Ciliary Dysfunction Secondary to COVID-19. Explanation of the Pathogenesis From Analysis of Human Interactome With Sars-Cov-2 Proteome

Abstract

Coronavirus Disease-2019 (COVID-19) is an infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is sufficient experimental evidence to confirm that SARS-CoV-2 infection produces states of ciliary and flagellar dysfunction. However, these studies are unable to explain the observed effects molecularly, because they lack a sufficient understanding of the interaction between human proteins and virus proteins. Using the physical-chemical study of the human interactome in interaction with the SARS-CoV-2 proteome, we found evidence of interactions to explain the experimental effects from a molecular perspective. We found that ten viral proteins interact with key components in the maintenance of the molecular structure of axoneme. Additionally, we evaluated the pulmonary and extrapulmonary pathogenesis of COVID-19 from the point of view of ciliary dysfunction, and warned about other possible complications such as episodes of transient infertility that, due to the limitations of our work, would need verification.

Immunolocalization studies of vimentin and ACE2 on the surface of cells exposed to SARS-CoV-2 Spike proteins

“…This is consistent with findings from other coronaviruses [53,82], for which the presence of SARS-CoV structural proteins and viral particles associated to cilia was observed by electron microscopy [53]. Interestingly, SARS-CoV-2 infection associates with deciliation of invaded cells and cilia and flagellar dysfunction, which could occur through multiple mechanisms given the numerous interactions occurring between viral and cilia proteins (reviewed in [83,84]). Indeed, a recent hypothesis envisages that many of the pathological alterations in COVID-19 could be the result of cilia dysfunction [83].…”

“…Interestingly, SARS-CoV-2 infection has been proposed to associate with deciliation of invaded cells and cilia and flagellar dysfunction, which could occur through multiple mechanisms given the numerous interactions occurring between viral and cilia proteins (reviewed in [83,84]). Indeed, a recent hypothesis envisages that many of the pathological alterations in COVID-19 could be the result of cilia dysfunction [83]. In this context, although the function of ACE2 in cilia is not known, a potential interference of SARS-CoV-2 with cilia functions through interaction with ACE2 has been speculated [52].…”

Cell surface detection of vimentin, ACE2 and SARS-CoV-2 Spike proteins reveals selective colocalization at primary cilia

“…Thus, Spike/vimentin colocalization displays improved selectivity at primary cilia. On the other hand, SARS-CoV-2 infection has been proposed to associate with deciliation of invaded cells and cilia and flagellar dysfunction (reviewed in 86 , 87 ). In addition, dedifferentiation of multiciliated cells and loss of motile cilia have been reported after SARS-CoV-2 infection in a reconstructed human bronchial epithelium model, as well as in Syrian hamsters in vivo 88 .…”

“…In addition, dedifferentiation of multiciliated cells and loss of motile cilia have been reported after SARS-CoV-2 infection in a reconstructed human bronchial epithelium model, as well as in Syrian hamsters in vivo 88 . Indeed, a recent hypothesis envisages that many of the pathological alterations in COVID-19 could be the result of cilia dysfunction 86 . In this context, although neither the function of ACE2 or vimentin in cilia is known, it would be interesting to study their potential involvement in SARS-CoV-2-induced cilia alterations.…”