Penta-therapy Protocol for Omicron BA.2.12.1, BA.2.75 and BA.5
Multi-drugs with Multiple Mechanisms
การรักษาติดเชื้อ COVID-19 ด้วยยาหลายตัวร่วมกันที่ออกฤทธิ์ช่วยยับยั้งหลายๆกลไก Mechanisms of action ในการเกิดโรค Pathogenesis และการดำเนินของโรค Progression of Disease
1.1 Ivermectin binds to S-Protein with high affinity (tightly).
1.2 Ivermectin inhibits ACE2:S1 binding and TMPRSS:S2 fusion.
1.3 Ivermectin inhibits RNA-dependent RNA polymerase.
1.4 Ivermectin blocks viral proteins: ORF-3a, NSP-1 and ODR-6.
1.5 Ivermectin inhibits activation of NF-Kb and MAP3 Kinase.
1.6 Ivermectin decreases expression of pro-inflammatory cytokines and chemokines.
1.7 Ivermectin prevents the binding of IMPα to the N binding site. Consequently, N would not perform its nuclear activity which is thought to suppress the host immune response and sequester ribosomal subunits, mechanisms which are thought to abrogate sufficient viral replication.
2.1 Fluoxetine reduces serotonin uptake by platelets.
2.2 Fluoxetine reduces histamine release from mast cells.
2.3 Fluoxetine interferes lysosomal trafficking of virus.
2.4 Fluoxetine interferes with lysosomal membrane binding of ASM.
2.5 Fluoxetine activation of S1R inhibits IRE-1-mediated inflammation.
2.6 Fluoxetine inhibits melatonin degradation.
2.7 Fluoxetine inhibits NF-kappa B and IL-6 pathway resulting in inhibition of cytokine storm and inflammatory response.
2.8 Fluoxetine inhibits SARS-CoV-2 in human lung tissue.
3.1 Bromhexine is a specific TMPRSS2 inhibitor that potentially inhibits the infectivity cycle of SARS-CoV-2. TMPRSS2 is a protease that has a key role in the entry of SARS-CoV-2 into host cells.
4.1 Niclosamide can block endocytosis of SARS-CoV-2 by being PH dependent,
which inhibit endosomal acidification.
4.2 Niclosamide can prevent autophagy of SARS-CoV-2 by inhibition of S-Phase
kinase associated protein 2 (SKP2).
4.3 Niclosamide reverses SARS-CoV-2 control of lipophagy.
4.4 Niclosamide, an inhibitor of TMEM16F, has been shown to block spike-dependent syncytia formation and effects on SARS-CoV-2 entry.
4.5 Niclosamide inhibits mitochondrial oxidative phosphorylation with subsequent depletion of intracellular ATP, which trigger adenosine monophosphate protein kinase (AMPK) which directly blocks mTOR signaling pathway.
4.6 Niclosamide inhibits on the SARS-CoV-2-mediated inflammatory signaling pathways and release of proinflammatory cytokines: SARS-CoV-2 through activation of macrophage, mammalian target of rapamycin (mTOR) and signal transducer and activator transcription 3 (STAT-3) leads to macrophage activation syndrome (MAS), cell apoptosis, and activation release of plasminogen activator inhibitor-1(PAI-1) respectively.
5.1 Doxycycline inhibits metalloproteinases (MMPs)
5.2 Doxycycline inhibits papain-like proteinase (PLpro) that mediates the generation of non-structural proteins (NSPs 1–3) by cleavage of the replicase polyprotein. These NSPS have a crucial role in viral replication.
5.3 Doxycycline by inhibiting 3C-like main protease (3CLpro) also has a role in the formation of more NSPs (4–16) / maturation, all are essential in the virus replication.
5.4 Doxycycline is suggested to act as an ionophore that, increasing Zin intracellular concentrations, which has a role suppressing viral replication in addition to other roles in enhancing the immune system.
5.5 Doxycycline inhibits the critical inflammatory mediator of the senescence-associated secretory phenotype (SASP), namely IL-6 that responsible for most serious complications of viral infection.
5.6 Low-dose of doxycycline inhibits expression of CD147/EMMPRIN that may have a role in the viral entry into T lymphocytes.
1. The mechanisms of action of ivermectin against SARS-CoV-2—an extensive review
2. Repurposing Ivermectin for COVID-19: Molecular Aspects and Therapeutic Possibilities
3. Ivermectin Pharmacological Considerations
1. Mechanisms of action of fluvoxamine for COVID-19: a historical review
2. Fluvoxamine: A Review of Its Mechanism of Action and Its Role in COVID-19
3. Fluoxetine as an anti-inflammatory therapy in SARS-CoV-2 infection
4. Potential Role of the Antidepressants Fluoxetine and Fluvoxamine in the Treatment of COVID-19
5. The serotonin reuptake inhibitor Fluoxetine inhibits SARS-CoV-2 in human lung tissue
1. Bromhexine is a potential drug for COVID-19; From hypothesis to clinical trial
2. Bromhexine Hydrochloride: Potential Approach to Prevent or Treat Early Stage Novel 2019 Coronavirus Disease
3. Potential new treatment strategies for COVID-19: is there a role for bromhexine as add-on therapy?
1. Niclosamide-A promising treatment for COVID-19
2. Drugs that inhibit TMEM16 proteins block SARS-CoV-2 spike-induced syncytia
3. Niclosamide reverses SARS-CoV-2 control of lipophagy
4. Plausible mechanisms of Niclosamide as an antiviral agent against COVID-19
5. Niclosamide for Covid-19: bridging the gap
1. Pharmacological basis for the potential role of Azithromycin and Doxycycline in management of COVID-19
2. Repurposing of Doxycycline to Hinder the Viral Replication of SARS-CoV-2: From in silico to in vitro Validation
3. Tetracycline and viruses: a possible treatment for COVID-19?
4. Pleiotropic Effects of Tetracyclines in the Management of COVID-19: Emerging Perspectives
5. Doxycycline as a potential partner of COVID-19 therapies