Melatonin: highlighting its use as a potential treatment for SARS-CoV-2 infection

Abstract

Numerous pharmaceutical drugs have been repurposed for use as treatments for COVID-19 disease. These drugs have not consistently demonstrated high efficacy in preventing or treating this serious condition and all have side effects to differing degrees. We encourage the continued consideration of the use of the antioxidant and anti-inflammatory agent, melatonin, as a countermeasure to a SARS-CoV-2 infection. More than 140 scientific publications have identified melatonin as a likely useful agent to treat this disease. Moreover, the publications cited provide the rationale for the use of melatonin as a prophylactic agent against this condition. Melatonin has pan-antiviral effects and it diminishes the severity of viral infections and reduces the death of animals infected with numerous different viruses, including three different coronaviruses. Network analyses, which compared drugs used to treat SARS-CoV-2 in humans, also predicted that melatonin would be the most effective agent for preventing/treating COVID-19. Finally, when seriously infected COVID-19 patients were treated with melatonin, either alone or in combination with other medications, these treatments reduced the severity of infection, lowered the death rate, and shortened the duration of hospitalization. Melatonin’s ability to arrest SARS-CoV-2 infections may reduce health care exhaustion by limiting the need for hospitalization. Importantly, melatonin has a high safety profile over a wide range of doses and lacks significant toxicity. Some molecular processes by which melatonin resists a SARS-CoV-2 infection are summarized. The authors believe that all available, potentially beneficial drugs, including melatonin, that lack toxicity should be used in pandemics such as that caused by SARS-CoV-2.

Melatonin as an Anti-Aging Therapy for Age-Related Cardiovascular and Neurodegenerative Diseases

“…In this regard, it has been demonstrated that daily bedtime administration of 3-12 mg of melatonin is effective in the treatment of sleep behavior disorders and may stop or slow neurodegeneration associated with these diseases. However, if doses of melatonin that have been effective in animal models to reduce not only sleep disorders but also the symptomatology of PD are projected to humans, these would be in the range of 40-100 mg/day, a dose that is consistent with studies in which melatonin was used to inhibit COVID-19 infections (Reiter et al, 2022). Clearly, clinical studies using this dose range are urgently needed to provide information on the optimal dose of melatonin for human use in relation to the treatment of symptomatology of this and other neurodegenerative diseases (Cardinali, 2019;Pérez-Lloret and Cardinali, 2021).…”

A Review of the Potential Effects of Melatonin in Compromised Mitochondrial Redox Activities in Elderly Patients With COVID-19

“…When patients severely infected with COVID-19 were treated with melatonin, the severity of infection, mortality, and length of hospitalization were reduced. Of note, melatonin has a high safety profile at a broad dose range and is not highly toxic ( 267 ). Consequently, we encourage the consideration of the use of melatonin as a countermeasure to SARS-CoV-2 infection.…”

Melatonin use for SARS‐CoV‐2 infection: Time to diversify the treatment portfolio

“…Repurposed drugs are used as treatments with variable success but newly‐developed medications are becoming available which may provide greater efficacy against COVID‐19. 9 The active ingredient of the newly‐developed Pfizer drug, paxlovid, is nirmatreliv, a Mpro inhibitor. Mpro is a major protease of SARS‐CoV‐2 which mediates viral replication and transcription.…”

“…Besides clinical trials, and so forth, which indicate that melatonin is effective in aiding the recovery of COVID patients, measured by any parameter considered, there is a vast amount of experimental information (150 publications to date) which clarifies why it is effective. 9 , 11 Melatonin is a powerful antioxidant and anti‐inflammatory molecule that modifies the innate immune system and functions as a pan‐antiviral agent. 12 Melatonin lowers virus uptake into cells and hinders their replication, inhibits sepsis, reduces phospholipase A2 levels, lowers inflammatory cytokines, and so forth, which contribute to acute respiratory disease and systemic multiorgan dysfunction (Figure 1 ).…”