Open AccessCombined Metabolic Activators Accelerates Recovery in Mild‐to‐Moderate COVID‐19
Author(s) -
Altay Ozlem,
Arif Muhammad,
Li Xiangyu,
Yang Hong,
Aydın Mehtap,
Alkurt Gizem,
Kim Woonghee,
Akyol Dogukan,
Zhang Cheng,
DinlerDoganay Gizem,
Turkez Hasan,
Shoaie Saeed,
Nielsen Jens,
Borén Jan,
Olmuscelik Oktay,
Doganay Levent,
Uhlén Mathias,
Mardinoglu Adil
Publication year - 2021
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202101222
Subject(s) - nad+ kinase , glutathione , nicotinamide , carnitine , placebo , pharmacology , nicotinamide adenine dinucleotide , metabolome , metabolism , medicine , chemistry , biochemistry , metabolite , enzyme , pathology , alternative medicine
COVID‐19 is associated with mitochondrial dysfunction and metabolic abnormalities, including the deficiencies in nicotinamide adenine dinucleotide (NAD + ) and glutathione metabolism. Here it is investigated if administration of a mixture of combined metabolic activators (CMAs) consisting of glutathione and NAD+ precursors can restore metabolic function and thus aid the recovery of COVID‐19 patients. CMAs include l ‐serine, N ‐acetyl‐ l ‐cysteine, nicotinamide riboside, and l ‐carnitine tartrate, salt form of l ‐carnitine. Placebo‐controlled, open‐label phase 2 study and double‐blinded phase 3 clinical trials are conducted to investigate the time of symptom‐free recovery on ambulatory patients using CMAs. The results of both studies show that the time to complete recovery is significantly shorter in the CMA group (6.6 vs 9.3 d) in phase 2 and (5.7 vs 9.2 d) in phase 3 trials compared to placebo group. A comprehensive analysis of the plasma metabolome and proteome reveals major metabolic changes. Plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly improved in patients treated with CMAs as compared to placebo. The results show that treating patients infected with COVID‐19 with CMAs lead to a more rapid symptom‐free recovery, suggesting a role for such a therapeutic regime in the treatment of infections leading to respiratory problems.