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Dysregulation of host cell calcium signaling during viral infections: Emerging paradigm with high clinical relevance.

ABSTRACT: Viral infections are one of the leading causes of human illness. Viruses take over host cell signaling cascades for their replication and infection. Calcium (Ca²⁺) is a versatile and ubiquitous second messenger that modulates plethora of cellular functions. In last two decades, a critical role of host cell Ca²⁺ signaling in modulating viral infections has emerged. Furthermore, recent literature clearly implicates a vital role for the organellar Ca²⁺ dynamics (influx and efflux across organelles) in regulating virus entry, replication and severity of the infection. Therefore, it is not surprising that a number of viral infections including current SARS-CoV-2 driven COVID-19 pandemic are associated with dysregulated Ca²⁺ homeostasis. The focus of this review is to first discuss the role of host cell Ca²⁺ signaling in viral entry, replication and egress. We further deliberate on emerging literature demonstrating hijacking of the host cell Ca²⁺ dynamics by viruses. In particular, a variety of viruses including SARS-CoV-2 modulate lysosomal and cytosolic Ca²⁺ signaling for host cell entry and replication. Moreover, we delve into the recent studies, which have demonstrated the potential of several FDA-approved drugs targeting Ca²⁺ handling machinery in inhibiting viral infections. Importantly, we discuss the prospective of targeting intracellular Ca²⁺ signaling for better management and treatment of viral pathogenesis including COVID-19. Finally, we highlight the key outstanding questions in the field that demand critical and timely attention.

SUBMITTER: Saurav S

PROVIDER: S-EPMC8299155 | biostudies-literature |

REPOSITORIES: biostudies-literature

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