Any specific microtubule inhibitors that can be designed against specific viruses to block their entry and aggregation into host cells?
1. Reovirus Cell Entry Requires Functional Microtubules
http://mbio.asm.org/content/4/4/e00405-13
2. Microtubules in viral replication and transport.
Niehl A1, Peña EJ, Amari K, Heinlein M.
http://www.ncbi.nlm.nih.gov/pubmed/23379770
I believe they have different roles in different viral infections...
In pseudorabies for example they seem to help the virus shed antigens that helps it mask itself against the immune response:
http://www.ncbi.nlm.nih.gov/pubmed/?term=Involvement+of+Cellular+Cytoskeleton+Components+in+Antibody-Induced+Internalization+of+Viral+Glycoproteins+in+Pseudorabies+Virus-Infected+Monocytes
That paper also mentions some inhibitors for blocking of microtubule polymerization, but I'm not sure how specific you need them to be.
Best regards and good luck.
As conduits for intracellular transport, many viruses take advantage of this "rail system" through interactions with dynamin and other molecular transport proteins. In herpesvirus infection, capsids are actively transported to the MOC and then to the nuclear pore via microtubules. There are numerous other examples, as well, so, the "exact answer" is specific to each evolved virus-cell interaction.
There is not one role, as Kalina and Mark said. And since blocking microtubule polymerization could cause pathology itself, I tend to doubt that an anti-viral based on that would be practical. Could be an interesting research question though, that could lead into embryo development, memory, and other directions.
I agree with Brian. Microtubules are crucial for normal cell function and blocking their polymerization will not only inhibit a virus replication but also decrease cell viability. That is not a good anti-viral strategy.
Thanks to everyone for all your valued comments.
As Prof. Brian and Dr. Anna have mentioned above, it might not be a good strategy to attack polymerizing microtubules (although some agents disrupt microtubules, i.e., in chemotherapy there are some mitotic inhibitors which interfere with microtubules) since they involve normal cell differentiation and function. I was just exploring whether it could be a feasible strategy since some viruses employ host microtubules to gain entry into host cells or move out of the nucleus (analogously referring to Dr. Mark's capsid transport above).
As Dr. Kalina has pointed out to a reference which is interesting, and pointing to the fact that viruses employ host cellular cytoskeletal structures during physiological endocytosis and internalization of viral glycoproteins, the use of some chemotherapeutic agents resulted in significant reduction in such internalization process. How far this could be applicable, or relevant to other viruses?
Referring to Dr. Anna's paper,
HSV-1 Glycoproteins Are Delivered to Virus Assembly Sites Through Dynamin-Dependent Endocytosis
https://www.researchgate.net/publication/282874995_HSV-1_Glycoproteins_Are_Delivered_to_Virus_Assembly_Sites_Through_Dynamin-Dependent_Endocytosis
This sounds interesting, referring to the paper above by Dr. Anna et al:
"Moreover inhibitors targeting dynamin and clathrin lead to a decreased transport of glycoproteins to cytoplasmic capsids confirming that glycoproteins are delivered to assembly sites via endocytosis."
The paper above as well, highlights the importance of dynamin-dependent endocytosis in viral assembly. However, this is prior to endocytosis when compared to Van de Walle (2001) physiological endocytosis during internalization. I assume that if this step before internalization (and endocytosis) is targeted, we may have a say to block viral assembly.
Best Regards, Sidharta
Article HSV-1 Glycoproteins Are Delivered to Virus Assembly Sites Th...
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