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Minocycline in Combination With/Without Azithromycin As a Potential Treatment in Covid-19 Suspected Or Infected Patients

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Minocycline in Combination With/Without Azithromycin As a Potential Treatment in Covid-19 Suspected Or Infected Patients EAS Journal of Parasitology and Infectious Diseases Abbreviated Key Title: EAS J Parasitol Infect Dis ISSN: 2663-0982 (Print) & ISSN: 2663-6727 (Online) Published By East African Scholars Publisher, Kenya Volume-2 | Issue-2 |Mar-Apr 2020 | DOI: 10.36349/EASJPID.2020.v02i02.001 Research Article Minocycline in Combination With/Without Azithromycin as a Potential Treatment in Covid-19 Suspected or Infected Patients "Moh'd Nour" Mahmoud Bani Younes PhD*1, Jaafar Abd Alrahman Abu Abeeleh PhD1, Sarah Hassan Sharaya Pharm D2, Eman Feras Awwad Pharm D2, Zahra Amjad AL-Masalha Pharm D2 & Saba Mohammed Amro Pharm D2. 1Clinical Pharmacy Department,King Hussein Medical Hospital,Royal Medical Services,Amman,Jordan 2Clinical Pharmacy Department,The University of Jordan, Amman, Jordan Abstract: The pandemic coronavirus disease which has started in 2019 (COVID-19) in Article History Wuhan China, is the major humanity concern nowadays. COVID-19 causes Acute Received: 24.03.2020 Respiratory Distress Syndrome (ARDS) after cytokine storm is pursuing and elderly are the Accepted: 14.04.2020 Published: 17.04.2020 most susceptible. Efforts are made to find a vaccination or a treatment for COVID-19 infection. Due to lack of adequate evidence, no anti-SARS-CoV-2 drug or vaccine has been Journal homepage: approved officially, yet. Drug repurposing is at the essence of this battle and since https://www.easpublisher.com/easjpid Minocycline has a preferable safety profile and high tolerability, it can be a great tool to the treatment regimens applied. Minocycline has demonstrated antiviral and Quick Response Code immunomodulatory activity that is independent of its antibacterial activity. Additionally, the proposed combination with Azithromycin enhances the anti-inflammatory effects of Minocycline which is necessary for a fighting off an excessive cytokine storm response. Some researchers reported effective therapeutic options. On the other hands, there use was limited either because of severe side effects or high cost. In this review article we shall go over recent researches that would support the usage of Minocycline in combating the Coronavirus (SARS-CoV-2) outbreak. Further efforts are require to developing the safest and most effective approach to decrease mortality rate in suspected population and severe case. Keywords: Azithromycin, COVID-19, Immuno-Modulator, Hydroxychloroquine, Minocycline. Copyright © 2020 The Author(s): This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY-NC 4.0) which permits unrestricted use, distribution, and reproduction in any medium for non-commercial use provided the original author and source are credited. NTRODUCTION I One of the drugs to be repurpose is In light of the most recent viral outbreak, the Minocycline. Minocycline semi-synthetic second Severe Acute Respiratory Syndrome Coronavirus-2 generation tetracycline has antibacterial activity and (SARS-CoV-2), the world is at a frantic race to find a approved for use in gram negative or gram positive treatment for such a rapidly spreading infectious infections. It is recommended for anthrax, disease. This novel coronavirus disease 2019 (COVID- meningococcal carrier state, respiratory tract infections 19) has a higher transmissibility from human to human and many other infections. It is of great interest due to compared with SARS-CoV-1, that’s make it global its displayed anti-inflammatory, antioxidant, anti- challenging, despite of its lower pathogenicity apoptotic and immune modulatory effects. Additionally, compared with SRS-CoV-1. Considering it’s already at it has been shown to have in-vitro antiviral activity pandemic status, it comes as no surprise that the number against different viral infections namely: Human of confirmed cases has reached a staggering 575,444 (as Immunodeficiency Virus (HIV), Japanese of 28/3/2020) worldwide and is still expected to Encephalopathy Virus (JEV), West Nile Virus (WNV), increase. Because of growing understanding of SARS- and the Influenza Virus. Also, Minocycline has been CoV-2 in the virology, epidemiology and clinical shown to have in-vitro/in-vivo activity against management strategies and its high transmissibility, Enterovirus 71 (EV71) brainstem encephalitis (BE) researchers study older anti-viral and anti-microbial (Dutta, K., & Basu, A. 2011). The second agent is agents effectiveness instead of developing new ones. Azithromycin (Azalide/Macrolide family) which has However, no anti-SARS-CoV-2 drug or vaccine has antibacterial and anti-inflammatory effect, used for been officially approved due to the absence of adequate