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Anti-monkeypox Drug Discovery Against Different Drug Targets
Monkeypox is a systemic disease characterized by prodromal flu-like symptoms, progressive maculopapular rash, vesicles, and pustules. The monkeypox virus (MPXV) belongs to the Poxviridae family, the Orthopoxvirus genus, along with other animal poxviruses. The life cycle of MPXV is relatively complex. After entering the cell, about 200kb of the genome is translated in the time dimension and undergoes early, intermediate and late gene expression processes. In response to the current monkeypox outbreak, as a company leading biotechnology, Creative Biolabs provides one-stop anti-monkeypox drug discovery solutions, including drug screening and synthesis, in vitro drug testing, pharmacokinetic assays, cytotoxicity testing, drug target identification or supply of animal models.
Infection Process of MPXV
Members of orthopox viruses are similar in life cycles, nucleotide and protein homology, and even shared some degree of immune cross-protection. Poxviruses produce two distinct virion forms, mature virus (MV) and extracellular virus (EV), characterized by the amount of membrane that wraps around the central DNA core. MV consists of a viral core and a single viral membrane. The surface of the viral membrane has all the necessary proteins required for virus binding and entry into cells, so that MVs can be directly fused with the cell membrane or be endocytosed into cells through macropinocytosis. After entering cells, MPXV undergoes uncoating and early protein expression, releasing viral growth factors, interferon and other factors, protease and polymerase necessary for transcription.
After viral DNA-dependent DNA polymerase replication of MPXV genome, synthesis of intermediate and late gene products begins. Assembly of the new virus takes place in the virus factory, a process that is completed approximately four hours after infection and coincides with the late protein production process. After the assembly of the new virus, the MV virus will directly lyse the cell for release. In addition, a part of the virus will undergo membrane wrapping (EV) in the Golgi apparatus and leave the infected cell through exocytosis. EV virions account for only 1-10% of the total virus population, but are essential for cell-to-cell and long-range viral transmission and are also critical in the pathogenesis of monkeypox.
Fig 1. Observation of EV generation and drug inhibition effect via actin staining. (Priyamvada, 2020)
Cheif Services of Anti-monkeypox Drug Discovery Against Different Drug Targets
At present, there are still no approved anti-monkeypox drugs. With the continuous development of the epidemic and the in-depth research on the molecular mechanism of monkeypox virus infection in cells, drugs targeting key events and molecular products in the virus infection process are also being developed. Creative Biolabs currently provides corresponding drug discovery services for a wide range of drug targets, including:
Thanks to our professional R&D team, Creative Biolabs will carefully evaluate and plan each stage of your project. If you are looking forward to taking your drug discovery program a step further, we can always be your most reliable partner. Please feel free to contact us with our specialist for further information.
Priyamvada, L.; et al. Discovery of Retro-1 analogs exhibiting enhanced anti-vaccinia virus activity. Frontiers in Microbiology. 2020, 11: 603.