Li Wenhui: Two major challenges in the development of macromolecule drugs for the new coronavirus

On the evening of March 16, Li Wenhui, a senior researcher at the Beijing Institute of Life Sciences, said in a scientific lecture on Understanding the Future that the research and development of new coronavirus macromolecules still faces at least two major scientific challenges, but with the deepening of research, it is still promising to develop effective drugs. The new coronavirus belongs to the RNA virus, unlike the DNA virus, RNA virus must be continuously and actively copied in the cytoplasm to be present in cells for a long time.

Li Wenhui: Two major challenges in the development of macromolecule drugs for the new coronavirus

“This means that any key enzyme or key protein in the RNA virus is missing or damaged, and the virus cannot be continuously replicated.” “

“So from a virological point of view, RNA viruses can be wiped out like hCV if they are studied deep lying enough to find the right target,” Li said. “

Coronary viruses are the largest known RNA viruses, and the largest genomes mean that there are the largest targets. But why do human coronaviruses such as SARS and MERS still lack special drugs today?

Li Explained to The China Science Daily that the main reason sits on persistent investment and has not been a major target for research and development.

“I personally believe that as humans conduct an in-depth study of the new coronavirus, it is possible to find effective targets for effective drug treatment. “

Academics are very concerned about two important enzymes of coronaviruses, one is protease and the other is RNA polymerase (RDRP).

Drugs such as Cressin, which are currently used for treatment, are protease inhibitors, while Ridsewe is an RDRP inhibitor.

The “old drug” of these small moleculeantiviral drugs is seen as the most available means of fighting new coronavirus infection.

Li Wenhui stressed the importance of macromolecule drugs.

Compared with small molecule drugs, the number of large molecular drugs given is small, high safety, high resistance barrier, not affected by the epitope of immune advantage, and is also effective for infants, the elderly and other groups with poor vaccination response.

But at the same time, macromolecule drugs also have inconvenient methods of administration, complex production process, relatively high cost and so on.

“The macromolecule drugs against neo-coronavirus can be divided into two types: antibodies and fusion proteins, which have a common mechanism of action that blocks the combination of neo-coronavirus and ACE2. “

“The antibody technology is more mature, but the disadvantage is that the virus is prone to mutation softening of antibodies, so that the antibody effect fails, and ACE2-Fc fusion protein can ‘change in constant change’, but the disadvantage is complex process,” Li said. “

Li Wenhui said that the new coronavirus macromolecule drugs face two major challenges.

The first step is to know whether the new coronavirus has cell-to-cell transmission, whether it can avoid the receptor binding into the cell.

In the case of HIV, for example, the intercellular transmission of its presence can interfere with the effectiveness of macromolecule drugs.

According to previous studies, the new coronavirus has the probability of intercellular diffusion using sugar molecules, but this probability is not very high.

Second, it is necessary to confirm whether the new coronavirus has antibody-dependent viral infection enhancement (ADE) effect. The ADE effect is prominent in dengue virus infection.

When there is an ADE effect, symptoms are more severe when a second infection, especially when it is different from the first infection, is not the same.

“We don’t know at this time whether the new coronavirus has this ADE effect. “However, studies of SARS virus and MERS virus have found that although low affinity antibodies of S proteins can mediate the virus into immune cells, the virus cannot be actively replicated and eventually only ‘abortion infections’.” “

He said that studying whether the new coronavirus has an ADE effect will provide an important basis for antibody therapy and vaccine development.