The Role of Folic Acid in SARS-CoV-2 Infection: an Intriguing Linkage under Investigation

Background: SARS-CoV-2 is a life-threatening RNA virus that may cause an acute respiratory syndrome associated with extremely high morbidity and mortality rates. Folic acid (FA), also known as folate, is an essential vitamin vital for human homeostasis, participating in many biochemical pathways, and its deficiency has been associated with viral infection vulnerability. In this review, we investigated the association between FA intake and SARS-CoV-2 infection, along with the existence of any potential impact of FA on the health outcome of patients suffering from this new viral infection. Methods: Studies included were patients' and in silico and molecular docking studies. Results: Data from in silico studies and molecular docking support that FA inhibits SARS-CoV-2 entry into the host and viral replication, binding at essential residues. Accordingly, in patients' studies, a protective role of FA supplementation against SARS-CoV-2 infection is indicated. However, contradictory data from observational studies indicate that FA supplementation, often linked to deficits during systemic inflammation due to SARS-CoV-2, increases the risk of post-infection mortality. Conclusions: Future randomized controlled trial studies, including the FA pharmacological group, are needed to better understand the role of FA as a potential protective or mortality risk indicator in COVID-19 patients.