community acquired pneumonia, upper respiratory tract evidence. As a result, the most viable option showcased infection and many other bacterial infections. Even the to us, during this period, is drug repurposing. evidences of using Minocycline and Azithromycin are *Corresponding Author: "Moh'd Nour" Mahmoud Bani Younes Email: [email protected] 8 "Moh'd Nour" Mahmoud Bani Younes. et al., EAS J Parasitol Infect Dis; Vol-2, Iss-2 (Mar-Apr, 2020): 8-11 low, Its combination with Azithromycin could be mediated cytopathic effects, in vitro, 7-14 days post warranted and a further rigorous preclinical models and infection. Later on, it was further reported to have clinical trials are necessary. In this minireview, we aim significant anti-inflammatory and neuroprotective to summarize the updated potential advantages of activity in a simian immunodeficiency virus (SIV) Minocycline with or without Azithromycin compared model of HIV associated central nervous system (CNS) with Hydroxychloroquine (HCQ) (Gautam,C.S., & disease. Such effects are due to various modes of action Aulakh, R. 2020). of Minocycline from suppression of cellular activation of CD4+ T-cells to inhibition of activation of apoptosis ISCUSSION signal-regulating kinase-1 (ASK1). Neuroprotective and D anti-inflammatory effect on microglia of minocycline The pathogenesis of the coronavirus has yet to made it effective for dementia caused by Acquired be fully understood, with only hypotheses present to Immunodeficiency Syndrome (AIDS). Suppression of give us an idea of what we’re dealing with. According lymphocyte and macrophages HIV and SIV retroviruses to the latest findings, it has been shown that SARS- replication in vivo, was also reported (Nagarakanti, S., CoV-2 has lower pathogenicity but higher & Bishburg, E. 2015). transmissibility from human to human when compared to its former counterpart SARS-CoV-1. The major Apart from its efficacy against retroviruses, concern of SARS-CoV-2 pathogenesis is the severe Minocycline is also effective against flaviviral alveolar damage after alveolar cells type-II preferential infections. A study published in 2007 claimed that attacking which ultimately causing Acute Respiratory minocycline significantly inhibited West Nile virus Distress Syndrome (ARDS) with varying severities replication in cultured human neuronal cells and depending primarily on patient’s immune competency subsequently prevented virus-induced apoptosis. Its and cytokine storm status. Considering the possible antioxidant properties are underlined in an in-vitro lympho-depleting effect of the disease at its early study conducted on neuro-blastoma cells infected with stages, will dictate whether a patient’s immune system the Japanese Encephalopathy Virus (JEV) where can ward off the virus or not. Moreover causing hyper Minocycline was shown to significantly reduce the inflammatory condition of high concentration of oxidative stress caused by the infection. The pleiotropic cytokines was seen in Intensive Care Unit (ICU) effects of Minocycline like neuroprotection, anti- patients’ more than non ICU patients. After COVID-19 inflammation, and protection against oxidative stress infection, CD-4 T cells are rapidly activated and are independent of its antibacterial action. When produce granulocyte-macrophage colony stimulating considering the reasoning behind using Minocycline for factor (GM-CSF) and inflammatory cytokines and the treatment of the Coronavirus, the intended higher expression of interleukin 6 (IL-6), tumor mechanism of action is to suppress the excessive necrosis factors (TNF), and interleukin-8 (IL-8) (Lin, L. inflammatory response that is taking place. Recent data et al., 2020). The most noticeable manifestations of the has shown that ICU patients had higher cytokine levels COVID-19 is a marked increase in these inflammatory when compared to non-ICU patients infected with the cytokines which can develop into a more severe and coronavirus. They also had higher percentages of GM- deadly case of cytokine storm. Thus, suppression of CSF, IL-6, and CD4+ T-cells. Such findings lead us in these pro-inflammatory mediators, or in other words, the direction of associating cytokine levels with disease rebalancing the imbalance between the pro- severity. inflammatory and anti-inflammatory mediators can be a viable options for mitigating this cytokine storm (Li, H. A study titled anti-inflammatory and antiviral et al., 2020). effects of Minocycline in Enterovirus 71 infections (EV71) concluded that minocycline can be considered With that being said, Minocycline’s high as novel approach in treating or controlling enterovirus safety index alongside its proven long-term tolerability neurological complications. In this study, Minocycline both make it a good candidate for repurposing. reduced cytopathic effects (CPEs), viral protein Additionally, it has better a pharmacokinetic
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