Microorganisms reveal the molecular mechanism by which monkeypox virus polymerase holases work

Monkeypox is a zoonotic viral disease
caused by the monkeypox virus.
On 23 July 2022, the World Health Organization declared the monkeypox outbreak a global public health emergency
.
More than 82,000 people worldwide have been infected with monkeypox virus
.
Like poxvirus and smallpox virus, which are also genus orthopoxvirus, monkeypox virus forms a replication factory in the cytoplasm of host cells for genome replication, producing end-to-end DNA multi-tandem, which is then decomposed into a single viral genome
under the action of dissociation enzymes.
When DNA genome synthesis takes place, at least 8 viral proteins need to cooperate with each other to complete the entire process
.
Among them, the polymerase holase complex composed of polymerase F8, sustainable factor E4 and A22 heterodimer is the core component of the viral replication machine and is directly responsible for synthesizing daughter DNA.
It is an ideal target
for antiviral drug development.
Previous studies on the replication mechanism of pox-seedling virus have given us a preliminary understanding of the genome replication process of orthopoxvirus, but the high-resolution structure of orthopoxvirus polymerase holase complex and the molecular mechanism of sustainable genome synthesis still need to be thoroughly studied
.

The research team analyzed the high-resolution three-dimensional structure of polymerase holase in replication conformation, and revealed the molecular mechanism of polymerase generation of offspring.
At the same time, it was clarified that monkeypox virus polymerase is through a "forward sliding clamp" Special models to increase sustainable synthetic capacity (Figure 1).

In addition, it was also found that the binding pattern of monkeypox virus polymerase to nucleic acids was very similar to that of other B group DNA polymerases, indicating that it had a certain degree of conservation in evolution, which provided a structural basis and theoretical basis
for the further development of drugs against monkeypox virus.