5-amino levulinic acid inhibits SARS-CoV-2 infection in vitro

Author links open overlay panel YasuteruSakurai^ab, Mya MyatNgwe Tun^c, YoheiKurosaki^ab, TakayaSakura^d, Daniel KenInaoka^df, KiyotakaFujine^e, KiyoshiKita^fg, KouichiMorita^c, JiroYasuda^ab

Department of Emerging Infectious Diseases, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, 852-8523, Japan
National Research Center for the Control and Prevention of Infectious Diseases, Nagasaki University, Nagasaki, 852-8521, Japan
Department of Virology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, 852-8523, Japan
Department of Molecular Infection Dynamics, Shionogi Global Infectious Diseases Division, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, 852-8523, Japan
Pharmaceutical Research Department, Global Pharmaceutical R&D Division, Neopharma Japan Co., Ltd, Tokyo, 102-0071, Japan
School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, 852-8523, Japan
Department of Host – Defense Biochemistry, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, 852-8523, Japan

Highlights

5-amino levulinic acid (5-ALA) inhibited SARS-CoV-2 infection in cell culture.
Antiviral activity of 5-ALA was more potent in human colon-derived Caco-2 cells than VeroE6 cells.
The antiviral activity of 5-ALA was dose-dependent without significant cytotoxicity.

Abstract

The current COVID-19 pandemic requires urgent development of effective therapeutics. 5-amino levulinic acid (5-ALA) is a naturally synthesized amino acid and has been used for multiple purposes including as an anticancer therapy and as a dietary supplement due to its high bioavailability. In this study, we demonstrated that 5-ALA treatment potently inhibited infection of SARS-CoV-2, a causative agent of COVID-19, in cell culture. The antiviral effects could be detected in both human and non-human cells, without significant cytotoxicity. Therefore, 5-ALA is worth to be further investigated as an antiviral drug candidate for COVID-19.

Graphical Abstract:

Fig. 2

5-ALA inhibits SARS-CoV-2 infection in both VeroE6 cells and Caco-2 cells. (A) A chemical structure of 5-ALA. (B and C) To address the effects of compounds on virus infection, VeroE6 cells were treated with 1000 μM of 5-ALA with and without 25 μM of SFC for 72 h (B) or 48 h (C) and challenged with SARS-CoV-2. Virus infectivity was calculated by counting the number of infected cells and normalizing it to untreated cells (mean ± SD, n = 3). (D and E) Infectivity of SARS-CoV-2 in Caco-2 cells with pretreatment for 72 h (D) or 48 h (E) were determined as (B) and (C). Each data set is representative of at least two independent experiments.