Bmal1 and Gut-lung axis in SARS-CoV-2 infection: New insight into the effects of melatonin on COVID-19 patients?

Coronavirus disease 2019 (COVID-19), is known as one of the most known challenge worldwide. Numerous studies have tried to introduce different mechanisms involved in the pathophysiology of COVID-19 and efforts in this field are also ongoing. The presence of SARS-CoV-2 RNA in feces of COVID-19 patients along with a variety of gastrointestinal symptoms may show a significant association between gut microbiota and SARS-CoV-2 infection. However, the exact mechanism indicating how SARS-CoV-2 and gut flora influence each other remains unknown. This paper aims to introduce a possible molecular mechanism based on recent findings on the association between circadian rhythm and gut flora in COVID-19 patients to express a new insight into the probable mechanism of melatonin in protection against SARS-CoV-2 infection.

Potential effects of icariin, the Epimedium-derived bioactive compound in the treatment of COVID-19: a hypothesis.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected the world's health systems for more than two years. This disease causes a high mortality rate followed by cytokine storm-induced oxidative stress and acute respiratory distress syndrome (ARDS). Therefore, many drugs have been considered with emphasis on their anti-inflammatory and antioxidant effects in controlling the consequences of SARS-CoV-2 infection. Icariin is a major bioactive pharmaceutical compound derived from Epimedium plants, which is known due to its anti-inflammatory and antioxidant effects. Additionally, the protective effects of icariin have been studied in different pathologies through modulating intracellular pathways. In addition to the potential effect of this compound on inflammation and oxidative stress caused by SARS-CoV-2 infection, it appears to interfere with intracellular pathways involved in viral entry into the cell. Therefore, this paper aims to review the molecular mechanisms of anti-inflammatory and antioxidant properties of icariin, and hypothesizes its potential to inhibit SARS-CoV-2 entry into host cells through modulating the intracellular pathways.

Potential effects of icariin, the Epimedium-derived bioactive compound in the treatment of COVID‐19: a hypothesis

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected the world’s health systems for more than two years. This disease causes a high mortality rate followed by cytokine storm–induced oxidative stress and acute respiratory distress syndrome (ARDS). Therefore, many drugs have been considered with emphasis on their anti-inflammatory and antioxidant effects in controlling the consequences of SARS-CoV-2 infection. Icariin is a major bioactive pharmaceutical compound derived from Epimedium plants, which is known due to its anti-inflammatory and antioxidant effects. Additionally, the protective effects of icariin have been studied in different pathologies through modulating intracellular pathways. In addition to the potential effect of this compound on inflammation and oxidative stress caused by SARS-CoV-2 infection, it appears to interfere with intracellular pathways involved in viral entry into the cell. Therefore, this paper aims to review the molecular mechanisms of anti-inflammatory and antioxidant properties of icariin, and hypothesizes its potential to inhibit SARS-CoV-2 entry into host cells through modulating the intracellular pathways.

Hesperetin and the PI3K/AKT pathway: Could their interaction play a role in the entry and replication of the SARS-CoV-2?

Hesperetin, mainly found in citrus honey, has antioxidant, anti-inflammatory, and antiviral properties. Recently, the effect of hesperetin on different aspects of SARS-CoV-2 infection such as viral entry, replication, and inflammatory responses has attracted a lot of attention. However, the exact molecular mechanism for its effects on SARS-CoV-2 infection is not stated. The PI3K/AKT signaling pathway is an intracellular pathway involved in cell proliferation, protein synthesis, and response to environmental changes. Since the role of this pathway in the pathogenesis of SARS-CoV-2 has recently been considered, this letter assumes the probable role of this pathway in the function of hesperetin against SARS-CoV-2 infection. PRACTICAL APPLICATIONS: In this paper, we have discussed the therapeutic effects of hesperetin on SARS-CoV-2 infection. Additionally, we have hypothesized the molecular mechanism of hesperetin in suppression of SARS-CoV-2 entry to the host cells, its replication and inhibition of inflammatory responses. Based on this evidence, the pharmacological properties of hesperetin make this natural compound a potential treatment for suppression of SARS-CoV-2 entry into host cells and the subsequent replication of viral particles.

The probable role and therapeutic potential of the PI3K/AKT signaling pathway in SARS-CoV-2 induced coagulopathy.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is associated with a high mortality rate. The majority of deaths in this disease are caused by ARDS (acute respiratory distress syndrome) followed by cytokine storm and coagulation complications. Although alterations in the level of the number of coagulation factors have been detected in samples from COVID-19 patients, the direct molecular mechanism which has been involved in this pathologic process has not been explored yet. The PI3K/AKT signaling pathway is an intracellular pathway which plays a central role in cell survival. Also, in recent years the association between this pathway and coagulopathies has been well clarified. Therefore, based on the evidence on over-activity of the PI3K/AKT signaling pathway in SARS-CoV-2 infection, in the current review, the probable role of this cellular pathway as a therapeutic target for the prevention of coagulation complications in patients with COVID-19 is discussed.

The probable mechanism of reduced androgen level in COVID-19 patients.

COVID-19, caused by the SARS-CoV-2, has challenged the health care systems of the world. Although the pulmonary complications of the infection have received extensive attention, addressing the other complications (e.g., changes in androgen levels) could further provide a more efficient understanding of the disease, which might aid in combating it. Since the association between androgens and the expression and activity of SARS-CoV-2 receptors has been proven and anti-androgen-based therapies have been considered in this regard, addressing various aspects of androgen level changes can be constructive. The present paper examines the possible mechanisms of changes in androgen levels by the virus. It seems that the infection of the gonads by the SARS-CoV-2 could reduce the androgen levels by affecting different cellular pathways.

Azithromycin: Immunomodulatory and antiviral properties for SARS-CoV-2 infection.

Azithromycin, a member of the macrolide family of antibiotics, is commonly used to treat respiratory bacterial infections. Nevertheless, multiple pharmacological effects of the drug have been revealed in several investigations. Conceivably, the immunomodulatory properties of azithromycin are among its critical features, leading to its application in treating inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Additionally, azithromycin may directly inhibit viral load as well as its replication, or it could demonstrate indirect inhibitory impacts that might be associated with the expression of antiviral genes. Currently, coronavirus disease 2019 (COVID-19) is an extra urgent issue affecting the entire world, and it is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Acute respiratory distress syndrome (ARDS), which is associated with hyper inflammation due to cytokine release, is among the leading causes of death in COVID-19 patients with critical conditions. The present paper aims to review the immunomodulatory and antiviral properties of azithromycin as well as its potential clinical applications in the management of COVID-19 patients.