Microtubules are intracellular structures that function as true cellular highways for the transport of substances, vesicles, organelles and even viruses, in the case that a cell gets infected. In most viral infections, they are the transport routes to generate the viral factories, regions close to the nucleus where virus production is concentrated.
The idea is to design drugs that, by binding to microtubules, prevent viruses from using them during the infection process. In general, drugs that target microtubules are called MTAs (microtubule targeting agents). There are two types: stabilizers (MSA) and destabilizers (MDA). Both are widely available and most of these drugs are in the WHO Essential Medicines List, and hence, they are therapeutic alternatives that are affordable and available worldwide.
Researchers from CIB Margarita Salas selected 16 commercially available MTA (including 15 in clinical use) to analyse their capacity to inhibit the viral replication against 5 different virus: the human common cold coronavirus (HCoV), the pandemic SARS-CoV-2 coronavirus, the vesicular stomatitis virus, the poxvirus vaccinia and African swine fever virus.
Scientist confirmed that the MTA tested had an effect on virus replication and spreading and that this effect varies according to the virus dependency on the microtubular network. “The inhibitory effect obtained varied depending on the specific functions that viruses have developed throughout evolution to exploit cellular transport machinery”, explains Dra. Marian Oliva, researcher at CIB Margarita Salas-CSIC.
In particular, the most complex use of microtubules filaments might correspond to coronavirus (CoVs), such as the one responsible for the Covid-19 pandemic. Microtubules are necessary both for virus internalization and later at several levels of the formation of the viral replication site. In fact, S and M coronavirus proteins (located on the virus surface) interact with tubulin (protein that forms microtubules) during the infection, although their specific function is currently unknown. Various projects involving the use of the ALBA Synchrotron are under way to study deeper these aspects.
Read more on the ALBA website
Image: Image obtained at the XALOC beamline of ALBA. Drug mebendazole (MBZ) bounds to the protein that forms the microtubules: tubulin (T2RT and T1D).