How COVID-19 Hijacks the Cytoskeleton: Therapeutic Implications.

ABSTRACT: The SARS-CoV-2 virus invades and replicates within host cells by "hijacking" biomolecular machinery, gaining control of the microtubule cytoskeleton. After attaching to membrane receptors and entering cells, the SARS-CoV-2 virus co-opts the dynamic intra-cellular cytoskeletal network of microtubules, actin, and the microtubule-organizing center, enabling three factors that lead to clinical pathology: (1) viral load due to intra-cellular trafficking, (2) cell-to-cell spread by filopodia, and (3) immune dysfunction, ranging from hyper-inflammatory cytokine storm to ineffective or absent response. These factors all depend directly on microtubules and the microtubule-organizing center, as do cell functions such as mitosis and immune cell movement. Here we consider how the SARS-CoV-2 virus may "hijack" cytoskeletal functions by docking inside the microtubule-organizing center's centriole "barrels", enabling certain interactions between the virus's positively charged spike ("S") proteins and negatively charged C-termini of the microtubules that the centriole comprises, somewhat like fingers on a keyboard. This points to the potential benefit of therapies aimed not directly at the virus but at the microtubules and microtubule-organizing center of the host cell on which the virus depends. These therapies could range from anti-microtubule drugs to low-intensity ultrasound (megahertz mechanical vibrations) externally applied to the vagus nerve at the neck and/or to the spleen (since both are involved in mediating inflammatory response). Given that ultrasound imaging machines suitable for vagal/splenic ultrasound are available for clinical trials in every hospital, we recommend an alternative therapeutic approach for COVID-19 based on addressing and normalizing the host cell microtubules and microtubule-organizing centers co-opted by the SARS-CoV-2 virus.

SUBMITTER: Aminpour M 

PROVIDER: S-EPMC9225596 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature