Abstract
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection and associated coronavirus disease 2019 (COVID-19) has severely impacted human well-being. Although vaccination programs have helped in reducing the severity of the disease, drug regimens for clinical management of COVID-19 are not well recognized yet. It is therefore important to identify and characterize the molecular pathways that could be therapeutically targeted to halt SARS-CoV-2 infection and COVID-19 pathogenesis. SARS-CoV-2 hijacks host cell molecular machinery for its entry, replication and egress. Interestingly, SARS-CoV-2 interacts with host cell Calcium (Ca2+) handling proteins and perturbs Ca2+ homeostasis. We here systematically review the literature that demonstrates a critical role of host cell Ca2+ dynamics in regulating SARS-CoV-2 infection and COVID-19 pathogenesis. Further, we discuss recent studies, which have reported that SARS-CoV-2 acts on several organelle-specific Ca2+ transport mechanisms. Moreover, we deliberate upon the possibility of curtailing SARS-CoV-2 infection by targeting host cell Ca2+ handling machinery. Importantly, we delve into the clinical trials that are examining the efficacy of FDA-approved small molecules acting on Ca2+ handling machinery for the management of COVID-19. Although an important role of host cell Ca2+ signaling in driving SARS-CoV-2 infection has emerged, the underlying molecular mechanisms remain poorly understood. In future, it would be important to investigate in detail the signaling cascades that connect perturbed Ca2+ dynamics to SARS-CoV-2 infection.
【저자키워드】 COVID-19, SARS-CoV-2, clinical trials, Calcium signaling, Host cell calcium dynamics, 【초록키워드】 coronavirus disease, Efficacy, vaccination, clinical trial, SARS-COV-2 infection, severity, Infection, molecular mechanism, Replication, Protein, COVID-19 pathogenesis, management, pathway, Clinical management, small molecule, mechanisms, molecular, respiratory, Critical, calcium, homeostasis, Signaling, host cell, Transport, handling, driving, identify, reported, the disease, reducing, interact, signaling cascade, acting, impacted, drug regimen, 【제목키워드】 SARS-COV-2 infection, COVID-19 pathogenesis, host cell, Potential, curtail,