SARS-CoV-2's exploitation of the EMMPRIN-receptor and potential inhibitors


Senior Member
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 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 (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 abdominal aortic diameter was significantly smaller in the EGCG group than in the control group on day 28(2.960.2 vs 2.360.1 mm;P<.0001). The medial layer wall thickness and elastin content were significantly greater in the EGCG group than in the control group on day 28 (68.4613.6 vs 46.7613.4mm[P<.001] and 20.364.6 vs 9.563.6%[P<.0001], respectively). Gene expression levels of tropoelastin and lysyl oxidase were significantly higher in the EGCG group immediately before AAA induction, indicating promoted elastoregeneration by EGCG administration (tropoe-lastin: 0.5960.36 control vs 1.2460.36 EGCG [P<.05], lysyl oxidase: 0.7760.45 control vs 1.3460.4 EGCG [P<.05])(fold increase). Gene expression levels of inflammatory cytokines, including tumor necrosis factor-a and interleukin-1b, were significantly downregulated in the EGCG group (1.8260.71 vs 0.9760.59 [P<.05] and 3.9163.24 vs 0.8960.59[P<.05], respectively). On day 7, gene expression levels and gelatinolytic activity of matrix metalloproteinase 9 were significantly lower in the EGCG group (1.4160.86 vs 0.5160.42 [P<.05] and 1.0060.17 vs 0.2960.12 [P<.0001],respectively), whereas gene expression levels of tissue inhibitors of metalloproteinase-1 were significantly higher in theEGCG group (0.9660.11 vs 1.1460.09;P<.05).

EGCG attenuated AAA progression in a rat model by preserving the aortic thickness and elastin content of the medial layer through regeneration of elastin, as mediated by anti-inflammatory effects, and subsequent reduction of matrix metalloproteinase activity.
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]:
From the clinical studies reviewed there is no evidence of hepatotoxicity below 800 mg EGCG/day up to 12 months.
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).