the precise mechanism has yet to be discovered. Studies on the interference of synonymous codon substitution on the co-translational folding mechanism often lack in vivo evidence, and usually, rare synonymous codons tend to translate more slowly than ordinary synonymous codons. In addition, rare synonymous codons tend to appear in clusters, many of which are preserved during evolutionary history. The folding rates of many protein secondary and tertiary structures are similar to their synthesis rates, and subtle changes in elongation may also alter the folding mechanism.

Theoretically, synonymous rare codon substitutions reduce translational elongation and can provide more time for the N-terminal portion of the nascent protein to form a stable tertiary structure before the C-terminal portion emerges from the ribosome exit tunnel. Is the extra time good or bad for efficient folding? Cells contain a chaperone network to facilitate protein folding. It is unclear whether altered elongation and co-translational folding mechanisms of synonymous codons interfere with chaperone function.

New Study Shows Remdesivir Prevents Coronavirus MERS-CoV Infection In Monkeys

   by Caroline Green    233
New Study Shows Remdesivir Prevents Coronavirus MERS-CoV Infection In Monkeys

In a new study, researchers from the National Institutes of Health reported that the experimental antiviral drug remdesivir (also known as GS-5734) successfully prevented rhesus monkeys infected with the Middle East Respiratory Syndrome (MERS) coronavirus (MERS-CoV) from becoming ill from this virus infection. Giving remdesivir before infection can prevent them from getting sick, while giving this drug after they are infected can improve their condition. The results were published online February 13, 2020 in the journal PNAS, entitled "Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection".

Structural Basis of Poxvirus Transcription Revealed

   by Joanna Bowie    162
Structural Basis of Poxvirus Transcription Revealed

In order for viruses to proliferate, they usually need to be supported by infected cells. In many cases, the molecules they need to replicate their own genetic material are only found in the nucleus of the host cell before infecting other cells in the vicinity. But not all viruses enter the nucleus. Some viruses stay in the cytoplasm and must therefore be able to replicate their genetic material independently. To do so, they must bring their own "machined parts". A key player in this process is a specialized enzyme, RNA polymerase, composed of various subunits. This enzyme reads genetic information from the viral genome and transcribes it into messenger RNA (mRNA) and uses mRNA as a blueprint for proteins encoded in the genome.

The Key Role Of Stem Cells In Lethal Gastric Cancer Revealed

   by Caroline Green    183
The Key Role Of Stem Cells In Lethal Gastric Cancer Revealed

In a recent study published in Nature Communications, scientists from Cornell University made new findings in common and fatal gastric cancer research. In the United States, the incidence of gastroesophageal cancer increased 2.5-fold from the 1970s to the early 2000s, however, from the 1950s, the number of all patients with gastric cancer decreased by more than 80%; despite this, gastric cancer is still the fifth most common cancer and the third leading cause of cancer death worldwide.