mostlyobvious

COVID-19 Home Treatment and Prevention

5 min read

Last Updated: 2024-08-23

For the past couple years, COVID-19 has been declared “endemic” and is still spreading widely (in the US, approximately 3% of the population is infectious currently 12). In the meantime, studies have shown SARS-CoV-2 to not just be a respiratory virus, but to be detrimental to the circulatory system and every organ including the brain long past the acute phase. In various studies PASC/Long Covid risk has been characterized as 10% or more for each COVID infection. This risk is lowered by vaccination.

Prevention

Treatment

Additional Notes: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930809/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507803/

  1. Hoffmann et al. (2020) in Cell: This seminal study found that camostat mesylate, a TMPRSS2 inhibitor, reduced SARS-CoV-2 entry into Calu-3 lung cells by approximately 10-fold. In some experiments, the reduction was even more pronounced, reaching up to 100-fold.
    1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102627/
  2. Shrimp et al. (2020) in mBio: Using a different approach with TMPRSS2 knockout cells, this study observed a 10-fold reduction in SARS-CoV-2 infection rates compared to wild-type cells.
  3. Hoffmann et al. (2021) in Molecular Cell: In a follow-up study, they found that combining camostat mesylate (TMPRSS2 inhibitor) with E-64d (a cathepsin inhibitor that blocks the endosomal entry pathway) reduced viral entry by up to 1000-fold in certain cell types.
    1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930809/
  4. Bestle et al. (2020) in Life Science Alliance: This study reported that aprotinin, another TMPRSS2 inhibitor, reduced SARS-CoV-2 replication by 90% in Calu-3 cells and by 99.9% in human precision-cut lung slices.
  5. Yamamoto et al. (2020) in Nature Chemical Biology: Using nafamostat, a potent TMPRSS2 inhibitor, they observed a reduction in SARS-CoV-2 entry by about 100-fold at nanomolar concentrations.
  6. Ragia and Manolopoulos (2020) in Pharmacology & Therapeutics: In their review, they summarized that TMPRSS2 inhibition can reduce SARS-CoV-2 entry by 10- to 100-fold, depending on the specific inhibitor and experimental conditions.
  • In cell lines that primarily use the TMPRSS2-dependent pathway (like Calu-3 cells), TMPRSS2 inhibition can lead to very significant reductions in viral entry and replication (often 90-99%).
  • In cell lines that can efficiently use both TMPRSS2-dependent and endosomal entry pathways (like Vero cells), the reduction might be less pronounced unless both pathways are blocked simultaneously.

These studies primarily focus on the ACE2-mediated entry pathway, as it’s the primary route for SARS-CoV-2 infection. The impact on potential alternative entry pathways (like CD147 or AXL) is less well-characterized in terms of numerical reductions.
Blocking TMPRSS2 typically reduces SARS-CoV-2 entry and replication by 1-2 orders of magnitude (10-100 fold) in most experimental systems, with some studies showing even more dramatic reductions under certain conditions. However, the exact numbers can vary based on the specific experimental setup and the cell types used.