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A Combo Compound Therapy Effectively Reduces SARS-CoV-1 ViralLoad in Mouse Lung

ABSTRACT

Objective: SARS-CoV disease caused by SARS-CoV-1 is of multifactorial etiology consisting of upstream and downstream phases. The upstream phase is the physical breach of the cells protective shield by extraneous stressors including the virus and environmental elements (xeno), while the downstream is a sequela of damages (plexic)

manifested in various symptoms, herein called xenoplexic diseases. Symptom targeting drugs are ineffective andpalliative at best. SARS-CoV is a xenoplexic disease best treated with a combo therapeutic strategy This study evaluates Embotricin™ (EMB), a multicomponent compound, to treat SARS-CoV.


Materials and methods: Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-1), strain Urbani (200300592), obtained from the Centers for Disease Control and Prevention (CDC, Atlanta, GA) was used as the test virus. Female BALB/C mice obtained from Charles River Laboratories (Wilmington, MA) were the animal host. New Chemical Entities (NCE) including FTX-214, FTX-218, and FTX-219 were formulated as a 3-component combo, herein called Embotricin (EMB). Also, a 4-component compound consisting of EMB plus sodium thiosulfate was evaluated. The 3- and 4-combo compounds were administered 2 days prior to infection, given by per os (PO) daily (q.d.) for 5 days. Poly I:C, a known antiviral compound acting as an immunomodulator was used as a comparative

control, administered intraperitoneally (IP).


Results: EMB at 3.1 mg/kg fixed dose (1:1:1 ratio) combo reduced viral load by 14.4% compared to 11.8% for poly I:C at 10 mg/kg dose. Addition of sodium thiosulfate (4-combo formulation) further boosted the activity to 16.6%.

Increasing the 4-combo dosages to 4.65 mg/kg and 6.2 mg/kg further increased activity to 18.2% and 20.9%, respectively.


Conclusion: The individual components synergistically targeted the upstream disease etiology and restore in toto the health of the cell to ward off SARS-CoV-1. Thus, combo therapy may well be a universal platform to treat xenoplexic diseases where monotherapies fail. The combo therapy effectively reduced the viral load of SARS-CoV-1, not by directly inhibiting the virus, but most likely due to enhancing the health of the cell.

Keywords: Xenoplexic disease; Combo therapy; SARS-CoV-1; Glycocalyx; Reactive Oxygen Species (ROS); Particulate Matters (PMs); ACE2 receptors; Heparan sulfate; Cellular-humoral immunity.

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