The folic acid metabolite 7,8-dihydrofolate can decrease the interactions of ACE2 with the Wild type, but not with the Beta and Delta SARS-CoV-2 variants: A silico study.

Abstract

There is evidence that high levels of folic acid in human plasma may prevent SARS-CoV-2 infections or reduce its symptoms. However, the mechanisms that enable this inhibition are still unknown. This article proves, through molecular dynamics simulation, that folic acid metabolite 7,8-dihydrofolate (DHF) has high affinity to bind as ligands to the angiotensin-converting enzyme 2 (ACE2), and when this complex has been formed, the Wild type SARS-CoV-2 virus cannot bind to the ACE2 receptor, possibly inhibiting infection to the host cell. In contrast, the Beta and Delta variants of this same virus can join the ACE2 with high affinity even with the presence of DHF. This results lead to the conclusion that DHF may inhibit infection from the Wild type SARS-CoV-2 virus, but not its Beta and Delta variants. These results could explain the almost double increase in severe cases of COVID-19 due to the delta variant in pregnant women compared to the Wild type SARS-CoV-2.