Fusion Peptide activating protease (cellular host’s TMPRSS2) inhibitor:
Innate or Adaptive Immune System Modulators
- Dexamethasone for stage 4 or greater COVID-19 Infection (Patients requiring a ventilator or in ICU) Anti-inflammatory via agonist of the cortisol receptor.
- Nebulized interferon beta 1 enhances innate antiviral immunity but interferon alpha increases ACE-2 receptor expression and is an indicator of severe progression of disease.
- Merck’s MK-7011/SACCOVID/CD25Fc
Inhibitors of Cytokine Storm/Immune Hyperactivity , Inflammation, or Netosis:
- GM-CSF inhibitor (Humanigen’s lenzilumab and Kiniksa Pharmaceuticals’ mavrilimumab )
- Cortisol, CCR3 Inhibitor, TNF-alpha Receptor Blocker, Complement C5inhibitors + CD14 blockers will inhibit Toll Receptor Signaling , Immune rejection suppressors, Jak1/Jak2 inhibitors and inhibitors of endocytosis ( baricitinib) , and others
Other pending vaccines for antibody mediated or CD8 killer cell based immunity.
- Astrazeneca – Oxford University– ChAdOx1-nCoV-19 ( 70% to 90% effective with 2 shots 1 month apart )
- Glaxo adjuvant with Sanofi, Clover, or Medicago Antigen
- Innovio Pharmaceuticals,
- CanSino Biologics,
- Shenzhen Geno-Immune Medical Institute,
Autophagy stimulator :
- Niclosamide (inhaled) or clinical trials by ANA Therapeutics, MK2206, and Spermidine
Inhibiting Viral protein chaperone GRP78 and increasing autophagosome formation:
Block viral entry at the endosomal stage by inhibiting phosphatidyl inositol 3,5 or 5 synthesis or effecting local zinc release from the fyve domain.
- PIKfyve kinase inhibitor apilimod
Cysteine protease inhibitors MDL-28170, Z LVG CHN2, VBY-825, and ONO 5334. Effect endosomal processing/entry of the virus into the cell. (Perhaps by inhibiting fusion peptide activating enzymes.
Inhibiting the Alternative Complement Pathway by inhibiting Factor D.
Increasing cellular cholesterol biosynthesis with agents like amlodipine. possibly effecting ORP1L Cholesterol sensing, tethering, and endosomal transport.
Inhibiting Endosomal Acidification , Recycling and/or Viral Intra-Vesicular Transport/Release to the Surface Membrane via effects on Retromer, PIKC3C3, and Commander.
Inhibiting Viral RNA transcription (SLTM, STEN), translation, ER viral protein processing, or Golgi viral protein Glycosylation/DeGylcosylation/mannosidase.
Inhibiting Viral RNA – host protein interactions required for the viral life cycle. PPIA (cyclosporin A); ARP2(CK-548); ATP1A1(oubain); DDX3X() , mTORC1 phosphorylation of LARP1
Stimulating intrinsic antiviral activity by DEAD-box RNA helicase DDX42 , Mx1 , CNBP, or LARP1
Nutritional : ( broccoli sprouts – sulforaphane), Vitamin D, Vitamin B6, Vitamin B1, Spermidine and Wellness Formula as prophylactics .