Melatonin and REGN-CoV2 combination as a vaccine adjuvant for Omicron variant of SARS-CoV-2.

The omicron variant (B.529) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in late 2021, caused panic worldwide due to its contagiousness and multiple mutations in the spike protein compared to the Delta variant (B.617.2). There is currently no specific antiviral available to treat Coronavirus disease 2019 (COVID-19). However, studies on neutralizing monoclonal antibodies (mAb) developed to fight COVID-19 are growing and gaining traction. REGN-COV2 (Regeneron or imdevimab-casirivimab combination), which has been shown in recent studies to be less affected by Omicron's RBD (receptor binding domain) mutations among other mAb cocktails, plays an important role in adjuvant therapy against COVID-19. On the other hand, it is known that melatonin, which has antioxidant and immunomodulatory effects, can prevent a possible cytokine storm, and other severe symptoms that may develop in the event of viral invasion. Along with all these findings, we believe it is crucial to evaluate the use of melatonin with REGN-COV2, a cocktail of mAbs, as an adjuvant in the treatment and prevention of COVID-19, particularly in immunocompromised and elderly patients.

The circadian clock gene Bmal1: Role in COVID-19 and periodontitis.

The physiological processes of most living organisms follow a rhythmic pattern, which is controlled by the interaction between environmental cues and the internal circadian timing system. Different regulatory circadian genes are expressed in most cells and tissues, and disruptions in the sleep-wake cycle affect these genes, which may result in metabolic disorders and cause alterations of the immune system. The manifestations of these disrupted genes are evident in inflammatory conditions such as periodontitis and some viral diseases, including COVID-19. The brain and muscle ARNT-like protein-1 (Bmal1), an important circadian regulatory gene, decreases when the sleep-wake cycle is disrupted. Circadian genes have been linked to different events, including cytokine storm in inflammatory conditions and virus invasion. The evaluation of the effects of these regulatory circadian genes, especially Bmal1, in periodontitis and viral infection suggests that both diseases may have a common pathogenesis via the NF-κB pathway. This brief review highlights the role and importance of the circadian clock gene Bmal1 in the disease process of periodontitis and suggests its role and importance in viral infections, including COVID-19.

Role of NLRP3 inflammasome in COVID-19 and periodontitis: Possible protective effect of melatonin.

Daily new information emerges regarding the COVID-19, infection of SARS-CoV-2, which is considered a global pandemic. Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) are required to complete the viral invasion pathway and are present in the oral mucosa, gingiva and periodontal pocket. Thus, increasing the likelihood of periodontitis and gingivitis caused by COVID-19. The cytokine storm during COVID-19 similarly arises during periodontal inflammation. Studies have reported that NOD-Like Receptor family pyrin domain-containing 3 (NLRP3) inflammasome is significant in the cytokine storm. Recently, the course of the COVID-19 has been related to the melatonin levels in both COVID-19 and periodontal diseases. It is known that melatonin prevents the activation of NLRP3 inflammasome. In light of these findings, we think that melatonin treatment during COVID-19 or periodontal diseases may prevent the damage seen in periodontal tissues by preventing the activation of NLRP3 inflammasome.

Daylight is critical to preserve 5-methoxytryptophol levels in suspected and confirmed COVID-19 patients.

Declared as a pandemic by the World Health Organization, COVID-19 causes damage to tissues with the cytokine storm. It even causes death in people who are fond of it. In this case, the role of the immune system is vital. In particular, the cycle of melatonin and 5-methoxytryptophol released from the pineal hormone ensures that immunity continues for 24 h. While 5-MTX is active in sunlight, melatonin secretion increases in the dark at night. 5-MTX, like melatonin, has shown antioxidant and immunomodulatory properties in studies. Therefore, people who are sick and those who are not must strictly comply with the 24-h circadian rhythm during this period. We think that it is crucial in terms of being protected from the disease that we should carry out our activities according to the circadian rhythm.

Role of melatonin in the treatment of COVID-19; as an adjuvant through cluster differentiation 147 (CD147).

COVID-19 caused by the SARS-CoV-2 outbreak quickly has turned into a pandemic. However, no specific antiviral agent is yet available. In this communication, we aimed to evaluate the significance of CD147 protein and the potential protective effect of melatonin that is mediated by this protein in COVID-19. CD147 is a glycoprotein that is responsible for the cytokine storm in the lungs through the mediation of viral invasion. Melatonin use previously was shown to reduce cardiac damage by blocking the CD147 activity. Hence, melatonin, a safe drug, may prevent severe symptoms, reduce symptom severity and the adverse effects of the other antiviral drugs in COVID-19 patients. In conclusion, the use of melatonin, which is reduced in the elderly and immune-compromised patients, should be considered as an adjuvant through its CD147 suppressor and immunomodulatory effect.