Animal model for SARS-CoV-2-spike induced coagulopathy
Described herein is an animal model useful for identifying therapeutic agents that can inhibit the physiological effects or symptoms of COVID-19 infection, including the effects of the following on one or more organs of the animal: inflammation, oxidative stress, fibrin deposition, blood brain barrier breakdown, clotting, and vascular problems.
1. A method comprising administering virions pseudotyped with SARS-CoV-2 Spike to a rodent and detecting or measuring physiological effects of the SARS-CoV-2 Spike protein on at least one organ of the rodent, wherein human ACE2 receptors are not present.
2. The method of claim 1 , wherein the virions pseudotyped with SARS-CoV-2 Spike are administered repeatedly or continuously to the rodent.
3. The method of claim 1 , further comprising administering a test agent to the rodent.
4. The method of claim 3 , further comprising measuring physiological effects of the SARS-CoV-2 Spike after the test agent is administered.
5. The method of claim 1 , wherein at least one of the organs is a lung, brain, gut, blood vessel, heart, or a combination thereof.
6. The method of claim 3 , wherein the test agent is a small molecule, a polypeptide, or an antibody.
7. The method of claim 6 , wherein the antibody is an anti-fibrin antibody, an anti-fibrinogen antibody, or an anti-SARS-CoV-2 protein antibody.
8. The method of claim 3 , wherein the test agent can bind fibrin or a SARS-CoV-2 protein.
9. The method of claim 1 , wherein the test agent is administered at the same time as the pseudotyped SARS-CoV-2 Spike protein virions, or at a time after the pseudotyped SARS-CoV-2 Spike protein virions are administered.
10. The method of claim 1 , wherein the physiological effects are symptoms of the SARS-CoV-2 infection.
11. The method of claim 1 , wherein the physiological effects comprise inflammation, oxidative stress, fibrin deposition, clots, clot formation, virion binding to fibrin or fibrinogen, SARS-CoV-2 Spike protein binding to fibrin or fibrinogen, Mac-1 protein binding to fibrin or fibrinogen, or a combination thereof.
12. The method of claim 3 , wherein measuring the physiological effects after administering a test agent to the rodent comprises measuring whether the test agent reduces inflammation, oxidative stress, fibrin deposition, clot formation, virion binding to fibrin or fibrinogen, SARS-CoV-2 Spike protein binding to fibrin or fibrinogen, Mac-1 protein binding to fibrin or fibrinogen, or a combination thereof by more than 50% compared to a control.
13. The method of claim 12 , wherein the control is a negative control.
14. The method of claim 1 , wherein the rodent is a mouse, rat, or hamster.