Potential of targeting host cell calcium dynamics to curtail SARS-CoV-2 infection and COVID-19 pathogenesis

• Published in: Cell calcium (Edinburgh) 2022-09, Vol.106, p.102637-102637, Article 102637
• Main Authors: Sultan, Farina, Ahuja, Kriti, Motiani, Rajender K.
• Format: Article
• Language: English
• Subjects: Calcium - metabolism; Calcium signaling; Clinical trials; COVID-19; Host cell calcium dynamics; Humans; Review; SARS-CoV-2
• ISSN: 0143-4160; 1532-1991
• DOI: 10.1016/j.ceca.2022.102637

•SARS-CoV-2 hijacks host cell Ca2+ dynamics for its benefit.•Several SARS-CoV-2 proteins interact with host cell Ca2+ handling machinery.•SARS-CoV-2 acts on organelle-specific Ca2+ transport mechanisms.•Literature suggests that host cell Ca2+ dynamics can be potentially targeted for clinical management of COVID-19.•Multiple clinical trials are investigating the efficacy of FDA-approved small molecules that act on Ca2+ handling machinery for treatment and/or management of COVID-19. 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.