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It seems like the SARS-CoV-2 virus can invade host cells not only via the ACE2 receptor, but also via a receptor called CD147. [1] This receptor is also called "extracellular matrix metalloproteinase inducer" (EMMPRIN) or Basigin. [2] EMMPRIN/CD147 induces the production of matrix metalloproteinases (MMP) such as MMP-9 and MMP-2 [3] [4]. After some research I've found two potential EMMPRIN/CD147 inhibitors:
Doxycycline
Doxycycline reduced the expression of CD147 and inhibited MMP-2 & MMP-9 activity in an in vitro study. [5] Doxycycline have been shown in human trials be a broad-spectrum MMP inhibitor. [6]
EGCG
EGCG (found in green tea) have been shown to inhibit the expression of EMMPRIN and MMP-9 in an in vitro study. [7] In a mouse study intraperitoneally injected EGCG was found to decrease the expression levels of MMP-2, MMP-9, and EMMPRIN. [8] EGCG is notorious for its low bioavailability, which could mean the studies above aren't applicable for normal oral dosages. However, this doesn't seem to be the case.
In a rat study, 20 mg EGCG per day was administered orally in the context of abdominal aortic aneurysm.[9] Rats seems to have the same low absorption of EGCG as humans [10].
The dosage was the equivalent of 0.04 mg EGCG/g body weight/day. If you convert that to a human dose (0,04/6,2[11] = 0,006452mg/g human dose = 6.452 mg/kg human dose) it translates to 452 mg oral EGCG/day for someone who weighs 70kg.
In a human study, breast cancer patients undergoing radiotherapy ingested 400 mg oral EGCG x3 / day for several weeks. The levels of serum active MMP-9 decreased by an average of 31% at week 2 and 55% at week 8. The levels of serum MMP-2 zymogens decreased by an average of 22% at week 2 and 51% at week 8. [12]
The mechanism of action for the reduction of MMP-2 and MMP-9 by EGCG in humans might be via the reduction of EMMPRIN/CD147, but that's just speculation on my part.
EGCG have also been shown to have antifibrotic effects in a human study testing 600 mg oral EGCG/day in patients with pulmonary fibrosis undergoing lung biopsy. [13] This mean that EGCG, apart from potentially having an antiviral effect against the SARS-CoV-2 virus, might reduce the risk of lung scarring from COVID-19.
EGCG doses <800mg/day have not shown any hepatotoxic effects according to the European Food Safety Authority[14]:
An online seller of various nootropic compounds called Nootropics Depot (has a very good reputation when it comes to quality & purity on /r/nootropics) sells a decaffeinated green tea extract containing 45% EGCG for a good price here (10% discount code: REDDITS).
Doxycycline
Doxycycline reduced the expression of CD147 and inhibited MMP-2 & MMP-9 activity in an in vitro study. [5] Doxycycline have been shown in human trials be a broad-spectrum MMP inhibitor. [6]
EGCG
EGCG (found in green tea) have been shown to inhibit the expression of EMMPRIN and MMP-9 in an in vitro study. [7] In a mouse study intraperitoneally injected EGCG was found to decrease the expression levels of MMP-2, MMP-9, and EMMPRIN. [8] EGCG is notorious for its low bioavailability, which could mean the studies above aren't applicable for normal oral dosages. However, this doesn't seem to be the case.
In a rat study, 20 mg EGCG per day was administered orally in the context of abdominal aortic aneurysm.[9] Rats seems to have the same low absorption of EGCG as humans [10].
The dosage was the equivalent of 0.04 mg EGCG/g body weight/day. If you convert that to a human dose (0,04/6,2[11] = 0,006452mg/g human dose = 6.452 mg/kg human dose) it translates to 452 mg oral EGCG/day for someone who weighs 70kg.
In a human study, breast cancer patients undergoing radiotherapy ingested 400 mg oral EGCG x3 / day for several weeks. The levels of serum active MMP-9 decreased by an average of 31% at week 2 and 55% at week 8. The levels of serum MMP-2 zymogens decreased by an average of 22% at week 2 and 51% at week 8. [12]
The mechanism of action for the reduction of MMP-2 and MMP-9 by EGCG in humans might be via the reduction of EMMPRIN/CD147, but that's just speculation on my part.
EGCG have also been shown to have antifibrotic effects in a human study testing 600 mg oral EGCG/day in patients with pulmonary fibrosis undergoing lung biopsy. [13] This mean that EGCG, apart from potentially having an antiviral effect against the SARS-CoV-2 virus, might reduce the risk of lung scarring from COVID-19.
EGCG doses <800mg/day have not shown any hepatotoxic effects according to the European Food Safety Authority[14]:
An online seller of various nootropic compounds called Nootropics Depot (has a very good reputation when it comes to quality & purity on /r/nootropics) sells a decaffeinated green tea extract containing 45% EGCG for a good price here (10% discount code: REDDITS).
