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Anti-flu drug battle: Why is Omanta sure that he can't fight the mutated M2?
Mutation of influenza viruses, especially the M2 protein in influenza A, has become an important challenge in the development of anti-influenza drugs.M2 protein plays a key role in influenza viruses, and its unique proton conduction properties make it a major target for drug attacks.However, as the virus mutates rapidly, the traditional anti-flu drug, Omantadine, appears powerless.
Structure and Functions of M2
M2 protein is a proton-selective viroporin in the influenza A virus capsule, usually in the form of a tetramer, forming a proton channel.The opening of this channel will be affected by the low pH environment and will be extremely sensitive to the conduction of protons.
The core structure of the M2 protein consists of 97 amino acids and includes an extracellular N-terminal domain, a transmembrane segment, and an intracellular C-terminal domain.
In these three regions, His37 and Trp41 are considered important amino acid residues, responsible for pH sensing and switching of channels, respectively.These characteristics allow M2 to regulate internal pH during viral replication to promote the fusion of the virus and host cells.
Evolution of drug resistance of M2 protein
Omantadine has a long history of use, but its effect has dropped significantly when facing the mutated M2 protein.After the flu virus continues to mutate, many cells develop resistance to wavy drugs.In particular, the emergence of the S31N mutation hindered the effect of Omantading.
According to the CDC, most of the prevalent influenza A viruses have become resistant to omantading and its derivatives over time.
BM2 and CM2: The response mechanism of other influenza viruses
In addition to influenza A virus, the M2 proteins of influenza B and influenza C viruses also shoulder similar functions.However, they have little similarity in sequence to M2 proteins of type A.
BM2 protein is not affected by Omantading and limanatidine, which allows the B virus to maintain its infectious capacity when facing the same drug.
Study shows that the channel function of type B M2 is significantly higher than that of type A M2, but the conductivity pH characteristics of the two are similar.
Future Challenges
As the flu virus continues to evolve, existing anti-influenza drugs face unprecedented challenges.The development of new antiviral drugs will be an important direction for future public health research.In-depth research on M2, especially effective drugs that identify and target M2 variants, will become the focus of the scientific community.
In the current epidemic situation, we should probably think: How to find new strategies to fight influenza in the changing viral environment?
