Uses of A2 domain of von Willebrand factor
Embodiments of the disclosure encompass methods and compositions for maintaining a healthy fibrin network in an individual. The disclosure includes methods of targeting fibrin in an individual for the purpose of restoring fibrin that is subject to a level of fibrinolysis that is deleterious, such as excessive or reduced with respect to the general population. Such modifications of fibrin in an individual may include direct targeting of fibrin with the A2 domain of von Willebrand factor or a functional derivative or fragment thereof. In specific embodiments, the methods restore to a normal level any imbalance between coagulation and inflammation.
1 . A method of reducing the occurrence, alleviating symptoms, and/or lowering rate of disease progression of a coronavirus infection in an individual, comprising the step of delivering to the individual in need thereof a therapeutically effective amount of a composition comprising an A2 domain of von Willebrand factor, wherein the A2 domain of von Willebrand factor comprises the sequence of SEQ ID NO: 1.
2 . The method of claim 1 , wherein the coronavirus infection comprises severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2) infection.
3 . The method of claim 1 , wherein the individual has severe acute respiratory syndrome (SARS), coronavirus disease 2019 (COVID-19), or a respiratory infection.
4 . The method of claim 1 , wherein the individual has a fever, a cough, shortness of breath, difficulty breathing, tiredness, aches, chills, a sore throat, loss of smell, loss of taste, a headache, diarrhea, vomiting, pneumonia, acute respiratory distress syndrome, organ failure, respiratory failure, a heart condition, acute kidney injury, a viral infection, a bacterial infection, or a combination thereof.
5 . The method of claim 1 , wherein the individual has dysregulated activated coagulation or is at risk for having dysregulated activated coagulation.
6 . The method of claim 1 , wherein the A2 domain interacts directly with a coronavirus.
7 . The method of claim 6 , wherein the interaction prevents infiltration of a coronavirus into a cell of the individual.
8 . The method of claim 1 , wherein the method further comprises administering an effective amount of a second therapy for the coronavirus infection.
9 . The method of claim 8 , wherein the second therapy comprises an antibiotic, an antiviral, convalescent serum, an immune modulator, an anticoagulant, a fluid, oxygen, a corticosteroid, an antibody, GSnP-6, sialyl Lewis X analog, an anti-proliferative, a calcineurin inhibitor, an anti-signaling compound, or a combination thereof.
10 . The method of claim 8 , wherein the second therapy comprises an anti-SARS-CoV-2 drug.
11 . The method of claim 10 , wherein the anti-SARS-CoV-2 drug is selected from the group consisting of azithromycin, AC-55541, apicidin, AZ3451, AZ8838, bafilomycin-A1, CCT 365623, daunorubicin, E-52862, entacapone, GB110, H-89, haloperidol, indomethacin, JQ1, loratadine, merimepodib, metformin, midostaurin, migalastat, mycophenolic-acid, PB28, PD-144418, ponatinib, ribavirin, RS-PPCC, ruxolitinib, RVX-208, S-verapamil, silmitasertib, 4,5,6,7-tetrabromo-2-(dimethylamino)-1H-benzimidazole-1-acetic acid (TMCB), UCPH-101, valproic acid, XL413, ZINC1775962367, ZINC4326719, ZINC4511851, ZINC95559591, 4E2RCat, ABBV-744, camostat, captopril, CB5083, chloramphenicol, chloroquine, hydroxychloroquine, CPI-0610, dabrafenib, DBeQ, dBET6, IHVR-19029, linezolid, lisinopril, minoxidil, ML240, MZ1, nafamostat, pevonedistat, PS3061, rapamycin, sanglifehrin A, sapanisertib, FK-506, ternatin 4, tigecycline, tomivosertib, verdinexor, WDB002, zotatifin, and a combination thereof.
12 . The method of claim 1 , wherein the method further comprises testing for the coronavirus infection.
13 . The method of claim 1 , wherein the delivery of the composition is intravenous, intradermal, transdermal, intrathecal, intraarterial, intraperitoneal, intranasal, intravaginal, intrarectal, topical, intramuscular, subcutaneous, mucosal, oral, and/or local.
14 . The method of claim 1 , wherein the delivery of the composition to the individual occurs multiple times.
15 . The method of claim 14 , wherein the delivery of the composition to the individual occurs once a day, more than once a day, more than once a week, more than once a month, or more than once a year.
16 . The method of claim 1 , wherein the delivery is by constant infusion.
17 . The method of claim 6 , wherein the A2 domain interacts directly with the rod domain of vimentin.
18 . The method of claim 1 , wherein delivery of the composition is by inhalation, by injection, by infusion, via catheter, via lavage, or a combination thereof.
19 . The method of claim 1 , further comprising the step of delivering to the individual in need thereof a therapeutically effective amount of a composition comprising one or more polypeptides comprising the sequence selected from the group consisting of SEQ ID NOs: 2-18, and a combination thereof.